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    Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder. Fusar-Poli Laura,Natale Antimo,Amerio Andrea,Cimpoesu Patriciu,Grimaldi Filioli Pietro,Aguglia Eugenio,Amore Mario,Serafini Gianluca,Aguglia Andrea Brain sciences BACKGROUND:Several inflammatory hypotheses have been suggested to explain the etiopathogenesis of bipolar disorder (BD) and its different phases. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios have been proposed as potential peripheral biomarkers of mood episodes. METHODS:We recruited 294 patients affected by BD, of which 143 were experiencing a (hypo)manic episode and 151 were in a depressive phase. A blood sample was drawn to perform a complete blood count. NLR, PLR, and MLR were subsequently calculated. A -test was performed to evaluate differences in blood cell counts between depressed and (hypo)manic patients and a regression model was then computed. RESULTS:Mean values of neutrophils, platelets, mean platelet volume, NLR, PLR, and MLR were significantly higher in (hypo)manic than depressed individuals. Logistic regression showed that PLR may represent an independent predictor of (hypo)mania. CONCLUSIONS:Altered inflammatory indexes, particularly PLR, may explain the onset and recurrence of (hypo)manic episodes in patients with BD. As inflammatory ratios represent economical and accessible markers of inflammation, further studies should be implemented to better elucidate their role as peripheral biomarkers of BD mood episodes. 10.3390/brainsci11010058
    Prevalence and risk factors for non-suicidal self-injury among patients with depression or bipolar disorder in China. Wang Lu,Liu Jun,Yang Yuan,Zou Haiou BMC psychiatry BACKGROUNDS:Non-suicidal self-injury is a serious health problem among patients with depression or bipolar disorder. However, few studies within the Chinese context have investigated the prevalence of NSSI and its risk factors in above populations. The purpose of this study was to investigate the prevalence of non-suicidal self-injury and its risk factors in patients with depression or bipolar disorder in China. METHODS:The final sample comprised of 394 inpatients(M = 29.71; SD = 11.95) with depression or bipolar disorder from two psychiatric hospitals in Beijing, China. A General Demographic Data Form, the Non-suicidal Self-injury Questionnaire(NSSI-Q), Impulsivity Item and the Adverse Childhood Experiences-International Questionnaire(ACE-IQ) were completed by all patients. RESULTS:Of the 394 patients examined, 245(62.2%) of this sample reported NSSI in past year. Of the 245 patients with NSSI, 135(55.1%) were diagnosed with depression and 110(44.9%) were diagnosed with bipolar disorder. The most common methods of NSSI for female was "pinching"(23.1%) and "scratching"(22.8%), while for male it was "hiting hard objects"(12.7%). By multivariate regression analysis, young age, unemployment, a higher monthly family income, single, impulsivity, long duration of illness and ACEs were risk factors for NSSI in patients with depression and bipolar disorder(P<0.05). CONCLUSIONS:Our study points to the fact that there was an unfortunate message about the prevalence of NSSI among patients with depression or bipolar disorder in China. It is necessary not only to raise the awareness of NSSI in families and society, but also to formulate targeted assessment and intervention. Moreover, future research should not only focus on individuals being hospitalized, but should be representative of individuals treated at home or in the community because there are no national statistics on NSSI among such patients in China. 10.1186/s12888-021-03392-y
    Bipolar depression and suicidal ideation: Moderators and mediators of a complex relationship. Kamali Masoud,Reilly-Harrington Noreen A,Chang Weilynn C,McInnis Melvin,McElroy Susan L,Ketter Terence A,Shelton Richard C,Deckersbach Thilo,Tohen Mauricio,Kocsis James H,Calabrese Joseph R,Gao Keming,Thase Michael E,Bowden Charles L,Kinrys Gustavo,Bobo William V,Brody Benjamin D,Sylvia Louisa G,Rabideau Dustin J,Nierenberg Andrew A Journal of affective disorders INTRODUCTION:Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. METHODS:482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. RESULTS:Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. LIMITATIONS:Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. DISCUSSION:Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions. 10.1016/j.jad.2019.08.032
    Metabolomic analysis to detect urinary molecular changes associated with bipolar depression. Ren Yan,Chen Zhen-Zhu,Sun Xiao-Li,Duan Hui-Jun,Tian Jun-Sheng,Wang Jia-Ying,Yang Hong Neuroscience letters Bipolar disorder (BD) is a debilitating mental disorder with complex clinical manifestations and low diagnostic accuracy. Depressive episodes are most common in the course of BD with high comorbidity and suicide rates, which present greater clinical challenges than mania and hypomania episodes. However, there are no objective biomarkers for bipolar depression. The aim of this study was to detect urinary metabolite biomarkers that could be useful for the diagnosis of bipolar depression. Nuclear magnetic resonance spectroscopy was used to profile urine samples of patients with bipolar depression (n = 37) and healthy volunteers (n = 48). Data were analyzed using Orthogonal Partial Least Square Discriminant Analysis and t-test. Differential metabolites were identified (VIP > 1 and p < 0.05), and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways. In total, we identified seven metabolites differentially expressed in patients with BD and healthy controls. Compared with healthy group, the levels of betaine, glycerol, hippuric acid, indole sulfate, trimethylamine oxide, and urea in urine samples of BD patients were significantly higher, while the level of inositol was significantly lower. Most of these small molecules are related to lipid metabolism and gut microbiota metabolism. These differential metabolites could provide critical insight into the pathological mechanisms of bipolar depression. The results of this study provide a meaningful reference for similar and further studies in the future. 10.1016/j.neulet.2020.135515
    Bipolar Disorder and Suicide: a Review. Miller Jacob N,Black Donald W Current psychiatry reports PURPOSE OF REVIEW:Bipolar disorder has the highest rate of suicide of all psychiatric conditions and is approximately 20-30 times that of the general population. The purpose of this review is to discuss findings relevant to bipolar disorder and suicide. RECENT FINDINGS:Risk factors include male gender, living alone, divorced, no children, Caucasian, younger age (< 35 years), elderly age (> 75 years), unemployment, and a personal history of suicide attempt and family history of suicide attempt or suicide completion, as well as predominant depressive polarity. Suicide is associated with the depressed or mixed subtypes, not mania. Although there are emerging treatments for bipolar depression, such as ketamine and TMS, lithium remains the only medication associated with lowered suicide rates in bipolar disorder. Understanding clinical and demographic risk factors for suicide in bipolar disorder remains the best way to prevent suicidal behavior. Early intervention and treatment with anti-suicidal medications, such as lithium, along with close observation and follow-up is the best way to mitigate suicide in patients with bipolar disorder. 10.1007/s11920-020-1130-0
    Suicidality in patients with bipolar depression: Findings from a lower middle-income country. Journal of affective disorders The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression. 10.1016/j.jad.2021.04.015
    Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial. JAMA psychiatry Importance:Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective:To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants:This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions:Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures:Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results:The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance:In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration:ClinicalTrials.gov Identifier: NCT01928446. 10.1001/jamapsychiatry.2021.3170
    Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammatory Index in Different States of Bipolar Disorder. Brain sciences The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We conducted a case-control study recruiting 180 BD patients and 407 healthy controls. BD patients who met the inclusion criteria and were hospitalized due to BD at the psychiatry clinic of the University General Hospital of Larisa, Greece, until September 2021 were included in the study. Among them, 111 patients experienced a manic episode and 69 patients experienced a depressive episode. Data including a complete blood count were retrieved from their first admission to the hospital. Bipolar patients had a higher NLR, MLR and SII index compared to healthy controls when they were experiencing a manic episode ( &lt; 0.001) and a depressive episode ( &lt; 0.001). MLR was increased with large effect size only in patients expressing manic episodes. Neutrophils and NLR had the highest area under the curve with a cutoff of 4.38 and 2.15 in the ROC curve, respectively. Gender-related differences were mainly observed in the SII index, with males who were expressing manic episodes and females expressing depressive episodes having an increased index compared to healthy controls. The NLR, MLR and SII index were significantly higher in patients with BD than in healthy controls, which implies a higher grade of inflammation in BD patients. 10.3390/brainsci12081034
    Neutrophil-lymphocyte and platelet-lymphocyte ratios as inflammation markers for bipolar disorder. Kalelioglu Tevfik,Akkus Mustafa,Karamustafalioglu Nesrin,Genc Abdullah,Genc Esra Sena,Cansiz Alparslan,Emul Murat Psychiatry research In the present study we investigated the involvement of inflammatory cells and their ratios as inflammation markers in Bipolar Disorder. We have enrolled 61 manic, 55 euthymic patients and 54 control subjects to the study. Neutrophil-lymphocyte and platelet-lymphocyte ratios were found significantly higher in both manic and euthymic patients compared to control group. These findings suggest that the inflammatory cells have a role in the pathophysiology of bipolar disorder manic and even in euthymic state. 10.1016/j.psychres.2015.05.110
    Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with bipolar disorder: A preliminary study. Cevher Binici Nagihan,Alşen Güney Sevay,İnal Emiroğlu F Neslihan Psychiatry research We aimed to evaluate the neutrophil lymphocyte and platelet lymphocyte ratios among euthymic adolescents with bipolar disorder (BD) type I. Thirty-six adolescents with BD and 30 healthy controls were included in the study. The diagnosis was made by experienced physicians using the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the affective module of Washington University in St. Louis Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia-Present State and Lifetime. Blood samples were taken during euthymia, which was defined as Young Mania Rating Scale and Hamilton Depression Rating Scale scores below 7. There was no significant difference in neutrophil lymphocyte ratio and platelet lymphocyte ratio between the patient and control group. Considering the literature, we may speculate that in the early stages, euthymia is associated with a lower inflammatory response, and prolongation of BD causes increased inflammatory processes predominant even in euthymia. In pediatric BD, further studies that assess neutrophil lymphocyte ratio and platelet lymphocyte ratio during different mood episodes and that identify neutrophil lymphocyte ratio and platelet lymphocyte ratio changes during the course of the disease will clarify the role of inflammation in the etiology of pediatric BD. 10.1016/j.psychres.2018.08.065
    Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode. Dos Santos Oliveira Pedro Miguel,Santos Vítor,Coroa Manuel,Ribeiro Joana,Madeira Nuno Bipolar disorders OBJECTIVES:There are no well-established biomarkers to predict the risk of conversion to bipolar disorder (BD) in patients with depression. Given the putative role of purinergic neurotransmission dysfunction in BD, the purpose of our study was to evaluate if higher serum uric acid (UA) levels could predict BD conversion in depressed inpatients. METHODS:We reviewed retrospectively the records of subjects hospitalized between June 2007 and June 2010 with a diagnosis of major depressive disorder (MDD) who had undergone routine UA levels testing at admission. At an approximate 10-year follow-up we identified subjects with a subsequent diagnosis of BD. We compared UA levels between the BD-converter and non-BD converter groups, performed Receiver operating characteristic curve analysis to evaluate the prognostic accuracy of serum UA levels and calculated the clinical utility index (CUI) as a risk biomarker for conversion to BD. RESULTS:The study included 250 subjects (55 "BD-converters" and 195 "No BD-converters"). "BD-converters" had significantly higher plasma UA levels compared to "No BD-converters" in their index hospitalization irrespective of gender (males: 403.84 ± 91.76 vs 270.81 ± 53.58 µmol/L; U = 94.5, P < 0.001 and females 302.19 ± 52.64 vs 202.69 ± 48.93 µmol/L; t = 10.75, P < 0.001). Serum UA levels showed a very good to excellent accuracy for predicting conversion to BD in inpatients with MDD (area under the curve [AUC]: 0.90; 95% CI: 0.86, 0.94) and had a good to excellent CUI- and a moderate to good CUI+ grading for discriminating BD-converter cases from non-BD converters. CONCLUSIONS:Our study suggests that depressed patients with higher levels of serum UA are at greater risk of a subsequent manic or hypomanic episode. The purinergic system could prove a promising path for the search of biomarkers in BD. 10.1111/bdi.12708
    Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort. Journal of affective disorders BACKGROUND:The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort. METHOD & RESULTS:We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning. CONCLUSIONS:The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health. 10.1016/j.jad.2022.03.053
    The association between childhood trauma and the age of onset in drug-free bipolar depression. Psychiatry research OBJECTIVE:This study aimed to investigate the relationship between childhood trauma and clinical correlates in bipolar depression. METHODS:A total of 61 bipolar depression patients were enrolled and assessed based on the Childhood Trauma Questionnaire-Short Form (CTQ-SF), Patient Health Questionaire-15 (PHQ-15), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) systems. RESULTS:The age of onset in bipolar depression patients with either trauma or abuse or neglect was significantly lower than in patients without these factors. There were statistically significant negative correlations between the age of onset and the number of different trauma types in bipolar depression patients. Multiple variable regression showed a significant association between the number of trauma types and the age of onset. Furthermore, there was a significant negative correlation between the age of onset with CTQ-SF total score (CTS), emotional abuse score and emotional neglect score, and physical neglect score. However, multiple variable regression analysis revealed that there was a significant association between emotional abuse score and the age of onset of bipolar depression patients. CONCLUSION:Our results suggest that childhood trauma may be associated with physical symptoms and the age of onset in bipolar depression patients. 10.1016/j.psychres.2022.114469
    Body mass index and blood pressure in bipolar patients: Target cardiometabolic markers for clinical practice. Cuellar-Barboza Alfredo B,Cabello-Arreola Alejandra,Winham Stacey J,Colby Colin,Romo-Nava Francisco,Nunez Nicolas A,Morgan Robert J,Gupta Ruchi,Bublitz Joshua T,Prieto Miguel L,De Filippis Elena A,Lopez-Jimenez Francisco,McElroy Susan L,Biernacka Joanna M,Frye Mark A,Veldic Marin Journal of affective disorders OBJECTIVE:To evaluate the association between cardiometabolic markers and bipolar disorder (BD), examining the impact of sex and cardiometabolic medication use, from a large case-control biorepository of more than 1300 participants. PATIENTS AND METHODS:Recruited from July 2009 through September 2017, cardiometabolic markers were harvested from electronic health records (EHR) of participants (n=661) from the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder and Mayo Clinic Biobank age-sex-matched controls (n=706). Markers were compared between cases and controls using logistic regression, stratified by sex, adjusting for cardiometabolic medications and current smoking status. We studied the effect of psychotropics in case-only analyses. RESULTS:The mean age of the sample was 52.5 ± 11.6 years and 55% were female. BD patients had higher rates of smoking, but lower utilization of lipid-lowering medication compared with controls. After adjustment, BD was associated with obesity [Odds ratio (CI) 1.62 (1.22-2.15)], elevated systolic blood pressure (SBP) [2.18 (1.55-3.06)] and elevated triglycerides [1.58 (1.13-2.2)]. When stratified by sex, obesity [1.8 (1.23-2.66)] and systolic blood pressure [2.32 (1.46-3.7)] were associated with BD females compared to female controls; however, only systolic blood pressure [2.04 (1.23-3.42)] was associated with male bipolars compared to male controls. Psychotropics were marginally associated with mean BMI, abnormal triglycerides, and HbA1c. LIMITATIONS:EHR cross-sectional data CONCLUSION: To our knowledge, this is the largest case controlled study to date to explore the association between cardiometabolic markers and bipolar disorder adjusting for utilization of cardiometabolic medication. Identification of significant, non-laboratory based cardiometabolic markers that are associated with increased risk of major cardiovascular adverse events in patients with bipolar disorder, underscores, both the utility and importance of risk monitoring that can be easily done in community mental health centers. 10.1016/j.jad.2020.12.121
    Symptoms of mania and anxiety do not contribute to suicidal ideation or behavior in the presence of bipolar depression. Persons Jane E,Lodder Paul,Coryell William H,Nurnberger John I,Fiedorowicz Jess G Psychiatry research Bipolar disorder is typified by episodes of manic/hypomanic and depressive symptoms, either distinctly or concurrently as mixed symptoms. While depressive symptoms are the major driver of risk, it is unclear whether specific combinations of manic and anxiety symptoms contribute differentially to suicidal ideation and behavior in individuals with bipolar disorder during a depressive state. This study uses a quantitative application of Rothman's theoretical framework of causation, or 'causal pies' model. Data were obtained from the National Network of Depression Centers Mood Outcomes Program for 1028 visits from 626 individuals with bipolar disorder with current moderate-to-severe depressive symptoms, operationalized as a Patient Health Questionnaire-8 (PHQ-8) score ≥10. Mania symptoms were captured using the Altman Self-Rating Mania scale (ASRM) and anxiety symptoms were captured using the Generalized Anxiety Disorder-7 scale (GAD-7). The outcome of suicidal ideation or behavior was captured using the Columbia Suicide Severity Rating Scale (C-SSRS). In this cohort of individuals with bipolar disorder and at least moderate depressive symptoms, we found no increased risk of suicidal ideation or behavior attributable to manic and anxiety symptom clusters in individuals with bipolar disorder during depressive state. A small amount (4%) of risk was attributable to having severe depressive symptoms. These findings, however, may be influenced by limitations in sample size and measurement instruments. Future studies would benefit from larger samples and more rigorous assessments, including clinician-rated measures. 10.1016/j.psychres.2021.114296
    Decreased serum zinc concentration during depressive episode in patients with bipolar disorder. Siwek Marcin,Sowa-Kućma Magdalena,Styczeń Krzysztof,Szewczyk Bernadeta,Reczyński Witold,Misztak Paulina,Topór-Mądry Roman,Nowak Gabriel,Dudek Dominika,Rybakowski Janusz K Journal of affective disorders OBJECTIVES:Zinc may be involved in the pathophysiology and treatment of depressive disorder. However, data on this issue in bipolar disorder (BD) are limited. The aim of the study was to assess zinc concentrations in the blood serum of patients at various phases and stages of bipolar disorder. METHODS:The study included 129 patients with a diagnosis of bipolar disorder type I (n=69) or type II (n=60). Fifty-eight were in a depressive episode, 23 in a manic episode and 48 in remission. Fifty healthy volunteers made a control group. Zinc concentration was measured using flame atomic absorption spectrometry. RESULTS:Serum zinc level in patients diagnosed with BD type I in the depressive phase was significantly reduced as compared with mania, remission and healthy subjects. In the BD type II, serum zinc level in hypomania, depression or remission phase was not significantly different from the control group. In the whole group, lower level of zinc in depression compared to remission and control subjects was found during late stage of the illness but not in the early stage. Zinc concentration was not dependent on the severity of manic or depressive symptoms and subtype of depression but correlated positively with the number of manic/hypomanic relapses in the past year. LIMITATIONS:Lack of prospective model, heterogeneity of pharmacological treatment, small number of subgroups presenting specified clinical features. CONCLUSIONS:Decreased serum zinc concentration occurs in depression in BD type I and probably in depression in the late stage of BD. 10.1016/j.jad.2015.10.026
    Clinical staging in bipolar disorder: focus on cognition and functioning. Rosa Adriane R,Magalhães Pedro V S,Czepielewski Letícia,Sulzbach Miréia Viana,Goi Pedro D,Vieta Eduard,Gama Clarissa S,Kapczinski Flávio The Journal of clinical psychiatry OBJECTIVE:Clinical staging has increasingly been considered suitable for psychiatric disorders such as bipolar disorder. A staging model of bipolar disorder could help clinicians understand the mechanisms underlying the course of the illness and guide prognosis and therapy. This study aimed to investigate differences in functional status and cognitive functioning in patients in different clinical stages of bipolar disorder. METHOD:Subjects who met DSM-IV criteria for bipolar disorder (n = 54) were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre (Brazil) from October 2012 to October 2013. All patients had been in remission (score < 7 on the 17-item HDRS and the YMRS) for at least 1 month before assessment. They were classified into 4 clinical stages according to the model described by Kapczinski et al and compared to 43 healthy controls. Functional status was assessed by using the Functioning Assessment Short Test (FAST). Neuropsychological measures were performed to investigate cognitive functioning. RESULTS:Significant differences in functional status were found between patients in all stages compared to controls (F = 33.014, P < .001), except for stage I (P = .104). Additionally, a very strong linear association was found between FAST scores and clinical stages, with FAST scores increasing from stage I to IV (F = 149.55, P < .001). In the bipolar group, stage I was associated with better occupational functioning than stage II (F = 48.344, P = .003). Stage IV patients experienced greater impairment in autonomy than stage III patients (F = 26.646, P = .004), and stage III patients experienced poorer autonomy than those in stage II (P = .004). With regard to cognitive measures, patients in late stages (stages III and IV) were more impaired than healthy controls (P < .001). A similar performance was found between patients in early stages (stages I and II) and healthy controls. DISCUSSION:This study showed progressive functional changes from stage I to stage IV of bipolar disorder, with a greater impairment in patients in later stages of the illness. FAST scores seem to have a good discriminant ability to distinguish between patients in early versus late stages of bipolar disorder and could therefore contribute to the development of a bipolar disorder staging system. 10.4088/JCP.13m08625
    Sleep alterations in pediatric bipolar disorder versus attention deficit disorder. Estrada-Prat Xavier,Álvarez-Guerrico Ion,Batlle-Vila Santiago,Camprodon-Rosanas Ester,Martín-López Luís Miguel,Álvarez Enric,Romero Soledad,Elices Matilde,Pérez Víctor Psychiatry research Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) share numerous clinical features, which can make the differential diagnosis challenging. Studies conducted in adults suggest that patients with BD and ADHD have different sleep patterns. However, in pediatric populations, data on these potential differences are scant. The present preliminary study was conducted to identify potential differences in sleep alterations among youths diagnosed with BD or ADHD compared to healthy controls (HC). A total of 26 patients diagnosed with BD (n = 13) or ADHD (n = 13) were compared to 26 sex- and age-matched HC ([HC], n = 13, and [HC], n = 13). All participants underwent polysomnography. The mean duration of stage N2 sleep was shorter in the BD group than in controls (HC). The BD group also had higher (non-significant) REM density (REMd) scores than controls while mean REMd scores were lower in the ADHD group versus controls. Compared to the ADHD group, the BD group presented a shorter N2 stage, a longer first REM sleep duration (R1), and greater REMd. According to our findings, these three variables-N2 stage, REMd, and R1-appear to differentiate patients with BD from those with ADHD and from HC. 10.1016/j.psychres.2019.01.108
    The differential association between history of childhood sexual abuse and body mass index in early and late stages of bipolar disorder. Leclerc Emilie,Mansur Rodrigo B,Grassi-Oliveira Rodrigo,Cordeiro Quirino,Kapczinski Flavio,McIntyre Roger S,Brietzke Elisa Journal of affective disorders BACKGROUND:History of distal stressors such as childhood trauma is a well-established, non-specific vulnerability factor for multiple mental illnesses. The objective of this study was to investigate the possible association between history of childhood trauma and body mass index (BMI) in individuals in early and late stages of bipolar disorder (BD) and to verify is there was any difference in the association of sexual abuse history and obesity in early versus late stages of BD. METHODS:Seventy-one euthymic BD-type I patients and eighty-one healthy controls were evaluated using the Childhood Trauma Questionnaire (CTQ) and body mass index (BMI). The association between BMI and CTQ total and subscores were evaluated dividing BD population in early-stage BD-I (less than 10 years since onset of disease) or late-stage BD (more than 10 years). RESULTS:BD individuals had higher rates of history of childhood trauma than HC, especially sexual and emotional abuse, after adjusting for confounders. We observed a moderating effect of group on the association between BMI and sexual abuse (SA), but not on other modalities of childhood trauma, after adjustments for age, gender, ethnicity, education, alcohol and tobacco use. LIMITATIONS:Our sample included a predominance of female individuals. The study cross-sectional design does not allow concluding a cause-effect relationship. In dividing the BD subgroups in relation with the time since the onset, we supposed that the natural course of BD is linear. The CTQ is subject to recall bias. CONCLUSION:There is a relationship between childhood sexual abuse and BMI, but the direction of the association varies across the different stages of BD-I. 10.1016/j.jad.2017.10.031
    Repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder: A systematic review. Bipolar disorders OBJECTIVES:Repetitive transcranial magnetic stimulation (rTMS) is commonly used in unipolar depression; yet, its evidence in bipolar disorder (BD) is limited. We sought to review the evidence on the use of rTMS across the different stages of BD. METHODS:MEDLINE database was systematically searched using the PubMed interface following the PRISMA guidelines. Inclusion criteria were as follows: (i) randomized clinical trials (RCTs), open-label studies, and case series; (ii) specific evaluation of the treatment outcomes using psychometric scales; (iii) clinical studies in adults; and (iv) articles in the English language. The systematic review has been registered on PROSPERO (CRD42020192788). RESULTS:Thirty-one papers were included in the review. Most studies included participants diagnosed with a bipolar depressive episode (N = 24), have yielded mixed findings, and have yet to reach a consensus on the most effective rTMS protocol. Few studies examined the effect of rTMS during manic (N = 5) or mixed episode (N = 1), or as maintenance treatment (N = 1). The limited data thus far suggest rTMS to be relatively safe and well tolerated. Small sample sizes, heterogeneity among study designs, patients and control groups recruited, rTMS parameters, and outcome measures are among the most significant limitations to these studies. CONCLUSION:The current data regarding the application of rTMS in BD patients remain limited. More adequately powered sham-controlled studies are required to verify its efficacy. Large-scale clinical trials are needed to also determine whether its effects extend to manic and mixed episodes, as well as its role in mood stabilization and amelioration of suicidal behavior. 10.1111/bdi.13099
    Sleep alterations in individuals recently diagnosed with bipolar disorder across different mood stages. Vieira Igor Soares,Barreto Nathalia Tessele,Pedrotti Moreira Fernanda,Mondin Thaise Campos,Simjanoski Mario,Cardoso Taiane de Azevedo,Kapczinski Flávio,Jansen Karen,Souza Luciano Dias de Mattos,da Silva Ricardo Azevedo Psychiatry research OBJECTIVES:To assess the differences in sleep impairments in major depressive disorder (MDD) and individuals recently diagnosed with bipolar disorder (BD) across different mood stages. METHODS:This is a cross-sectional study corresponding to the second wave of a prospective clinical cohort of a sample of outpatients. The first wave included subjects diagnosed with MDD aged 18 to 60 years. Averaging 3 years after the first phase (second wave), conversion from MDD to BD diagnosis was assessed using the Mini International Neuropsychiatric Interview. The total sample was divided into four groups: euthymic MDD, MDD in a current episode, euthymic BD, and BD in a current mood episode. The sleep alterations were assessed using the Pittsburgh Sleep Quality Index. RESULTS:The sample included 468 subjects (261 euthymic MDD, 149 MDD currently depressed, 16 euthymic BD, and 42 BDs currently in a (hypo)manic or depressive episode). Euthymic BD differed from euthymic MDD only in the domains of sleep efficiency and sleep disturbances, showing lower sleep efficiency (PR 4.91 [95%CI 1.94 - 12.42]) and higher sleep disturbances (PR 3.38 [95%CI 1.32 - 8.67]) in subjects recently diagnosed with BD during euthymia. These differences remained significant after adjusting for the potential confounding factors. CONCLUSIONS:The findings point out the relevance of regular sleep assessments in individuals recently diagnosed with BD, since the differences in sleep quality observed could provide insights regarding prognosis, treatment, and the extent to which these individuals display significant subsyndromal symptomatology, even in the absence of a mood episode. 10.1016/j.psychres.2021.113824
    Relationship of free thyroxine and triiodothyronine on recurrence in maintenance therapy for bipolar depression. Asian journal of psychiatry OBJECTIVE:To examine whether thyroid function in the normal range is associated with recurrence of depressive or mania in bipolar disorder patients. METHODS:104 patients with bipolar disorder in maintenance therapy phase were assigned randomly to mood stabilizer combined with antidepressant group or mood stabilizer group. There were 52 patients in both groups respectively. Clinical symptoms were assessed at baseline, 3rd month, 6th month, 9th month, and 12th month using HAMD-17 and YMRS. Blood samples were analyzed for thyroid function. RESULTS:There was no statistically significant difference of recurrence rate of depressive episode and mania episode at the end of the 12-months between mood stabilizer combined with antidepressant group and mood stabilizer group. There was significant relation of baseline TT4 (P = 0.020, HR = 0.948), FT3 (P = 0.035, HR = 2.055), and FT4 (P = 0.047, OR=0.769) with the recurrence of depressive episode in mood stabilizer group. The area under curve (AUC) of TT4, FT3, FT4 were 0.685, 0.613, 0.544, respectively. There was significant relation of baseline FT3 (P = 0.044,HR = 4.493) with the recurrence of mania episode for mood stabilizer combined with antidepressants group. The AUC of FT3 was 0.806. CONCLUSION:Low level of TT4, FT4 and high level of FT3 within normal-range were related with the recurrence of depressive episode in the maintenance treatment with mood stabilizer of bipolar disorder. High level of FT3 within normal-range were related with recurrence of mania when mood stabilizer combined with antidepressants were used in the maintenance treatment of bipolar disorder. 10.1016/j.ajp.2022.103086
    Prevalence of metabolic syndrome and its clinical correlates among patients with bipolar disorder. Kumar Ajay,Narayanaswamy Janardhanan C,Venkatasubramanian G,Raguram R,Grover Sandeep,Aswath Manju Asian journal of psychiatry OBJECTIVE:To assess the prevalence of metabolic syndrome (MetS) in patients with bipolar disorder (BD) and examine the clinical correlates of MetS. METHODS:Sixty-seven patients with BD were evaluated for presence for MetS. The consensus definition was used to define MetS. The clinical variables were recorded on the basis of information provided by the patients, accompanying caregivers and review of treatment records. The symptoms severity of present depressive and manic episode was assessed by using Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) respectively. RESULTS:The prevalence of MetS was 53.7%. Patients with MetS were older than the patients with BD alone (P=0.001). Increased waist circumference was the most common abnormal parameter (74.6%) followed by low high density lipoprotein (HDL) (71.6%) and raised triglycerides (64.2%). High blood pressures were recorded in 35.8% with high fasting blood glucose levels were seen in 33.3%. MetS was associated with greater number of life time episodes (p=0.010), longer duration of illness (p=0.010), greater numbers of lifetime depressive episodes (p<0.001). Substance use (alcohol and nicotine) associated with significantly higher prevalence of high blood pressure among MetS patients (p<0.001) while abnormal triglyceride level shown associated with substance use (p=0.010). Age of the patients, number of lifetime depressive episodes and use of Olanzapine were found to predictive of the development of MetS. CONCLUSIONS:Patients with BD have high prevalence of MetS and its presence correlates with clinical variables. 10.1016/j.ajp.2017.01.020
    Cumulative Cardiovascular Disease Risk and Triglycerides Differentially Relate to Subdomains of Executive Function in Bipolar Disorder; preliminary findings. Van Rheenen Tamsyn E,McIntyre Roger S,Balanzá-Martínez Vicent,Berk Michael,Rossell Susan L Journal of affective disorders OBJECTIVES:Cardiovascular disease is disproportionally prevalent in bipolar disorder (BD) and has been linked to cognition in preliminary studies. Herein we evaluate the association between known risk factors for cardiovascular disease and executive function in BD patients compared to healthy controls. METHODS:In a sample of n=57 individuals (n=23 BD, n=34 controls) we assessed two subdomains of executive function; cognitive flexibility (using the Trail Making Test - Part B) and cognitive inhibition (using the Stroop Colour Word Interference Task). Cardiovascular risk was assessed by means of serum triglyceride levels, body mass index (BMI) and waist circumference, as well as dietary saturated fat intake and a sex-specific cumulative cardiovascular risk score calculated using the Framingham Heart Study method. RESULTS:Patients with BD had higher BMI and waist circumference, with more BD patients categorized as having central obesity than controls. In the BD group only, higher triglyceride levels were associated with worse cognitive flexibility, and elevated cumulative cardiovascular disease risk was associated with worse cognitive inhibition. No correlations between cardiovascular risk factors and executive function were evident in the control group. LIMITATIONS:The study was limited by the small sample size and should be considered hypothesis-generating CONCLUSIONS: The associations between triglyceride levels, cumulative cardiovascular disease risk and executive functioning evident in BD in this study preliminarily indicate the potential for mechanistic overlap of physical health and cognitive function in the disorder. 10.1016/j.jad.2020.09.104
    High Prevalence of Metabolic Syndrome Among Adolescents and Young Adults With Bipolar Disorder. Li Christine,Birmaher Boris,Rooks Brian,Gill Mary Kay,Hower Heather,Axelson David A,Dickstein Daniel P,Goldstein Tina R,Liao Fangzi,Yen Shirley,Hunt Jeffrey,Iyengar Satish,Ryan Neal D,Strober Michael A,Keller Martin B,Goldstein Benjamin I The Journal of clinical psychiatry OBJECTIVE:Despite abundant literature demonstrating increased metabolic syndrome (MetS) prevalence and important clinical correlates of MetS among middle-age adults with bipolar disorder, little is known about this topic among adolescents and young adults early in their course of bipolar disorder. We therefore examined this topic in the Course and Outcome of Bipolar Youth (COBY) study. METHODS:A cross-sectional, retrospective study was conducted of 162 adolescents and young adults (mean ± SD age = 20.8 ± 3.7 years; range, 13.6-28.3 years) with bipolar disorder (I, II, or not otherwise specified, based on DSM-IV) enrolled in COBY between 2000 and 2006. MetS measures (blood pressure, glucose, high-density lipoprotein cholesterol [HDL-C], triglycerides, and waist circumference), defined using the International Diabetes Federation criteria, were obtained at a single timepoint. Mood, comorbidity, and treatment over the 6 months preceding the MetS assessment were evaluated using the Longitudinal Interval Follow-Up Evaluation. RESULTS:The prevalence of MetS in the sample was 19.8% (32/162). Low HDL-C (56.5%) and abdominal obesity (46.9%) were the most common MetS criteria. MetS was nominally associated with lower lifetime global functioning at COBY intake (odds ratio [OR] = 0.97, P = .06). MetS was significantly associated with percentage of weeks in full-threshold pure depression (OR = 1.07, P = .02) and percentage of weeks receiving antidepressant medications (OR = 1.06, P = .001) in the preceding 6 months. MetS was not associated with manic symptoms or medications other than antidepressants. CONCLUSIONS:The prevalence of MetS in this sample was at least double compared to the general population. Moreover, MetS is associated with increased burden of depression symptoms in this group. Management of early-onset bipolar disorder should integrate strategies focused on modifying MetS risk factors. 10.4088/JCP.18m12422
    Elevated triglycerides are associated with decreased executive function among adolescents with bipolar disorder. Naiberg M R,Newton D F,Collins J E,Dickstein D P,Bowie C R,Goldstein B I Acta psychiatrica Scandinavica OBJECTIVE:Cardiovascular risk factors that comprise metabolic syndrome (MetS) have been linked with cognition in adults with bipolar disorder (BD). This study examines the association between MetS components and executive function in adolescents with BD. METHODS:A total of 34 adolescents with BD and 35 healthy control (HC) adolescents were enrolled. MetS components included triglycerides, high-density lipoprotein, glucose, waist circumference, and systolic and diastolic blood pressure. Executive functioning was measured using the intra-extra-dimensional (IED) set-shifting task from the Cambridge Neuropsychological Tests Automated Battery. RESULTS:Adolescents with BD were more likely to have ≥1 MetS components (64.7%) as compared to HC participants (22.9%, χ(2) = 12.29, P = <0.001). Adolescents with BD also had poorer IED task performance compared to HC adolescents (composite Z-score: 0.21 ± 0.52 vs. 0.49 ± 0.51, P = 0.011). Within the BD group, IED composite Z-scores were correlated with diastolic blood pressure and triglyceride levels (ρ = -0.358, P = 0.041 and ρ = -0.396, P = 0.020 respectively). The association of triglycerides with executive function remained significant after controlling for age, IQ, and current use of second-generation antipsychotics. CONCLUSION:Elevated triglycerides are associated with poorer executive function among adolescents with BD. Studies of behavioural and pharmacological interventions targeting MetS components for the purpose of improving executive function among adolescents with BD are warranted. 10.1111/acps.12603
    Comparison of blood lipid profile/thyroid function markers between unipolar and bipolar depressed patients and in depressed patients with anhedonia or suicidal thoughts. Su Meilei,Li Enze,Tang Chong,Zhao Yongzhi,Liu Ruqing,Gao Keming Molecular medicine (Cambridge, Mass.) BACKGROUND:This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. METHODS:A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. RESULTS:The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. CONCLUSION:Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups. 10.1186/s10020-019-0119-9
    Association between abnormal glycolipid level and cognitive dysfunction in drug-naïve patients with bipolar disorder. Qiu Yan,Li Sujuan,Teng Ziwei,Tan Yuxi,Xu Xuelei,Yang Min,Zhao Ziru,Liu Jieyu,Tang Hui,Xiang Hui,Chen Jindong,Wang Bolun,Wu Haishan Journal of affective disorders OBJECTIVES:Cognitive impairment and abnormal glycolipid metabolism are common clinical features of bipolar disorder (BD). The purpose of this study was to investigate the relationship between conventional glycolipid metabolism indicators and cognitive impairment in patients with BD. METHODS:A total of 132 drug-naïve patients with BD and 129 healthy controls (HC) were recruited in the study. Five serum glycolipid metabolism indicators were measured and cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test) for each participant. RESULTS:The scores of immediate memory, attention, language and delayed memory in BD group were significantly lower than those in HC group (P < 0.05). The triglyceride (TG) level in BD group was higher than that in HC group (P = 0.011), and the total cholesterol and high-density lipoprotein cholesterol (HDL) levels were lower than those in HC group (P = 0.026; P = 0.001). Regression analysis showed that TG level was significantly correlated with RBANS total score (β = 0.245, P = 0.008), attention (β = 0.289, P = 0.03) and delayed memory (β = 0.221, P = 0.023). Fasting blood glucose (FBG) level was significantly correlated with language subscale score (β = -0.187, P = 0.046) in BD. LIMITATIONS:Cross-sectional design and limited control variables. CONCLUSIONS:Elevated FBG and TG levels may be associated with cognitive dysfunction in BD patients. Improving glycolipid metabolism in patients with BD may help to improve certain domain-specific cognitive functions. 10.1016/j.jad.2021.10.100
    Clinical differences between patients with pediatric bipolar disorder with and without a parental history of bipolar disorder. Ramos Bruno Raffa,Librenza-Garcia Diego,Zortea Franco,Watts Devon,Zeni Cristian Patrick,Tramontina Silza,Passos Ives Cavalcante Psychiatry research Pediatric Bipolar Disorder (PBD) is a highly heritable condition responsible for 18% of all pediatric mental health hospitalizations. Despite the heritability of this disorder, few studies have assessed potential differences in the clinical manifestation of PBD among patients with a clear parental history of BD. Additionally, while recent studies suggest that attentional deficits are a potential endophenotypic marker of PBD, it is unclear whether heritability is a relevant contributor to these symptoms. In order to address this gap, the present study assessed 61 youth with PBD (6-17 years old), corresponding to 27 offspring of BD patients, and 31 PBD patients without a parental history of the disorder. All standardized assessments, including the K-SADS-PL-W were performed by trained child and adolescent psychiatrists. We performed a logistic multivariate model using the variables of ADHD, rapid cycling, and lifetime psychosis. Rates of ADHD comorbidity were significantly higher among PBD patients who had a parent with BD. Furthermore, PBD patients who had a parent with BD showed a trend toward significance of earlier symptom onset. PBD offspring did not show increased rates of suicide attempts, rapid cycling, or psychosis. Given these findings, it appears that PBD patients who have a parent with BD may represent a distinct endophenotype of the disorder. Future longitudinal and larger studies are required to confirm our findings. 10.1016/j.psychres.2019.112501
    Rate of OCD and sub-threshold OCD in bipolar disorder patients with first depressive episode. Braverman Leonid,Fuchs Camil,Weizman Abraham,Poyurovsky Michael Psychiatry research Evidence indicates that obsessive-compulsive disorder (OCD) co-occurs with bipolar disorder (BD) at a higher rate than in the general population. Although there is a preliminary indication of a predominant aggregation of OCD in BD patients with bipolar depression (BP-D), no explicit evaluation has previously been undertaken. Using the Structured Clinical Interview for DSM-5 Axis-I disorders and appropriate rating scales, seventy-three BD patients experiencing their first depressive episode were screened for OCD and subthreshold OCD. Nineteen (26%) of the 73 participants in addition to BP-D also met DSM-5 criteria for OCD and 17 (23.2%) patients met criteria for sub-threshold OCD. No differences in demographic and clinical variables evaluated in the study were found between the BP-D patients with and without OCD. Limitations of the study included a relatively small sample size, cross-sectional design and inclusion of only hospitalized BP-D patients. Additional studies are warranted to better define the longitudinal course of comorbid BP-D/OCD, treatment approaches and outcomes of this challenging patient population. Explicit prospective comparison of the rate of DSM-5 OCD and subthreshold OCD in depressive versus manic episodes of bipolar disorder within the same patient is justified. 10.1016/j.psychres.2021.114010
    Pattern of occurrence of obsessive-compulsive symptoms in bipolar disorder. Tonna Matteo,Trinchieri Margherita,Lucarini Valeria,Ferrari Martina,Ballerini Massimo,Ossola Paolo,De Panfilis Chiara,Marchesi Carlo Psychiatry research Apparent comorbidity between Bipolar Disorder (BD) and Obsessive-Compulsive Disorder (OCD) is a common condition, but its meaning has not been clarified yet. The present study aimed to evaluate the pattern of occurrence of obsessive-compulsive symptoms (OCS) in the different phases of BD. One hundred and sixty-five BD patients, 62 (37.5%) euthymic, 34 (20.6%) in hypomanic/manic phase, 43 (26%) in depressive phase and 26 (15.7%) in mixed state, were assessed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Ruminative Response Scale (RRS). In the whole sample, the severity of OCS was associated to the severity of depressive symptoms. The highest severity of OCS (YBOCS total score) was observed in the mixed group and the lowest scores in the hypomanic/manic group. Our findings suggest that OCS in BD patients appear as a state-dependent phenomenon cycling with the mood phases, particularly exacerbating in the context of depressive and mixed states. 10.1016/j.psychres.2021.113715
    A plasma metabolomics study suggests alteration of multiple metabolic pathways in patients with bipolar disorder. Wei Jinxue,Zhao Liansheng,Du Yue,Tian Yang,Ni Peiyan,Ni Rongjun,Wang Yingcheng,Ma Xiaohong,Hu Xun,Li Tao Psychiatry research Previous omics studies have greatly contributed to our knowledge of bipolar disorder. Metabolomics is a relatively new field of omics science that can provide complementary insight into data obtained from genomics, transcriptomics or proteomics analyses. In this study, we aimed to identify metabolic pathways associated with bipolar disorder. We performed a liquid chromatography-mass spectrometry-based study to identify plasma metabolic profiles in patients with bipolar disorder (N = 91) and healthy controls (N = 92). Multivariate features selection by sparse partial least square-discriminant analysis combined with metabolite set enrichment analysis were used to identify metabolites and biological pathways that discriminate patients with bipolar disorder from healthy controls. The results showed that eighty metabolites in the plasma were identified to discriminate patients with bipolar disorder from healthy controls, and nine metabolic pathways, i.e., (1) glycine and serine metabolism, (2) glutamate metabolism, (3) arginine and proline metabolism, (4) tyrosine metabolism, (5) catecholamine biosynthesis, (6) purine metabolism, (7) amino sugar metabolism, (8) ammonia recycling, and (9) carnitine synthesis, were identified to be altered in bipolar disorder compared to healthy controls. We conclude that the 80 metabolites and nine metabolic pathways identified might serve as biomarkers to distinguish bipolar disorder patients from healthy controls. 10.1016/j.psychres.2021.113880
    Testing the association of serum uric acid levels with behavioral and clinical characteristics in subjects with major affective disorders: A cross-sectional study. Bartoli Francesco,Crocamo Cristina,Bava Mattia,Castagna Gloria,Di Brita Carmen,Riboldi Ilaria,Trotta Giulia,Verrengia Enrica,Clerici Massimo,Carrà Giuseppe Psychiatry research Previous research has hypothesized a role for serum uric acid as a marker of mental disorders and related behaviors, possibly due to its link with purinergic transmission and antioxidant activity. We tested the association of serum uric acid levels with specific behavioral and clinical characteristics in 99 individuals suffering from major affective disorders. Subjects were assessed and interviewed using the Kessler Psychological Distress Scale, the Columbia-Suicide Severity Rating Scale, the Modified Overt Aggression Scale, and the Barratt Impulsiveness Scale. We found that psychological distress and suicidal ideation severity were associated with lower uric acid serum levels. On the other hand, verbal aggression and history of violence were associated with higher levels of serum uric acid. However, according to linear regression analyses, there were no behavioral and clinical characteristics independently associated with serum uric acid. Serum uric acid levels were influenced by creatinine and BMI, as well as, possibly, by white blood cells count and gender. Despite some limitations, these results suggest that no behavioral / clinical features are associated with variations of serum uric acid, which rather seem attributable to specific biochemical and metabolic parameters. Nevertheless, the role of purinergic system in different mental disorders and behavioral abnormalities, deserves further research. 10.1016/j.psychres.2018.08.039
    The biology of aggressive behavior in bipolar disorder: A systematic review. Fico Giovanna,Anmella Gerard,Pacchiarotti Isabella,Verdolini Norma,Sagué-Vilavella Maria,Corponi Filippo,Manchia Mirko,Vieta Eduard,Murru Andrea Neuroscience and biobehavioral reviews Aggressive behavior (AB) represents a public health concern often associated with severe psychiatric disorders. Although most psychiatric patients are not aggressive, untreated psychiatric illness, including bipolar disorder (BD), may associate with an increased risk of AB. Accurate predictive models of AB are still lacking and it is crucial to delineate AB biomarkers state of the art in BD. We performed a systematic review according to PRISMA guidelines to identify biological correlates of AB in BD. Final results included 20 studies: 10 involving genetic and 10 other biological AB biomarkers (total sample size N = 5,181). Our results pointed to a serotoninergic hypoactivation in violent suicidal BD patients. Similarly, BD violent suicide attempters had a blunted hypothalamic-pituitary-adrenal (HPA) activity. Violent behavior in BD was associated with a chronic inflammatory state. While the role of lipids as biomarkers for AB remains equivocal, uric acid appears as a potential biomarker for hetero-AB in BD. Available data can be useful in the fulfill of specific biomarkers of AB in BD, ultimately leading to the development of accurate predictive models. 10.1016/j.neubiorev.2020.09.015
    Gut Microbiota, Glucose, Lipid, and Water-Electrolyte Metabolism in Children With Nonalcoholic Fatty Liver Disease. Pan Xiongfeng,Kaminga Atipatsa C,Liu Aizhong,Wen Shi Wu,Luo Miyang,Luo Jiayou Frontiers in cellular and infection microbiology There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children's Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., , , and ) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., ) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., , , , and ) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children. 10.3389/fcimb.2021.683743
    Psychopharmacological treatment of psychotic mania and psychotic bipolar depression compared to non-psychotic mania and non-psychotic bipolar depression. Bjørklund Louise B,Horsdal Henriette T,Mors Ole,Gasse Christiane,Østergaard Søren D Bipolar disorders OBJECTIVES:An evidence base for the treatment of mania and bipolar depression with psychotic symptoms is lacking. Nevertheless, clinicians may have a preference for treating episodes of bipolar disorder with or without psychotic symptoms in different ways, which is likely to reflect notions of differential efficacy of treatments between these subtypes. This study aimed to investigate whether the psychopharmacological treatment of psychotic and non-psychotic episodes of mania and bipolar depression, respectively, differs in clinical practice. METHODS:We conducted a register-based study assessing the psychopharmacological treatment of all individuals receiving their first diagnosis of mania or bipolar depression between 2010 and 2012. The psychopharmacological treatment within 3 months following the time of diagnosis was considered. Potential differences in psychopharmacological treatment between the psychotic and non-psychotic subtypes of mania and bipolar depression, respectively, were investigated by means of Pearson's χ test and logistic regression adjusted for sex and age at diagnosis of bipolar disorder. RESULTS:A total of 827 patients were included in the analyses. The adjusted odds ratio (aOR) for treatment with an antipsychotic was 1.71 (95% confidence interval [CI]: 1.18-2.48, P<.01) for psychotic mania and 3.89 (95% CI: 1.95-7.76, P<.001) for psychotic bipolar depression. The aOR for treatment with the combination of an antipsychotic and an anticonvulsant was 1.60 (95% CI: 1.06-2.43, P<.05) for psychotic mania. The aOR for treatment with the combination of an antipsychotic and an antidepressant was 2.50 (95% CI: 1.43-4.37, P<.01) for bipolar psychotic depression. CONCLUSIONS:It would be of interest to conduct studies evaluating whether antipsychotics represent the superior pharmacological treatment for psychotic mania and psychotic bipolar depression. 10.1111/bdi.12504
    Altered functional connectivity of right inferior frontal gyrus subregions in bipolar disorder: a resting state fMRI study. Zhang Li,Li Wenfei,Wang Long,Bai Tongjian,Ji Gong-Jun,Wang Kai,Tian Yanghua Journal of affective disorders The right inferior frontal gyrus (rIFG) is a key cortical node in the circuits of emotion and cognitive control, and it has been frequently associated with bipolar disorder (BP); however, a reliable pattern of aberrant rIFG activation and connectivity in bipolar disorder has yet to be established. To further elucidate rIFG abnormalities in different states of bipolar disorder, we examined activation and functional connectivity (FC) in five subregions of rIFG in bipolar disorder. A total of 83 participants, including those with bipolar depression (BPD; n = 25) and bipolar mania (BPM; n = 37) along with healthy control (HC) subjects (n = 26), were examined by resting state functional magnetic resonance imaging (rs-fMRI). Both BPD and BPM groups showed higher values of amplitude of low-frequency fluctuations (ALFF) than healthy control in four of the five rIFG subregions except cluster 2(posterior-ventral rIFG). Using five subregions of rIFG as seeds, the decreased FC in bipolar disorder was mainly between posterior-ventral rIFG(cluster 2) and multiple brain regions including the postcentral gyrus, the precentral gyrus, paracentral lobule, lingual Gyrus, fusiform and cerebellum posterior lobe. These results indicated that local activity and FC were altered within specific subregions of the rIFG in BP. These findings may provide the distinct functional connectivity of rIFG subregions in BP and suggest that the cluster2 (posterior-ventral rIFG) circuitry plays a crucial role in BP. Also, such abnormalities might help define a more precise intervention targets. 10.1016/j.jad.2020.03.122
    Aberrant brain network topology in the frontoparietal-limbic circuit in bipolar disorder: a graph-theory study. Zhang Li,Wu Huiling,Zhang Aiguo,Bai Tongjian,Ji Gong-Jun,Tian Yanghua,Wang Kai European archives of psychiatry and clinical neuroscience Characterizing the properties of brain networks across mood states seen in bipolar disorder (BP) can provide a deeper insight into the mechanisms involved in this type of affective disorder. In this study, graph theoretical methods were used to examine global, modular and nodal brain network topology in the resting state using functional magnetic resonance imaging data acquired from 95 participants, including those with bipolar depression (BPD; n = 30) and bipolar mania (BPM; n = 39) and healthy control (HC) subjects (n = 26). The threshold value of the individual subjects' connectivity matrix varied from 0.15 to 0.30 with steps of 0.01. We found that: (1) at the global level, BP patients showed a significantly increased global efficiency and synchronization and a decreased path length; (2) at the nodal level, BP patients showed impaired nodal parameters, predominantly within the frontoparietal and limbic sub-network; (3) at the module level, BP patients were characterized by denser FCs (edges) between Module III (the front-parietal system) and Module V (limbic/paralimbic systems); (4) at the nodal level, the BPD and BPM groups showed state-specific differences in the orbital part of the left superior-frontal gyrus, right putamen, right parahippocampal gyrus and left fusiform gyrus. These results revealed abnormalities in topological organization in the whole brain, especially in the frontoparietal-limbic circuit in both BPD and BPM. These deficits may reflect the pathophysiological processes occurring in BP. In addition, state-specific regional nodal alterations in BP could potentially provide biomarkers of conversion across different mood states. 10.1007/s00406-020-01219-7
    Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment. Lucidi Lorenza,Pettorruso Mauro,Vellante Federica,Di Carlo Francesco,Ceci Franca,Santovito Maria Chiara,Di Muzio Ilenia,Fornaro Michele,Ventriglio Antonio,Tomasetti Carmine,Valchera Alessandro,Gentile Alessandro,Kim Yong-Ku,Martinotti Giovanni,Fraticelli Silvia,Di Giannantonio Massimo,De Berardis Domenico International journal of molecular sciences The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD. 10.3390/ijms22073723
    Prevalence of childhood trauma among adults with affective disorder using the Childhood Trauma Questionnaire: A meta-analysis. Zhang Simei,Lin Xiujin,Yang Tingyu,Zhang Shengjie,Pan Yuli,Lu Jianping,Liu Jianbo Journal of affective disorders BACKGROUND:Childhood trauma is associated with major depressive disorder (MDD) and bipolar disorder (BD) in adults. However, no meta-analysis was performed on the prevalence of different types of childhood trauma in adults with affective disorders, using the Childhood Trauma Questionnaire (CTQ). METHODS:Four databases were used to search articles regarding the prevalence of childhood emotional abuse (CEA), childhood physical abuse (CPA), childhood sexual abuse (CSA), childhood physical neglect (CPN), and childhood emotional neglect (CEN) in patients with MDD and BD using the CTQ. RESULTS:A total of 17 and 11 articles were found analyzing patients with MDD and BD, respectively. A pooled prevalence rate of 33.0% and 30.0% for CEA, 17.0% and 18.0% for CPA, 19.0% and 22.0% for CSA, 37.0% and 31.0% for CEN, and 31% and 30.0% for CPN was found in patients with MDD and BD respectively. A difference in 95% confidence interval in the CSA rate between men and women was found in patients with MDD in the gender subgroup and in the rate of some types of childhood trauma in the continent subgroup in both patient types. LIMITATIONS:A limited number of articles were included in some continents, thus, the heterogeneity in the meta-analysis was generally high. CONCLUSION:The prevalence of CEA, CEN, and CPN in patients with affective disorders was relatively high, whereas that of CPA and CSA was relatively low. These childhood traumas might be affected by continent and gender. 10.1016/j.jad.2020.07.001
    Childhood trauma associates with clinical features of bipolar disorder in a sample of Chinese patients. Li Xian-Bin,Liu Jin-Tong,Zhu Xiong-Zhao,Zhang Liang,Tang Yi-Lang,Wang Chuan-Yue Journal of affective disorders OBJECTIVES:Childhood trauma is a major public health problem which has a long-term consequence, a few studies have examined the relationship between childhood trauma and clinical features of bipolar disorder, most in western culture, with no such studies done in Chinese culture. METHODS:The CTQ-SF was administered to 132 Chinese patients with DSM-IV bipolar disorder. Participants also completed the Childhood Experience of Care and Abuse Questionnaire (CECA.Q), the Impact of Events Scale-Revised (IES-R), and the State-Trait Anxiety Inventory (STAI). The CTQ-SF cut-off scores for exposure were used to calculate the prevalence of trauma. The relationship between childhood trauma and clinical features of bipolar disorder were examined. RESULTS:The internal consistency of CTQ-SF was good (Cronbach׳s α=0.826) and four week test-retest reliability was high (r=0.755). 61.4% of this sample reported physical neglect (PN) in childhood, followed by emotional neglect (EN, 49.6%), sexual abuse (SA, 40.5%), emotional abuse (EA, 26.0%) and physical abuse (PA,13.1%). Significant negative correlations existed between age of onset and EA and EN score (r=-0.178~-0.183, p<0.05). Significant positive correlations were observed between EA, CTQ-SF total score and intrusion and hyper-arousal scores of IES-R (r=0.223~0.309, p<0.05). Similarly, significant positive correlations were found between EN, PN, CTQ-SF total and STAI score (r=0.222~0.425, p<0.05). LIMITATIONS:Data on childhood trauma were derived from a retrospective self-report questionnaire without independent corroboration. A number of potential patients (more severe or chronic patients) was excluded because they were either refused to participate or inappropriate to participate in research. CONCLUSIONS:Significant number of subjects in patients with BD reported experience of childhood abuse and neglect. Exposure to childhood trauma is associated with age of onset of illness, co morbid PTSD and anxiety symptoms. To study the pathogenesis of childhood trauma on bipolar disorder and explanation the interaction between childhood trauma and susceptibility genes are proposed. 10.1016/j.jad.2014.06.017
    Immature defense mechanisms mediate the relationship between childhood trauma and onset of bipolar disorder. Wang Leilei,Yin Yi,Bian Qingtao,Zhou Yanfang,Huang Junchao,Zhang Ping,Chen Song,Fan Hongzhen,Cui Yimin,Luo Xingguang,Tan Shuping,Wang Zhiren,Li Chiang-Shan R,Tian Baopeng,Tian Li,Hong L Elliot,Tan Yunlong Journal of affective disorders BACKGROUND:Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms. METHODS:Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively. RESULTS:BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ. CONCLUSIONS:Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders. 10.1016/j.jad.2020.10.029
    Correlates of violent suicide attempts in patients with bipolar disorder. Rosso Gianluca,Albert Umberto,Bramante Stefano,Aragno Elena,Quarato Federica,Di Salvo Gabriele,Maina Giuseppe Comprehensive psychiatry BACKGROUND:Suicide is one of the leading causes of death in bipolar disorder (BD); violent suicide attempts are associated with the highest level of lethality. We aimed to evaluate factors related to the risk of violent suicide in a large naturalistic sample of patients with BD; in addition, we analyzed the rates of lifetime suicide attempts and the variables associated with suicidal behavior. METHODS:We recruited 847 patients with BD. Patients were grouped according to whether they had a lifetime history of suicide attempts and, among suicide attempters, subjects who had used a violent suicide method were compared with those who had attempted suicide with a nonviolent method. Comparisons were performed using χ2 tests for categorical variables and ANOVA for continuous variables. Logistic regression (LogReg) was used to identify explanatory variables associated with violent suicide attempts (dependent variable). RESULTS:Two hundred and two patients (24%) had a lifetime history of suicide attempts. Subjects with at least one lifetime suicide attempt showed longer duration of illness (22.4±14.1 years vs 19.9±14.2 years: p 0.028), more lifetime hypomanic episodes (3.3±4.3 vs 2.3±3.1: p0.001), more lifetime depressive episodes (6.0±4.4 vs 4.7±4.1: p<0.001), higher rates of lifetime psychiatric comorbidities (50.0% vs 41.3%: p 0.029), higher rates of lifetime medical comorbidities (58.0% vs 48.9%: p 0.028) and higher rates of reduced HDL cholesterol (46.2% vs 36.7%: p 0.030). Among suicide attempters, fifty-two patients (30.6%) attempted suicide with a violent method. We found more men in the group of violent suicide attempters than in the group of nonviolent suicide attempters (65% vs 28%; p: <0.001). Moreover subjects with previous violent attempts showed higher mean values of weight (80.5±18.3 vs 69.4±14.7: p<0.001), body mass index (27.8±5.6 vs 25.2±4.7: p<0.003) and waist circumference (98.7±18.5 vs 92.4±14.3: p 0.032). The LogReg analysis confirmed the association of violent attempts with male gender (p: <0.001; Phi: 0.35) and higher waist circumference (p: <0.001; Cohen's d: 0.39). LIMITATIONS:In our research we analyzed lifetime suicide attempts, but the sample does not include completed suicides, meaning that we are unable to test whether the results are generalizable to suicide deaths. Moreover, some relevant variables, such as medical comorbidities/metabolic parameters at the time of suicide attempts and previous medication, were not collected. Another limitation concerns the heterogeneity of recruited patients in terms of clinical characteristics (e.g.: medical conditions, drug treatments), with potential confounding factors. CONCLUSIONS:The present study confirms the association between male gender and violent suicide and suggests a correlation between obesity and the use of violent suicide methods. The relationship between obesity and suicidal behaviour is worthy of interest and deserves to be explored by further studies. 10.1016/j.comppsych.2019.152136
    Impact of Childhood Trauma and Attachment on Resilience in Remitted Patients with Bipolar Disorder. Citak Cihad,Erten Evrim Journal of affective disorders BACKGROUND:Childhood trauma has been reported to be associated with severe course of illness, insecure attachment, and lower resilience in bipolar disorder. We aimed to examine the impact of childhood trauma on resilience and possible mediating role of attachment on this impact in bipolar disorder. METHODS:The study group comprised of 110 remitted patients with bipolar disorder. Hamilton Depression Rating Scale (HAM-D) and Young Mani Rating Scale (YMRS) are administered to verify remission. Childhood trauma questionnaire (CTQ-SF), Experiences in Close Relationships-revised (ECR-R), and Resilience Scale for Adults (RSA) scales administered to all patients. RESULTS:More than half of patients in bipolar disorder group reported childhood trauma. HAM-D scores were positively associated with childhood trauma total scores and emotional abuse scores, negatively associated with resilience, with attachment-related anxiety. Total childhood trauma scores were associated with lower scores of resilience, higher scores of attachment-related anxiety and avoidance. Resilience scores were negatively associated with attachment-related anxiety and avoidance. Impact of childhood trauma on resilience was partly mediated by attachment-related anxiety and avoidance, respectively. LIMITATIONS:The cross-sectional design of this study is a limitation in terms of determining causality of the identified relationships. CONCLUSIONS:Childhood traumas are associated with lower resilience and higher attachment-related anxiety and avoidance. Attachment-related anxiety and avoidance partly mediated the negative effect of childhood trauma on resilience. Since resilience is associated with increased quality of life in bipolar disorder, it might be helpful to develop attachment-informed psychosocial interventions to ameliorate the detrimental effect of childhood trauma on resilience. 10.1016/j.jad.2020.11.025
    Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches. Soto-Angona Óscar,Anmella Gerard,Valdés-Florido María José,De Uribe-Viloria Nieves,Carvalho Andre F,Penninx Brenda W J H,Berk Michael BMC medicine BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in over 5% of the parenchyma in the absence of excessive alcohol consumption. It is more prevalent in patients with diverse mental disorders, being part of the comorbidity driving loss of life expectancy and quality of life, yet remains a neglected entity. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and increases the risk for cirrhosis and hepatic carcinoma. Both NAFLD and mental disorders share pathophysiological pathways, and also present a complex, bidirectional relationship with the metabolic syndrome (MetS) and related cardiometabolic diseases. MAIN TEXT:This review compares the demographic data on NAFLD and NASH among the global population and the psychiatric population, finding differences that suggest a higher incidence of this disease among the latter. It also analyzes the link between NAFLD and psychiatric disorders, looking into common pathophysiological pathways, such as metabolic, genetic, and lifestyle factors. Finally, possible treatments, tailored approaches, and future research directions are suggested. CONCLUSION:NAFLD is part of a complex system of mental and non-communicable somatic disorders with a common pathogenesis, based on shared lifestyle and environmental risks, mediated by dysregulation of inflammation, oxidative stress pathways, and mitochondrial function. The recognition of the prevalent comorbidity between NAFLD and mental disorders is required to inform clinical practice and develop novel interventions to prevent and treat these complex and interacting disorders. 10.1186/s12916-020-01713-8
    Non-alcoholic fatty liver disease in a sample of individuals with bipolar disorders: results from the FACE-BD cohort. Godin Ophelia,Leboyer Marion,Belzeaux Raoul,Bellivier Frank,Loftus Joséphine,Courtet Philippe,Dubertret Caroline,Gard Sebastien,Henry Chantal,Llorca Pierre-Michel,Schwan Raymund,Passerieux Christine,Polosan Mircea,Samalin Ludovic,Olié Emilie,Etain Bruno, Acta psychiatrica Scandinavica OBJECTIVE:Non-Alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in Western populations. While obesity and metabolic abnormalities are highly frequent in bipolar disorders (BD), no studies have been performed to estimate the prevalence of NALFD in individuals with BD. The aim of our study is to estimate the prevalence of NAFLD and to identify the potential associated risk factors in a large sample of BD individuals. METHODS:Between 2009 and 2019, 1969 BD individuals from the FACE-BD cohort were included. Individuals with liver diseases, Hepatitis B or C, and current alcohol use disorders were excluded from the analyses. A blood sample was drawn from participants. Screening of NAFLD was determined using fatty liver index (FLI). Individuals with FLI> 60 were considered as having NAFLD. RESULTS:The prevalence of NAFDL in this sample was estimated at 28.4%. NAFLD was observed in 40% of men and 21% of women. NAFLD was independently associated with older age, male gender, sleep disturbances, and current use of atypical antipsychotics or anxiolytics. As expected, the prevalence of NALFD was also higher in individuals with overweight and in those with metabolic syndrome. CONCLUSIONS:This study reinforces the view that individuals with BD are highly vulnerable to metabolic and cardiovascular diseases. The prevalence of NAFLD in individuals with BD was two times higher than the prevalence reported in the general population. The regular screening of the MetS in individuals with BD should be therefore complemented by the additional screening of NAFLD among these vulnerable individuals. 10.1111/acps.13239
    Predictive modeling for response to lithium and quetiapine in bipolar disorder. Kim Thomas T,Dufour Steven,Xu Colin,Cohen Zachary D,Sylvia Louisa,Deckersbach Thilo,DeRubeis Robert J,Nierenberg Andrew A Bipolar disorders OBJECTIVES:Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine-learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples. METHODS:Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set. RESULTS:Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention-deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self-injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models. CONCLUSION:ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder. 10.1111/bdi.12752
    Resilience and Cognitive Function in Patients With Schizophrenia and Bipolar Disorder, and Healthy Controls. Deng Mengjie,Pan Yunzhi,Zhou Li,Chen Xudong,Liu Chang,Huang Xiaojun,Tao Haojuan,Pu Weidan,Wu Guowei,Hu Xinran,He Zhong,Xue Zhimin,Liu Zhening,Rosenheck Robert Frontiers in psychiatry This study compared adaptive resilience among patients with schizophrenia, bipolar disorder, and healthy controls, and examined the relationship of resilience to cognitive function. A sample of 81 patients diagnosed with schizophrenia, 34 with bipolar disorder, and 52 healthy controls completed the Connor-Davidson Resilience Scale (CD-RISC) and cognitive tests of verbal comprehension, executive functioning, and working memory. Paired comparison of diagnostic groups on CD-RISC and cognitive tests was conducted. Linear regression was used to identify the independent association of clinical diagnoses and neurocognition with resilience deficits. Both patient groups showed significantly lower CD-RISC scores and poorer cognitive function than healthy controls and the schizophrenia group scored lower than bipolar group on these measures as well. CD-RISC scores were positively correlated with all three cognitive measures in the entire sample but not within the diagnostic subgroups. Multiple regression analysis showed differences in CD-RISC between diagnostic groups were not mediated by differences in these three measures of neurocognition. Schizophrenia and bipolar disorder are associated with impairments in both resilience and cognitive function but the impairment in resilience appears to be independent of deficits in cognitive function measured here and may reflect unmeasured dimensions of cognitive function, other impairments or environmental factors. 10.3389/fpsyt.2018.00279
    Light exposure at night and sleep quality in bipolar disorder: The APPLE cohort study. Esaki Yuichi,Kitajima Tsuyoshi,Obayashi Kenji,Saeki Keigo,Fujita Kiyoshi,Iwata Nakao Journal of affective disorders BACKGROUND:Sleep disturbance in bipolar disorder (BD) is common and is associated with a risk for mood episode recurrence. Thus, it is important to identify factors that are related to sleep disturbance in BD. This cross-sectional study investigated the association between exposure to light at night (LAN) and sleep parameters in patients with BD. METHODS:The sleep parameters of 175 outpatients with BD were recorded using actigraphy at their homes for seven consecutive nights and were evaluated using the Insomnia Severity Index (ISI). The average LAN intensity in the bedroom during bedtime and rising time was measured using a portable photometer, and the participants were divided into two groups: "Light" (≥5 lx) and "Dark" (<5 lx). The association between LAN and sleep parameters was tested with multivariable analysis by adjusting for potential confounder such as age, gender, current smoker, mood state, day length, daytime light exposure, and sedative medications. RESULTS:After adjusting for potential confounder, the actigraphy sleep parameters showed significantly lower sleep efficiency (mean, 80.1%vs. 83.4%; p = 0.01), longer log-transformed sleep onset latency (2.9 vs. 2.6 min; p = 0.01), and greater wake after sleep onset (51.4 vs. 41.6 min; p = 0.02) in the Light group than in the Dark group. Whereas, there were no significant differences in the ISI scores between the groups. LIMITATIONS:This was a cross-sectional study; therefore, the results do not necessarily imply that LAN causes sleep disturbance. CONCLUSIONS:Reducing LAN exposure may contribute to improved sleep quality in patients with BD. 10.1016/j.jad.2019.07.031
    Psychopathology in 7-year-old children with familial high risk of developing schizophrenia spectrum psychosis or bipolar disorder - The Danish High Risk and Resilience Study - VIA 7, a population-based cohort study. Ellersgaard Ditte,Jessica Plessen Kerstin,Richardt Jepsen Jens,Soeborg Spang Katrine,Hemager Nicoline,Klee Burton Birgitte,Jerlang Christiani Camilla,Gregersen Maja,Søndergaard Anne,Uddin Md Jamal,Poulsen Gry,Greve Aja,Gantriis Ditte,Mors Ole,Nordentoft Merete,Elgaard Thorup Anne Amalie World psychiatry : official journal of the World Psychiatric Association (WPA) This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ) or bipolar disorder (FHR-BP) with population-based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven-year-old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM-IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD-Rating Scale, the Test Observation Form, and the State-Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR-SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2-5.7, p < 0.001) and FHR-BP children (35.6%, OR=3.1, 95% CI: 1.8-5.3, p < 0.001) compared with controls (15.2%). FHR-SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR-BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR-SZ children. Level of functioning was lower in both FHR-SZ children (CGAS mean score = 68.2; 95% CI: 66.3-70.2, p < 0.0001) and FHR-BP children (73.7; 95% CI: 71.2-76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9-79.9). In conclusion, already at the age of seven, FHR-SZ and FHR-BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children. 10.1002/wps.20527
    Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder. Frangou Sophia,Dima Danai,Jogia Jigar NeuroImage Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients' relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis. 10.1016/j.neuroimage.2016.08.066
    Impact of childhood trauma and affective temperament on resilience in bipolar disorder. Kesebir Sermin,Ünübol Başak,Tatlıdil Yaylacı Elif,Gündoğar Duru,Ünübol Hüseyin International journal of bipolar disorders BACKGROUND:The aim of this study was to investigate whether childhood trauma (CT) and affective temperament have an impact on resilience in bipolar patients. METHODS:One hundred cases with bipolar disorder (BD) diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) were evaluated consecutively in their euthymic period during outpatient follow-up interviews. Diagnostic interviews were done with SCID-I, affective temperament was evaluated with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire, and resilience was evaluated with the Resilience Scale for Adults (RSA). The presence of CT was determined and measured with the Childhood Trauma Questionnaire (CTQ). RESULTS:Among the bipolar patients, it was found that 35 cases (35%) were CT+. Depressive, cyclothymic, and anxious temperament scores were higher in CT+ cases. However, resilience scores were higher in CT- cases. In bipolar patients with and without childhood trauma, the relationship between temperament and resilience appears to be different. A negative relation between sexual abuse, emotional abuse, emotional neglect, and anxious temperament scores and resilience scores was shown in regression analysis. CONCLUSIONS:CT and affective temperament both have an impact on resilience in bipolar patients. 10.1186/s40345-015-0023-3
    Resilience concepts in psychiatry demonstrated with bipolar disorder. Angeler David G,Allen Craig R,Persson Maj-Liz International journal of bipolar disorders BACKGROUND:The term resilience describes stress-response patterns of subjects across scientific disciplines. In ecology, advances have been made to clearly distinguish resilience definitions based on underlying mechanistic assumptions. Engineering resilience (rebound) is used for describing the ability of subjects to recover from adverse conditions (disturbances), and is the rate of recovery. In contrast, the ecological resilience definition considers a systemic change: when complex systems (including humans) respond to disturbances by reorganizing into a new regime (stable state) where structural and functional aspects have fundamentally changed relative to the prior regime. In this context, resilience is an emergent property of complex systems. We argue that both resilience definitions and uses are appropriate in psychology and psychiatry, but although the differences are subtle, the implications and uses are profoundly different. METHODS:We borrow from the field of ecology to discuss resilience concepts in the mental health sciences. RESULTS:In psychology and psychiatry, the prevailing view of resilience is adaptation to, coping with, and recovery (engineering resilience) from adverse social and environmental conditions. Ecological resilience may be useful for describing vulnerability, onset, and the irreversibility patterns of mental disorders. We discuss this in the context of bipolar disorder. CONCLUSION:Rebound, adaptation, and coping are processes that are subsumed within the broader systemic organization of humans, from which ecological resilience emanates. Discerning resilience concepts in psychology and psychiatry has potential for a mechanistically appropriate contextualization of mental disorders at large. This might contribute to a refinement of theory and contextualize clinical practice within the broader systemic functioning of mental illnesses. 10.1186/s40345-017-0112-6
    Resilience and impulsivity in euthymic patients with bipolar disorder. Choi Jae-Won,Cha Boseok,Jang Jihoon,Park Chul-Soo,Kim Bong-Jo,Lee Cheol-Soon,Lee So-Jin Journal of affective disorders BACKGROUND:Stress plays an important role in the onset and recurrence of bipolar disorder (BD). Resilience is the ability to cope with stress or adversity. Few studies have examined resilience in BD, and this study aimed to investigate the clinical correlates of resilience in euthymic patients with BD. METHODS:A total of 62 outpatients with BD type I, II, and not otherwise specified (NOS) who were in remission and 62 healthy individuals matched with the BD group in terms of age and sex were recruited. All participants completed the Connor-Davidson Resilience Scale and Barratt Impulsiveness Scale. A psychiatrist interviewed the subjects to assess clinical characteristics. Multiple linear regression analysis was used to determine factors associated with resilience. RESULTS:The BD group had significantly higher levels of impulsivity and lower levels of resilience compared with the control group. Degree of impulsivity, number of depressive episodes, Clinical Global Impression (CGI) scores, and length of education were significantly correlated with resilience. Attention impulsivity, non-planning impulsivity, and number of depressive episodes were associated with low levels of resilience, even when age, sex, length of education, and CGI scores were controlled. LIMITATIONS:Because tertiary hospital patients were recruited, the generalizability of the findings is limited. CONCLUSIONS:This study shows that low levels of resilience are related to high levels of impulsivity and to an increased number of depressive episodes in euthymic patients with BD. Given the reciprocal relationship between resilience and impulsivity, efforts to enhance resilience and reduce impulsivity may make important contributions to the treatment of patients with BD. 10.1016/j.jad.2014.08.056
    Resilience and insight in euthymic patients with bipolar disorder. Şenormancı Güliz,Güçlü Oya,Özben İlker,Karakaya Fatma Nur,Şenormancı Ömer Journal of affective disorders BACKGROUND:The relationship between resilience and insight may be of potential importance for coping with stress in bipolar disorder (BD). The aim of this study was to investigate if there was a relation between insight and resilience in euthymic patients with BD and also to analyze the associations between resilience, impulsivity, aggression, alcohol use and affective temperament. METHODS:142 patients with BD type I in remission period were involved. Resilience Scale for Adults-Turkish version, Schedule for Assessment of Insight, Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire, Barratt Impulsiveness Scale, Buss-Perry Aggression Questionnaire, Michigan Alcoholism Screening Test were used. RESULTS:Total insight scores were negatively correlated with the scores of perception of future. As distinct from other subscales of resilience, family cohesion had independent significant associations with insight in relabelling of psychotic experiences and attention impulsivity. There was no relationship between total insight and total resilience scores. Resilience scores were negatively correlated with number of depressive episodes and number of suicide attempts. Degree of aggression, degree of impulsivity, scores of depressive and hyperthymic temperament significantly predicted resilience. LIMITATIONS:Recruitment of patients from a tertiary centre limits the generalizability of the findings. CONCLUSIONS:Better insight was related to negative perception of the future and did not have significant associations with total resilience. Number of depressive episodes, number of past suicide attempts correlated with resilience, emphasizing the importance of interventions to increase resilience in BD. 10.1016/j.jad.2020.01.079
    Effects of resilience on quality of life in patients with bipolar disorder. Lee Dongyun,Cha Boseok,Park Chul-Soo,Kim Bong-Jo,Lee Cheol-Soon,Lee So-Jin,Seo Ji-Yeong,Cho Young Ah,Ha Jong Hun,Choi Jae-Won Journal of affective disorders BACKGROUND:Few studies have examined the effects of resilience on quality of life (QOL) in patients with bipolar disorder (BD). Therefore, this study investigated the association between resilience and QOL in patients with BD and compared it to the relationship between resilience and QOL in healthy individuals. METHODS:Participants were 68 euthymic patients with BD and 68 age-, sex-, and length of education-matched controls. Sociodemographic characteristics and clinical variables of the two groups were obtained using face-to-face interviews, and all participants completed the Connor-Davidson Resilience Scale, the World Health Organization QOL-Brief Form. RESULTS:The QOL of the BD group was significantly impaired compared with that of the controls. Degree of resilience, number of depressive episodes, Clinical Global Impression scores, degree of impulsivity, and length of education were significantly correlated with QOL in the BD group. Resilience was significantly associated with overall QOL, physical subdomains of QOL, psychological subdomains of QOL, social subdomains of QOL, and environmental subdomains of QOL in the BD group, even after controlling for confounders. In the control group, resilience was significantly associated with overall QOL, the physical subdomains of QOL, psychological subdomains of QOL, and social subdomains of QOL. LIMITATIONS:The number of participants in each group was 68, which is a relatively small sample size. CONCLUSIONS:Resilience in patients with BD was independently and positively correlated with various areas of QOL. Various strategies to reinforce resilience in patients with BD are needed to improve the low QOL in this population. 10.1016/j.jad.2016.08.075
    Quality of life in stabilized outpatients with bipolar I disorder: Associations with resilience, internalized stigma, and residual symptoms. Post Fabienne,Pardeller Silvia,Frajo-Apor Beatrice,Kemmler Georg,Sondermann Catherine,Hausmann Armand,Fleischhacker W Wolfgang,Mizuno Yuya,Uchida Hiroyuki,Hofer Alex Journal of affective disorders OBJECTIVES:Improving Quality of Life (QoL) is an important objective in the treatment of bipolar disorder. The aim of the current study was to examine to which extent resilience, internalized stigma, and psychopathology are correlated to QoL. METHODS:We recruited 60 outpatients diagnosed with bipolar I disorder according to DSM-IV criteria and 77 healthy control subjects from the general community. In patients, symptoms were quantified by the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS) and internalized stigma by the Internalized Stigma of Mental Illness (ISMI) scale. In order to assess QoL and resilience, the Berliner Lebensqualitätsprofil (BELP) and the Resilience Scale (RS-25) were used in both patients and control subjects. RESULTS:Despite presenting with a very mild symptom level and relatively low internalized stigma, patients with bipolar I disorder indicated significantly lower QoL and resilience as compared to healthy control subjects. In patients, QoL correlated significantly with resilience, internalized stigma, and residual symptoms of depression. No significant correlations were observed between QoL and residual manic symptoms. LIMITATIONS:The cross-sectional design and the relatively small sample size limit the generalizability of our results. Furthermore, levels of resilience and internalized stigma may change over the course of the illness and have different impacts on the long-term outcome of patients with bipolar disorder. CONCLUSION:Our results show that QoL of patients suffering from bipolar I disorder, even when only mildly ill, is strongly associated with the degree of resilience and internalized stigma, and that particularly residual depressive symptoms have a negative impact on QoL. In addition to drug treatment, psychotherapeutic approaches should be applied to strengthen resilience, to reduce internalized stigma, and, ultimately, to improve quality of life. 10.1016/j.jad.2018.05.055
    Resilience dimensions and mental health outcomes in bipolar disorder in a follow-up study. Echezarraga A,Calvete E,González-Pinto A M,Las Hayas C Stress and health : journal of the International Society for the Investigation of Stress The individual process of resilience has been related to positive outcomes in mental disorders. We aimed (a) to identify the resilience domains from the Resilience Questionnaire for Bipolar Disorder that are associated cross sectionally and longitudinally with mental health outcomes in bipolar disorder (BD) and (b) to explore cross-lagged associations among resilience factors. A clinical adult sample of 125 patients diagnosed with BD (62.10% female, mean age = 46.13, SD = 10.89) gave their informed consent and completed a battery of disease-specific tools on resilience, personal recovery, symptomatology, psychosocial functioning, and quality of life, at baseline and at follow-up (n = 63, 58.10% female, mean age = 45.13, SD = 11.06, participation rate = 50.40%). Resilience domains of self-management of BD, turning point, self-care, and self-confidence were significantly associated with mental health indicators at baseline. In addition, self-confidence at baseline directly predicted an increase in personal recovery at follow-up, and self-confidence improvement mediated the relationship between interpersonal support and self-care at baseline and personal recovery at follow-up. These findings highlight that resilience domains are significantly associated with positive mental health outcomes in BD and that some predict personal recovery at follow-up. Moreover, some resilience factors improve other resilience factors over time. 10.1002/smi.2767
    The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder. Doucet Gaelle E,Bassett Danielle S,Yao Nailin,Glahn David C,Frangou Sophia The American journal of psychiatry OBJECTIVE:Bipolar disorder is a heritable disorder characterized by mood dysregulation associated with brain functional dysconnectivity. Previous research has focused on the detection of risk- and disease-associated dysconnectivity in individuals with bipolar disorder and their first-degree relatives. The present study seeks to identify adaptive brain connectivity features associated with resilience, defined here as avoidance of illness or delayed illness onset in unaffected siblings of patients with bipolar disorder. METHOD:Graph theoretical methods were used to examine global and regional brain network topology in head-motion-corrected resting-state functional MRI data acquired from 78 patients with bipolar disorder, 64 unaffected siblings, and 41 healthy volunteers. RESULTS:Global network properties were preserved in patients and their siblings while both groups showed reductions in the cohesiveness of the sensorimotor network. In the patient group, these sensorimotor network abnormalities were coupled with reduced integration of core default mode network regions in the ventromedial cortex and hippocampus. Conversely, integration of the default mode network was increased in the sibling group compared with both the patient group and the healthy volunteer group. CONCLUSIONS:The authors found that trait-related vulnerability to bipolar disorder was associated with reduced resting-state cohesiveness of the sensorimotor network in patients with bipolar disorder. However, integration of the default mode network emerged as a key feature differentiating disease expression and resilience between the patients and their siblings. This is indicative of the presence of neural mechanisms that may promote resilience, or at least delay illness onset. 10.1176/appi.ajp.2017.17010095
    Studying the predictive factors of suicide attempts in patients with type 1 bipolar disorder. Mazaheri Maryam,Gharraee Banafsheh,Shabani Amir,Lotfi Mozhgan Psychiatry research Bipolar disorder has the highest suicide attempt rate among psychiatric disorders. Many factors are associated with the risk of suicide attempt in patients with type 1 bipolar disorder, but the relation between them has still not been explicitly stated. This study aimed to examine the predictability of suicide attempt risk in BID patients based on quality of life, stressful life events, comorbidity of axis I disorders and medication compliance. We selected 140 inpatients with type 1 bipolar disorder by convenient sampling. Then they completed the WHOQOL-BREF questionnaire, Paykel's stressful life events scale and the medication adherence report scale (MARS). Logistic regression analysis showed that bipolar patients with axis I comorbidity are 40 times more likely to attempt suicide than those without axis I comorbidity. The higher the patients' quality of life, the lower the chance of attempt of suicide. Higher medication compliance reduces the likelihood of suicidal attempt in these patients. And, the increase of stressful life events would raise the risk of suicide attempts, but the relationship wasn't significant. So it can be concluded that quality of life, stressful life events and axis I comorbidity can predict the risk of suicide attempts in patients with type 1 bipolar disorder. 10.1016/j.psychres.2019.04.012
    Undiagnosed bipolar disorder in patients treated for major depression in China. Hu Chen,Xiang Yu-Tao,Ungvari Gabor S,Dickerson Faith B,Kilbourne Amy M,Si Tian-Mei,Fang Yi-Ru,Lu Zheng,Yang Hai-Chen,Chiu Helen F K,Lai Kelly Y C,Hu Jian,Chen Zhi-Yu,Huang Yi,Sun Jing,Wang Xiao-Ping,Li Hui-Chun,Zhang Jin-Bei,Wang Gang Journal of affective disorders BACKGROUND:Bipolar disorder (BD) is a recurrent, complex illness and often misdiagnosed and treated as a major depressive disorder (MDD). This study set out (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV diagnostic criteria; (2) to test the usefulness of the screening tool - the 32-item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether MDD patients with subthreshold manic features (patients who screened positive for BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as measured by Mini International Neuropsychiatric Interview (MINI)) differ from those with BD, and from those suffering from MDD without manic features in terms of basic demographic and clinical variables. METHODS:A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The HCL-32 was self-completed by patients to identify hypomanic symptoms, and the MINI was used by clinicians to establish DSM-IV diagnoses. RESULTS:The proportions of undiagnosed BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL-32 had low positive predictive value (0.43). Compared to MDD patients without subthreshold manic features, MDD patients with subthreshold manic features were younger at onset, less likely to be married and had more depressive episodes on a seasonal basis, and more frequent depressive episodes overall. Compared to BD patients, MDD patients with subthreshold manic features had an older age at onset and less frequent depressive episodes and less family history of psychiatric disorders, appetite, weight gain and time spent sleeping, suicide ideation and attempts and psychotic symptoms. CONCLUSIONS:At least one fifth of Chinese patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to identify broader subthreshold bipolar features. The findings need to be confirmed by longitudinal studies using more comprehensive, standardized instruments. 10.1016/j.jad.2012.02.014
    Suicide risk in major affective disorder: results from a national survey in China. Chen Lin,Liu Yan-Hong,Zheng Qi-Wen,Xiang Yu-Tao,Duan Yan-Ping,Yang Fu-de,Wang Gang,Fang Yi-Ru,Lu Zheng,Yang Hai-Chen,Hu Jian,Chen Zhi-Yu,Huang Yi,Sun Jing,Wang Xiao-Ping,Li Hui-Chun,Zhang Jin-Bei,Chen Da-Fang,Si Tian-Mei Journal of affective disorders BACKGROUND:This study investigated suicide risk and its correlates among major affective disorder patients in China and examined possible risk factors for future suicide among individuals with major affective disorder to inform appropriate interventions and management approaches to minimize and prevent suicide. METHODS:A total of 1478 major affective disorder patients were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI), and suicide risk was assessed by the suicide risk module of the MINI. RESULTS:Of the patients, 963 (65.2%) were in the nonsuicidal risk group and 515 (34.8%) were in the suicidal risk group. Compared to major depressive disorder patients, bipolar disorder patients had higher suicide risk levels (χ2=10.0, df=1, P=0.002); however, there were no statistically significant differences (χ2=2.6, df=1, P=0.1) between bipolar disorder-I and bipolar disorder-II patients. Suicide risk factors were associated with 6 variables in major affective disorder patients, as follows: male gender, unemployed, more frequent depressive episodes (>4 in the past year), depressive episodes with suicidal ideation and attempts, depressive episodes with psychotic symptoms, and no current antidepressant use. LIMITATIONS:Most of the data were retrospectively collected and, therefore, subject to recall bias. CONCLUSIONS:This study suggested that bipolar disorder patients have a higher suicide risk than major depressive disorder patients. The factors that were significantly associated with suicide risk may aid in identifying major affective disorder patients who are at risk for future suicidal behavior. 10.1016/j.jad.2013.10.046
    A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. Zhan Yanni,Zhang Bin,Zhou Yanling,Zheng Wei,Liu Weijian,Wang Chengyu,Li Hanqiu,Chen LiJian,Yu Lin,Walter Martin,Li Meng,Li Ming D,Ning Yuping Journal of affective disorders BACKGROUND:Suicide is a tremendous public health crisis and is demanded urgent intervention. Previous studies found that ketamine intervention could rapidly reduce suicidal ideation in depression. However, the comparatively study in Chinese population remains absence. The current study aims to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal patients, especially distinguish between low suicidal ideation (SI) group and high SI group. METHODS:Eighty-six unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) and Beck Scale for Suicide Ideation (SSI) was measured at baseline, 4 h and 24 h after each infusion, and two-week naturalistically follow-up. RESULTS:Forty-nine (57.0%) patients relief of suicidal ideation after first infusion and 56 (65.1%) after six infusions. Anti-suicidal response rate in low SI group were higher than high SI group, and anti-suicidal response at 4 h after first infusion was significant predictor of response at 24 h after sixth infusion. Furthermore, at 24 h after the sixth infusion, correlation between changes in suicidal ideation and depression was 0.23, accounting for 7.4% in the variance of suicidal ideation change. LIMITATION:The major limitation of this study was that lack of a placebo or other control group limits the interpretation of efficacy. CONCLUSIONS:We confirmed that six repeated ketamine infusions for Chinese suicidal depressed patients were effective in generating a rapid response of suicidal ideation, especially low SI achieved more benefits from ketamine infusions. 10.1016/j.jad.2019.03.071
    White matter abnormalities of corpus callosum in patients with bipolar disorder and suicidal ideation. Annals of general psychiatry OBJECTIVE:Although many studies have shown that the corpus callosum (CC) may play an important role in bipolar disorder (BD) and suicide, the pathophysiological mechanism of BD underlying suicidal behavior is still unclear. This study aimed to explore the relationship between the CC, and BD and suicidal ideation using diffusion tensor imaging (DTI). METHOD:A total of 203 participants (47 BD patients with suicidal ideation, 59 with BD without suicidal ideation, and 97 healthy controls [HC]) underwent DTI scanning at a single site. We examined the white matter integrity of the CC in the three groups. RESULTS:A comparison among groups showed that BD patients with suicidal ideation had significant lower fractional anisotropy (FA) values than those of BD without suicidal ideation and HCs in the body and genu of the CC, and FA values of BD without suicidal ideation were significantly lower than those of HCs. However, in the splenium of corpus callosum, no difference was found between BD without suicidal ideation and HCs. CONCLUSIONS:Our findings add to the evidence suggesting that the CC plays a key role in BD with suicidal ideation, especially with respect to the role of the genu and body of the CC subserving emotion regulation. 10.1186/s12991-019-0243-5
    Childhood traumas in euthymic bipolar disorder patients in Eastern Turkey and its relations with suicide risk and aggression. Adigüzel Vesile,Özdemir Nurgül,Şahin Şengül Kocamer Nordic journal of psychiatry The aim of this study was to determine the relationship between childhood trauma and aggression-suicidal behavior in patients with bipolar disorder. A total of 112 outpatients diagnosed with bipolar disorder in remission in the province of Siirt on the east coast of Turkey were included in this study carried out between January and June 2018. Personal Information Form, Childhood Trauma Questionnaire (CTQ), Buss-Perry Aggression Scale (BPAS) and Suicide Probability Scale (SPS) were used for data acquisition. It was determined that patients with bipolar disorder have 89.3% of physical neglect, 74.1% of emotional neglect, 75.9% of physical abuse, 79.5% of emotional abuse and 40.2% of sexual abuse. The mean score of CTQ was 66.8 ± 19.2, the total score of BPAS was 94.6 ± 28.8 and the total score of SPS was 85.3 ± 17.9. A statistically significant and positive correlation was determined between CTQ, BPAS and SPS ( < 0.05). There was a weak and positive relationship between BPAS, CTQ ( = 0.325**; p < 0.05) and subscales of CTQ which are emotional abuse ( = 0.350**;  < 0.05), physical abuse ( = 0.354**;  < 0.01), physical neglect ( = 0.313**;  < 0.01) and emotional neglect ( = 0.316**;  < 0.01). A statistically significant difference was observed between the regular use of drugs, violence against others and total score of CTQ, BPAS and SPS ( < 0.05). It is suggested that patients diagnosed with bipolar disorder should be evaluated with regards to childhood trauma history by taking into consideration sociodemographic characteristics and psychiatric support in order to prevent their aggression and suicide attempts. 10.1080/08039488.2019.1655589
    Prevalence of childhood trauma and correlations between childhood trauma, suicidal ideation, and social support in patients with depression, bipolar disorder, and schizophrenia in southern China. Xie Peng,Wu Kai,Zheng Yingjun,Guo Yangbo,Yang Yuling,He Jianfei,Ding Yi,Peng Hongjun Journal of affective disorders BACKGROUND:Childhood trauma has long-term adverse effects on physical and psychological health. Previous studies demonstrated that suicide and mental disorders were related to childhood trauma. In China, there is insufficient research available on childhood trauma in patients with mental disorders. METHODS:Outpatients were recruited from a psychiatric hospital in southern China, and controls were recruited from local communities. The demographic questionnaire, the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Social Support Rating Scale (SSRS) were completed by all participants, and the Self-rating Idea of Suicide Scale (SIOSS) were completed only by patients. Prevalence rates of childhood trauma were calculated. Kruskal-Wallis test and Dunnett test were used to compare CTQ-SF and SSRS scores between groups. Logistic regression was used to control demographic characteristics and examine relationships between diagnosis and CTQ-SF and SSRS scores. Spearman's rank correlation test was conducted to analyze relationships between suicidal ideation and childhood trauma and suicidal ideation and social support. RESULTS:The final sample comprised 229 patients with depression, 102 patients with bipolar, 216 patient with schizophrenia, and 132 healthy controls. In our sample, 55.5% of the patients with depression, 61.8% of the patients with bipolar disorder, 47.2% of the patients with schizophrenia, and 20.5% of the healthy people reported at least one type of trauma. In patient groups, physical neglect (PN) and emotional neglect (EN) were most reported, and sexual abuse (SA) and physical abuse (PA) were least reported. CTQ-SF and SSRS total scores, and most of their subscale scores in patient groups were significantly different from the control group. After controlling demographic characteristics, mental disorders were associated with higher CTQ-SF scores and lower SSRS scores. CTQ-SF scores and number of trauma types were positively correlated with the SIOSS score. Negative correlations existed between SSRS scores and the SIOSS score. LIMITATIONS:Our sample may not be sufficiently representative. Some results might have been interfered by demographic characteristics. The SIOSS was not completed by controls. Data from self-report scales were not sufficiently objective. CONCLUSIONS:In southern China, childhood trauma is more severe and more prevalent in patients with mental disorders (depression, bipolar disorder and schizophrenia) than healthy people. Among patients with mental disorders in southern China, suicidal ideation is associated with childhood trauma and poor social support. 10.1016/j.jad.2017.11.011
    Psychotic symptoms and suicidal ideation in child and adolescent bipolar I disorder. Duffy Mary E,Gai Anna R,Rogers Megan L,Joiner Thomas E,Luby Joan L,Joshi Paramjit T,Wagner Karen D,Emslie Graham J,Walkup John T,Axelson David Bipolar disorders OBJECTIVES:The purpose of this study was to explore associations between specific types of hallucinations and delusions and suicidal ideation in a sample of children and adolescents with bipolar I disorder. METHODS:Participants (N = 379) were children and adolescents aged 6-15 years (M = 10.2, SD = 2.7) with DSM-IV diagnoses of bipolar I disorder, mixed or manic phase. The study sample was 53.8% female and primarily White (73.6% White, 17.9% Black, and 8.5% Other). Presence and nature of psychotic symptoms, suicidal ideation, and functioning level were assessed through clinician-administered measures. A series of logistic regressions was performed to assess the contribution of each subtype of psychotic symptom to the presence of suicidal ideation above and beyond age, sex, socio-economic status, age at bipolar disorder onset, and global level of functioning. RESULTS:Hallucinations overall, delusions of guilt, and number of different psychotic symptom types were uniquely associated with increased odds of suicidal ideation after accounting for covariates. Other forms of delusions (eg, grandiose) and specific types of hallucinations (eg, auditory) were not significantly uniquely associated with the presence of suicidal ideation. CONCLUSIONS:Findings of this study suggest the presence of hallucinations as a whole, delusions of guilt specifically, and having multiple concurrent types of psychotic symptoms are associated with the presence of suicidal ideation in children and adolescents with bipolar I disorder. Psychotic symptom subtypes, as opposed to psychosis as a whole, are an under-examined, potentially important, area for consideration regarding suicidal ideation in pediatric bipolar I disorder. 10.1111/bdi.12789
    Sexual and Religious Obsessions in Relation to Suicidal Ideation in Bipolar Disorder. Abdel Hamid Ahmed A L,Nasreldin Mohamed,Gohar Sherif M,Saleh Alia A,Tarek Mennat-Allah Suicide & life-threatening behavior OBJECTIVES:Obsessions and suicidal behavior are common among patients with bipolar disorder. The relation between them and their impact on disease severity should be a focus of attention. This study aimed at assessment of the presence of sexual and religious obsessions in patients with bipolar disorder and their relation to suicide ideation. METHODS:Ninety patients diagnosed with bipolar I disorder were recruited consecutively and subdivided into two groups: bipolar disorder with and without sexual/religious obsessions. Both groups were subjected to Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD), and Beck Scale for Suicide Ideation (BSSI). RESULTS:Patients with bipolar disorder and sexual/religious obsessions were 54.4% (n = 49) of the total sample, and they showed significantly higher number of suicidal attempts, more severe depression, and suicidal ideation than those without sexual/religious obsessions. BSSI showed significantly positive correlation with HAMD and DY-BOCS sexual and religious obsessions dimension-related distress. CONCLUSION:Sexual and religious obsessions tend to be more frequent among patients with bipolar disorder. Higher depression and obsessive-related distress potentially contribute to the increased risk of suicidal ideation. 10.1111/sltb.12540
    Cognitive and family correlates of current suicidal ideation in children with bipolar disorder. Weinstein Sally M,Van Meter Anna,Katz Andrea C,Peters Amy T,West Amy E Journal of affective disorders BACKGROUND:Suicidality among youth with bipolar disorder is an extreme, but largely unaddressed, public health problem. The current study examined the psychosocial characteristics differentiating youth with varying severities of suicidal ideation that may dictate targets for suicide prevention interventions. METHODS:Participants included 72 youth aged 7-13 (M=9.19, SD=1.61) with DSM-IV-TR bipolar I, II, or NOS and a parent/caregiver. Current suicidal ideation and correlates were assessed at intake, including: demographics and clinical factors (diagnosis, symptom severity, psychiatric comorbidity); child factors (cognitive risk and quality of life); and family factors (parenting stress, family cohesion, and family rigidity). RESULTS:Current ideation was prevalent in this young sample: 41% endorsed any ideation, and 31% endorsed active forms. Depression symptoms, quality of life, hopelessness, self-esteem, and family rigidity differentiated youth with increasing ideation severity. Separate logistic regressions examined all significant child- and family-level factors, controlling for demographic and clinical variables. Greater family rigidity and lower self-esteem remained significant predictors of current planful ideation. Diagnosis, index episode, comorbidity, and mania severity did not differentiate non-ideators from those with current ideation. LIMITATIONS:Limitations include the small sample to examine low base-rate severe ideation, cross-sectional analyses and generalizability of findings beyond the outpatient clinical sample. CONCLUSIONS:Findings underscore the importance of assessing and addressing suicidality in preadolescent youth with bipolar disorder, before youth progress to more severe suicidal behaviors. Results also highlight child self-esteem and family rigidity as key treatment targets to reduce suicide risk in pediatric bipolar disorder. 10.1016/j.jad.2014.10.058
    Correlation Between Insight Level and Suicidal Behavior/Ideation in Bipolar Depression. de Assis da Silva Rafael,Mograbi Daniel C,Bifano Jaqueline,Santana Cristina M T,Cheniaux Elie The Psychiatric quarterly Suicide is a relatively common outcome along the course of bipolar disorder. Studies have shown a positive correlation between ideation or attempts of suicide and higher insight in schizophrenic patients. Nevertheless there are still few studies that evaluate the relationship between suicide and insight in mood disorders. Evaluate the relationship between insight and suicidal ideation or behavior in bipolar depression. A group of 165 bipolar patients were followed up along 1 year. Each patient's mood was assessed in every consultation according to DSM-IV-TR criteria. Suicidal ideation and behavior were prospectively assessed through item 3 of HAM-D whenever a major depressive episode was diagnosed. Insight was evaluated through the Insight Scale for Affective Disorders. A history of suicidal attempts was associated with worse insight in 60 patients with one episode of bipolar depression. The difference remained even when the supposed effect of depression over insight was controlled. No correlation between current suicidal ideation and insight level was found though. Our results suggest that a history of suicide attempts may correlate with higher impairment of insight in bipolar depression. No relationship was found between current suicidal ideation and insight. 10.1007/s11126-016-9432-4
    Predictors of suicide ideation among older adults with bipolar disorder. O'Rourke Norm,Heisel Marnin J,Canham Sarah L,Sixsmith Andrew, PloS one OBJECTIVES:Bipolar disorder (BD) carries the greatest risk of death by suicide of all psychiatric conditions as 25%-50% of those with BD will make one or more suicide attempt, and about 15% will intentionally end their lives. Among young adults with BD, substance misuse, medication non-adherence, age at onset, and comorbid psychiatric conditions each predict self-harm. It is currently unclear if these same factors or others predict suicide ideation among older adults with BD. METHODS:We recruited a global sample of 220 older adults with BD over 19 days using socio-demographically targeted, social media advertising and online data collection (Mean = 58.50, SD = 5.42; range 50 to 81 years). Path analyses allowed us to identify direct and indirect predictors of suicide ideation among older adults with BD. RESULTS:Cognitive failures (perception, memory, and motor function), depressive symptoms, alcohol misuse, and dissatisfaction with life as direct predictors of suicide ideation; duration of BD symptoms and medication non-adherence emerged as indirect predictors. Of note, the significant impact of sleep on suicide ideation is indirect via depressive symptoms, cognitive failures, medication non-adherence and life dissatisfaction. CONCLUSIONS:As with young adults with BD, alcohol misuse and medication non-adherence emerged as significant predictors of suicide ideation. In addition, cognitive failures directly and indirectly predict suicide ideation in this sample of older adults with BD. Population aging and treatment efficacy are leading to ever growing numbers of older adults with BD. Both direct and indirect predictors of suicide ideation need to be considered in future BD research and treatment planning. 10.1371/journal.pone.0187632
    Apathy and suicide-related ideation 3 months after stroke: a cross-sectional study. Tang Wai Kwong,Caeiro Lara,Lau Chieh Grace,Liang Huajun,Mok Vincent,Ungvari Gabor S,Wong Ka Sing BMC neurology BACKGROUND:Both apathy and suicide are common in poststroke patients. However, the association between poststroke apathy and suicide-related ideation (SI) in Chinese stroke patients is not clear and poorly understood. The aim of this study was to examine the association between apathy and SI in stroke. METHODS:A cross-sectional study was conducted to investigate the association in 518 stroke survivors from Acute Stroke Unit of the Prince of Wales Hospital in Hong Kong. Geriatric Mental State Examination-Version A (GMS) and Neuropsychiatric Inventory-apathy subscale (NPI-apathy) were employed to assess poststroke SI and apathy, respectively. Patients' clinical characteristics were obtained with the following scales: the National Institutes of Health Stroke Scale (NIHSS), the Mini-Mental State Examination (MMSE), and the Geriatric Depression Scale (GDS). RESULTS:Thirty-two (6.2%) stroke survivors reported SI. The SI group had a significantly higher frequency of NPI-apathy than the non-SI group (31.2% vs 5.3%, p < 0.001). The SI group also had higher GDS scores (10.47 ± 3.17 vs 4.24 ± 3.71, p < 0.001). Regression analysis revealed that NPI-apathy (OR 2.955, 95% CI 1.142-7.647, p = 0.025) was a significant predictor of SI. The GDS score also predicted SI (OR 1.436, 95% CI 1.284-1.606, p < 0.001). CONCLUSIONS:The current findings show that poststroke apathy is an independent predictor of SI 3 months after stroke. Early screening for and intervention targeting apathy through medication and psychological treatments may be necessary to improve stroke patients' apathy and reduce SI. 10.1186/s12883-015-0323-3
    Factors that contribute to psychological resilience to suicidal thoughts and behaviours in people with schizophrenia diagnoses: qualitative study. Harris Kamelia,Gooding Patricia,Haddock Gillian,Peters Sarah BJPsych open BACKGROUND:Suicide is a leading cause of premature death in people with a diagnosis of schizophrenia. Although exposure to stressors can play a part in the pathways to death by suicide, there is evidence that some people with a diagnosis of schizophrenia can be resilient to the impact of suicide triggers. AIMS:To investigate factors that contribute to psychological resilience to suicidal thoughts and behaviours from the perspectives of people with a diagnosis of schizophrenia. METHOD:A qualitative design was used, involving semi-structured, face-to-face interviews. Twenty individuals with non-affective psychosis or schizophrenia diagnoses who had experience of suicide thoughts and behaviours participated in the study. The interviews were audio-recorded, transcribed verbatim and examined using inductive thematic analysis. RESULTS:Participants reported that psychological resilience to suicidal thoughts and behaviours involved ongoing effort. This ongoing effort encompassed: (a) understanding experiences (including reconciliation to mental health experiences and seeking reasons to live), (b) active behaviours (including talking to people and keeping occupied), and (c) relationship dynamics (including feeling supported by significant others and mental health professionals). CONCLUSIONS:Psychological resilience was described as a dynamic process that developed over time through the experiences of psychosis and the concomitant suicidal experiences. Psychological resilience can be understood using a multicomponential, dynamic approach that integrates buffering, recovery and maintenance resilience models. In order to nurture psychological resilience, interventions should focus on supporting the understanding and management of psychosis symptoms and concomitant suicidal experiences. DECLARATION OF INTEREST:None. 10.1192/bjo.2019.63
    The Reciprocal Relationship between Bipolar Disorder and Social Interaction: A Qualitative Investigation. Owen Rebecca,Gooding Patricia,Dempsey Robert,Jones Steven Clinical psychology & psychotherapy BACKGROUND:Evidence suggests that social support can influence relapse rates, functioning and various clinical outcomes in people with bipolar disorder. Yet 'social support' is a poorly defined construct, and the mechanisms by which it affects illness course in bipolar disorder remain largely unknown. Key aims of this study were to ascertain which facets of social interaction affect mood management in bipolar disorder, and how symptoms of bipolar disorder can influence the level of support received. METHOD:Semi-structured qualitative interviews were conducted with 20 individuals with bipolar disorder. Questions were designed to elicit: the effects of social interaction upon the management and course of bipolar disorder; and the impact of bipolar disorder upon social relationships. An inductive thematic analysis was used to analyse the data. RESULTS:Empathy and understanding from another person can make it easier to cope with bipolar disorder. Social interaction can also provide opportunities to challenge negative ruminative thoughts and prevent the onset of a major mood episode. The loss of social support, particularly through bereavement, creates a loss of control and can trigger mania or depression. Hypomanic symptoms can facilitate new social connections, whereas disinhibited and risky behaviour exhibited during mania can cause the breakdown of vital relationships. CONCLUSIONS:An in-depth clinical formulation of an individual's perceptions of how their illness affects and is affected by social interaction is crucial to understanding psychosocial factors which influence mood management. These results have clear application in interventions which aim to promote improved wellbeing and social functioning in bipolar disorder. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONERS MESSAGES:The relationship between bipolar-related experiences and social interaction is complex and multi-faceted. Bipolar disorder can damage social relationships and create a loss of social control via extreme mood states, but it can also offer a social advantage through elevated self-confidence during hypomania and enhanced resilience post-recovery. Positive social experiences can facilitate better personal coping and enhanced mood management, whilst negative social experiences can trigger the onset of acute mood episodes. A comprehensive formulation of the reciprocal links between facets of bipolar disorder and characteristics of interpersonal relationships should be used to guide psychosocial interventions that aim to enhance emotion regulation and improve functioning. 10.1002/cpp.2055
    Positive aspects of mental illness: a review in bipolar disorder. Galvez Juan Francisco,Thommi Sairah,Ghaemi S Nassir Journal of affective disorders INTRODUCTION:There is growing interest to understand the role of positive psychological features on the outcomes of medical illnesses. Unfortunately this topic is less studied in relation to mental health, and almost completely neglected in relation to one of the most common severe psychiatric illnesses, bipolar disorder. Certain specific psychological characteristics, that are generally viewed as valuable and beneficial morally or socially, may grow out of the experience of having this affective disorder. OBJECTIVE:We describe the sources, research and impact of these positive psychological traits in the lives of persons with bipolar disorder based on the few published literature available to date. These include, but are not limited to: spirituality, empathy, creativity, realism, and resilience. METHODS:After an extensive search in the literature, we found 81 articles that involve descriptions of positive psychological characteristics of bipolar disorder. RESULTS:We found evidence for enhancement of the five above positive psychological traits in persons with bipolar disorder. CONCLUSIONS:Bipolar disorder is associated with the positive psychological traits of spirituality, empathy, creativity, realism, and resilience. Clinical and research attention to preserving and enhancing these traits may improve outcomes in bipolar disorder. 10.1016/j.jad.2010.03.017
    Decreased empathy response to other people's pain in bipolar disorder: evidence from an event-related potential study. Yang Jingyue,Hu Xinglong,Li Xiaosi,Zhang Lei,Dong Yi,Li Xiang,Zhu Chunyan,Xie Wen,Mu Jingjing,Yuan Su,Chen Jie,Chen Fangfang,Yu Fengqiong,Wang Kai Scientific reports Bipolar disorder (BD) patients often demonstrate poor socialization that may stem from a lower capacity for empathy. We examined the associated neurophysiological abnormalities by comparing event-related potentials (ERP) between 30 BD patients in different states and 23 healthy controls (HCs, matched for age, sex, and education) during a pain empathy task. Subjects were presented pictures depicting pain or neutral images and asked to judge whether the person shown felt pain (pain task) and to identify the affected side (laterality task) during ERP recording. Amplitude of pain-empathy related P3 (450-550 ms) of patients versus HCs was reduced in painful but not neutral conditions in occipital areas [(mean (95% confidence interval), BD vs. HCs: 4.260 (2.927, 5.594) vs. 6.396 (4.868, 7.924)] only in pain task. Similarly, P3 (550-650 ms) was reduced in central areas [4.305 (3.029, 5.581) vs. 6.611 (5.149, 8.073)]. Current source density in anterior cingulate cortex differed between pain-depicting and neutral conditions in HCs but not patients. Manic severity was negatively correlated with P3 difference waves (pain - neutral) in frontal and central areas (Pearson r = -0.497, P = 0.005; r = -0.377, P = 0.040). Electrophysiological correlates of empathy processing are reduced in BD depending on manic symptom severity. 10.1038/srep39903
    Social and nonsocial cognition in bipolar disorder and schizophrenia: relative levels of impairment. Lee Junghee,Altshuler Lori,Glahn David C,Miklowitz David J,Ochsner Kevin,Green Michael F The American journal of psychiatry OBJECTIVE:This study aimed to determine the relative extent of impairment in social and nonsocial cognitive domains in patients with bipolar disorder compared with schizophrenia patients and healthy comparison subjects. METHODS:Sixty-eight clinically stable outpatients with bipolar disorder, 38 clinically stable outpatients with schizophrenia, and 36 healthy comparison subjects completed a range of social (facial affect perception, emotional regulation, empathic accuracy, mental state attribution, and self-referential memory) and nonsocial (speed of processing, attention/vigilance, working memory, verbal memory, visual memory, and reasoning/problem solving) cognitive tasks. RESULTS:For each social cognitive task, patients with bipolar disorder did not differ significantly from comparison subjects, and both groups performed better than schizophrenia patients. Within the bipolar group, clinical features and medication status were not related to social cognitive performance. Bipolar patients showed performance patterns across tasks (i.e., profiles) that were similar to those of comparison subjects on both social and nonsocial cognitive domains, whereas both groups differed from schizophrenia patients for both domains. Regarding relative impairment across the two cognitive domains, results revealed a significant group-by-domain interaction in which bipolar patients showed less impaired social than nonsocial cognition, while schizophrenia patients showed the opposite pattern. CONCLUSIONS:Bipolar patients showed less impairment on social relative to nonsocial cognitive performance, whereas schizophrenia patients showed more impairment on social relative to nonsocial cognitive performance. These results suggest that these two cognitive domains play different roles in bipolar disorder compared with in schizophrenia. 10.1176/appi.ajp.2012.12040490
    Improvement in cognitive function in young people with bipolar disorder: Results from participants in an 18-month randomised controlled trial of adjunctive psychotherapy. Porter Richard J,Inder Maree,Douglas Katie M,Moor Stephanie,Carter Janet D,Frampton Christopher Ma,Crowe Marie The Australian and New Zealand journal of psychiatry OBJECTIVE:To examine the effects of 18 months of intensive stabilisation with medication management and Interpersonal and Social Rhythm Therapy or Non-specific Supportive Clinical Management on cognitive function in young people with bipolar disorder. Determinants of change in cognitive function over the 18 months of the trial were also examined. METHOD:Patients aged 15-36 years with Bipolar I Disorder, Bipolar II Disorder and Bipolar Not Otherwise Specified were recruited. From a battery of cognitive tests, change scores for pre-defined domains of cognitive function were created based on performance at baseline and follow-up. Change was compared between the two therapy groups. Regression analysis was used to determine the impact of a range of clinical variables on change in cognitive performance between baseline and follow-up. RESULTS:One hundred participants were randomised to Interpersonal and Social Rhythm Therapy ( = 49) or Non-specific Supportive Clinical Management ( = 51). Seventy-eight patients underwent cognitive testing at baseline and 18 months. Across both groups, there were significant improvements in a Global Cognitive Composite score, Executive Function and Psychomotor Speed domains from baseline to 18 months. Lower scores at baseline on all domains were associated with greater improvement over 18 months. Overall, there was no difference between therapies in change in cognitive function, either in a global composite score or change in domains. CONCLUSION:While there was no difference between therapy groups, intensive stabilisation with psychological therapy was associated with improved cognitive function, particularly in those patients with poorer cognitive function at baseline. However, this was not compared with treatment as usual so cannot be attributed necessarily to the therapies. 10.1177/0004867419887794
    Men and women with psychosis and the impact of illness-duration on sex-differences: The second Australian national survey of psychosis. Hanlon Mary-Claire,Campbell Linda E,Single Natalie,Coleman Clare,Morgan Vera A,Cotton Susan M,Stain Helen J,Castle David J Psychiatry research We aimed to examine and compare sex-differences in people receiving treatment for psychotic illnesses in community settings, based on long or short duration of illness; expecting association between longer illness-duration and worse outcomes in women and men. Clinical, demographic and service-use data from the Survey of High Impact Psychosis were analysed by sex and duration of illness (≤5 years; ≥6 years), using independent t-tests, chi-square tests, one-way ANOVA, and Cramer's V. Of the 1825 participants, 47% had schizophrenia, 17.5% bipolar and 16.1% schizo-affective disorders. More women than men had undertaken post-school education, maintained relationships, and been living in their own homes. Women with a shorter-illness-duration showed social functioning equivalent to non-ill women in the general population. Men tended to have an early illness onset, show premorbid dysfunction, be single, show severe disability, and to use illicit substances. Men with a longer-illness-duration were very socially disadvantaged and isolated, often experiencing homelessness and substance use. Men with a short-illness-duration were most likely to be in paid employment, but two-thirds earned less than $AUD500 per fortnight. Men with longer-illness-duration showed most disability, socially and globally. Interventions should be guided by diagnosis, but also by a person's sex and duration of illness. 10.1016/j.psychres.2017.06.024
    The effect of a brief mindfulness-based intervention on personal recovery in people with bipolar disorder: a randomized controlled trial (study protocol). Chan Sunny H W,Tse Samson,Chung K F,Yu C H,Chung Raymond C K,Lo Herman H M BMC psychiatry BACKGROUND:With the advent of the recovery movement in mental health, a humanistic paradigm shift has occurred, placing the focus on personal recovery (i.e., hope, identity, and life meaning) instead of functional or clinical recovery only (i.e., symptom reduction or increases in physical function). Along the journey of recovery, people with bipolar disorder (BD) struggle to cope with recurring mood fluctuations between depression and mania. Mindfulness-based interventions (MBIs) have the potential to result in improvements in personal recovery outcomes. Thus, this protocol will evaluate the efficacy and mechanisms of a brief MBI for helping individuals with BD with their personal recovery. It is hypothesized that adults with BD randomly assigned to a brief MBI intervention will report greater improvements in personal recovery than those in a waiting list control condition. In addition, it is hypothesized that such benefits will be mediated by improvements in emotion awareness, emotion regulation, and illness acceptance. Moreover, the specific stage of BD is hypothesized to moderate the beneficial effects of the brief MBI, such that those in the early stage of BD will report more benefits regarding emotion awareness and emotion regulation, whereas those in the late stage of BD will report more advantages concerning illness acceptance. METHOD:One hundred and fifty-four adults with BD will be recruited from hospitals and community settings for this research project. This study will use a mixed methods design. A randomized-controlled trial will be conducted to compare a brief MBI (four sessions in total) group and a waiting list control group. Assessments will be made at baseline, after intervention, and at six-month follow-up. In addition, a qualitative and participatory research method called Photovoice will be employed to further understand the experiences of the participants who receive the brief MBI along their personal recovery journey. DISCUSSION:If the study hypotheses are supported, the findings from this research project will provide empirical support for an alternative treatment. Moreover, by identifying the mechanisms of the beneficial effects of the brief MBI, the findings will highlight process variables that could be specifically targeted to make MBI treatment even more effective in this population. TRIAL REGISTRATION:This study is registered with the Chinese Clinical Trial Registry ( ChiCTR- 1900024658 ). Registered 20th July 2019. 10.1186/s12888-019-2242-0
    Impact of number of episodes on neurocognitive trajectory in bipolar disorder patients: a 5-year follow-up study. Sánchez-Morla Eva María,López-Villarreal Ana,Jiménez-López Estela,Aparicio Ana Isabel,Martínez-Vizcaíno Vicente,Roberto Rodriguez-Jimenez,Vieta Eduard,Santos José-Luis Psychological medicine BACKGROUND:The neurocognitive trajectory in bipolar disorder (BD) is variable, with controversial findings, and most evidence come from cross-sectional studies. We aimed to examine the course of neurocognitive functioning in a sample of euthymic BD patients in comparison with a control group during a 5-year follow-up. METHODS:Ninety-nine euthymic bipolar patients and 40 healthy controls were assessed using a comprehensive neurocognitive battery (six neurocognitive domains) at baseline (T1) and then at 5-year follow-up (T2) in a longitudinal study. RESULTS:No evidence of a progression in neurocognitive dysfunction was found either in cognitive composite index or in any of the neurocognitive domains for the whole cohort. However, there was a negative correlation between number of manic episodes and hospitalisations due to manic episodes and change in neurocognitive composite index (NCI) during the follow-up. Moreover, patients with higher number of manic and hypomanic episodes have a greater decrease in NCI, working memory and visual memory. History of psychotic symptoms was not related to the trajectory of neurocognitive impairment. CONCLUSIONS:Our results suggest that, although the progression of cognitive decline is not a general rule in BD, BD patients who have a greater number of manic or hypomanic episodes may constitute a subgroup characterised by the progression of neurocognitive impairment. Prevention of manic and hypomanic episodes could have a positive impact on the trajectory of cognitive function. 10.1017/S0033291718001885
    Interpersonal and Social Rhythm Therapy for Patients With Major Depressive Disorder. American journal of psychotherapy OBJECTIVE:This study aimed to conduct a safety analysis among patients with major depressive disorder receiving interpersonal and social rhythm therapy (IPSRT) with and without cognitive remediation. METHODS:This preliminary safety analysis of the outcomes of patients with major depressive disorder was part of a larger randomized controlled trial (RCT) in which patients with bipolar disorder and major depressive disorder received IPSRT; half were randomly assigned to receive additional cognitive remediation. The study focused on patients with major depressive disorder because IPSRT had not been trialed with this group; their outcomes were compared with those of patients with bipolar disorder. Data from the first 30 RCT participants were used to examine whether the intervention had adverse effects, whether mood symptoms and functioning improved over 12 months, and whether there was a signal of benefit. Mood symptoms were measured at baseline and 12 months with the Longitudinal Interval Follow-Up Evaluation and the Quick Inventory of Depressive Symptoms-Self-Reported; functioning was measured with the Social Adjustment Scale. RESULTS:A total of 63% (N=19) of participants were diagnosed with bipolar disorder and 27% (N=11) with major depressive disorder. No adverse effects were found for those with major depressive disorder, and improvements were seen in mean depressive and functioning scores at 12 months compared with baseline, with moderate to large effect sizes. CONCLUSIONS:IPSRT may be a clinically effective intervention for patients with major depressive disorder. Outcomes related to cognitive functioning and the effects of cognitive remediation will be reported at the end of the trial. 10.1176/appi.psychotherapy.20190024
    Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder. Lin Kangguang,Shao Robin,Wang Runhua,Lu Weicong,Zou Wenjin,Chen Kun,Gao Yanling,Brietzke Elisa,McIntyre Roger S,Mansur Rodrigo B,Zhang Li,Yau Suk-Yu,Su Huanxing,Xu Guiyun,So Kwok-Fai Brain, behavior, and immunity Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (P = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (P = 0.021), but not the symptomatic offspring (P > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = -6.0432 to -0.0731) but not the symptomatic offspring (bootstrapping CI = -0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience. 10.1016/j.bbi.2019.10.010
    Predictors of longitudinal psychosocial functioning in bipolar youth transitioning to adults. Hower Heather,Lee Erica J,Jones Richard N,Birmaher Boris,Strober Michael,Goldstein Benjamin I,Merranko John,Keller Martin B,Goldstein Tina R,Weinstock Lauren M,Dickstein Daniel P,Hunt Jeffrey I,Diler Rasim S,Ryan Neal D,Gill Mary Kay,Axelson David,Yen Shirley Journal of affective disorders OBJECTIVES:In a sample of participants diagnosed with Bipolar Disorder (BD) in youth, we aim: (1) to examine longitudinal psychosocial functioning; (2) to determine whether psychosocial impairment remains in those who remitted from mood disorders during later periods of follow-up; (3) to examine predictors of psychosocial impairment despite symptomatic remission. METHOD:A Course and Outcome of Bipolar Youth subsample of 367 (≥ 4 years follow-up data) were grouped into mood trajectories: Class 1 Predominantly Euthymic; Class 2 Moderately Euthymic; Class 3 Ill with Improving Course; Class 4 Predominantly Ill. Psychosocial functioning was assessed via Children's Global Assessment Scale (C-GAS) for those under age 22; Global Assessment of Functioning (GAF) scale after 22. Current school, employment, and disability status were examined. Established predictors of symptomatic impairment were analyzed. RESULTS:The Predominantly Euthymic Class had better psychosocial functioning, and were more likely to be in school/employed. The Persistently Ill Class had worse psychosocial functioning, and were more likely to receive disability. However, 44% of Predominantly Euthymic and 93% of Ill with Improving Course participants continued to experience current psychosocial impairment. Early BD onset, low Socioeconomic Status (SES), and current comorbidity, predicted poor psychosocial functioning. Low SES, and current comorbidity, predicted no school enrollment/unemployment. LIMITATIONS:The study does not have a healthy control group to compare functioning findings. CONCLUSIONS:In general, youth with persistent mood symptoms had worse psychosocial functioning, moreover, those with remitted symptoms still exhibited current psychosocial functioning deficits. High risk individuals with predictors of impairment should be targeted for functioning interventions. 10.1016/j.jad.2018.12.108
    Self-Harm, Affective Traits, and Psychosocial Functioning in Adults With Depressive and Bipolar Disorders. Weintraub Marc J,Van de Loo Margaret M,Gitlin Michael J,Miklowitz David J The Journal of nervous and mental disease Self-harm refers to the purposeful destruction of bodily tissue without suicidal intention and for purposes that are not socially sanctioned. Little is known about the associations between a history of self-harm, mood symptoms, and functioning in adults with different types of mood disorders. Lifetime histories of self-harm, current mood symptoms, global functioning, and affective traits were collected on 142 adults with mood disorders. The prevalence of lifetime self-harm was higher in patients with bipolar disorder compared with patients with a unipolar depressive disorder. Self-harm was also more strongly linked to impulsivity in individuals with bipolar disorder compared with unipolar depressive disorder. Across both diagnoses, histories of self-harm were related to lower levels of current global functioning, more severe depressive symptoms, and high self-reported emotional dysregulation and neuroticism. Findings indicate that self-harm is a potent prognostic variable for symptoms, global functioning, and personality functioning in individuals with mood disorders. 10.1097/NMD.0000000000000744
    Social cognition in bipolar disorder: the role of sociodemographic, clinical, and neurocognitive variables in emotional intelligence. Varo C,Jiménez E,Solé B,Bonnín C M,Torrent C,Lahera G,Benabarre A,Saiz P A,de la Fuente L,Martínez-Arán A,Vieta E,Reinares M Acta psychiatrica Scandinavica OBJECTIVE:The main aims of this study were to examine the differences in the Emotional Intelligence (EI), the emotional domain of social cognition (SC), between euthymic patients with bipolar disorder (BD) and healthy controls (HC) and to evaluate the contribution of sociodemographic, clinical, and neuropsychological variables to EI. METHODS:We recruited 202 patients with BD and 50 HC. EI was evaluated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). The sociodemographic, clinical, and neurocognitive variables that showed a significant association with EI were entered into hierarchical multiple regression analysis. RESULTS:BD patients obtained significantly lower scores compared to HC in the Emotional Intelligence Quotient (EIQ) and in the Understanding Emotions branch score. The best fitting model for the variables associated with EI in the patients group was a linear combination of gender, estimated IQ, family history of affective diagnosis, and executive function. The model, including these previous variables, explained up to 27.6% of the observed variance (R  = 0.276, F = 16.406, P < 0.001). CONCLUSIONS:The identification of variables associated with deficit in EI, such as male gender, lower estimated IQ, family history of affective diagnosis. and lower executive function performance, may help in selecting treatment targets to improve SC, and especially EI, in patients with BD. 10.1111/acps.13014
    Coping with amplified emotionality among people with bipolar disorder: A longitudinal study. Chan Sunny H W,Tse Samson Journal of affective disorders BACKGROUND:The amplified emotionality characteristics of bipolar disorder (BD) may interfere with goal pursuit in the recovery process. This is the first study to test the coping flexibility model empirically among people with BD. Finding ways to cope with goal-striving life events should shed light on managing elevated mood states. METHODS:Using a 12-month longitudinal follow-up design, this study examined the stability in coping flexibility with experimentally-devised Behavioral Approach System (BAS) activating life events and mood states at 6- and 12-month time points for individuals with BD (n = 83) and healthy controls (n = 89). Hierarchical linear modeling tested the individual growth model by studying the longitudinal data. RESULTS:The findings showed fluctuations in different components of coping flexibility and mood states across time. They confirmed the amplified emotionality characteristics of BD. Moreover, coping flexibility took precedence over BAS sensitivity and psychosocial functioning levels in predicting mood states. LIMITATIONS:Measurements of BAS sensitivity may focus on trait nature only and prone to subjective bias. The assessment of mood or coping flexibility may not accurately capture actual experience in daily life. Lack of respective data on bipolar subtypes and significant differences in some dimensions between the BD and control groups are further limitations of the study. CONCLUSIONS:The study's findings have implications for coping with amplified emotionality within the personal recovery process for people with BD. Judicious application of coping strategies and adjustment of perceived controllability are crucial for individuals to reach goals pertinent to personal recovery and manage potential manic mood symptoms. 10.1016/j.jad.2018.07.025
    Theory of mind impairment and its clinical correlates in patients with schizophrenia, major depressive disorder and bipolar disorder. Wang Yan-Yu,Wang Yi,Zou Ying-Min,Ni Ke,Tian Xue,Sun Hong-Wei,Lui Simon S Y,Cheung Eric F C,Suckling John,Chan Raymond C K Schizophrenia research BACKGROUND:Although Theory of Mind (ToM) impairment has been observed in patients with a wide range of mental disorders, the similarity and uniqueness of these deficits across diagnostic groups has not been thoroughly investigated. METHODS:We recruited 35 participants with schizophrenia (SCZ), 35 with bipolar disorder (BD), 35 with major depressive disorder (MDD), and 35 healthy controls in this study. All participants were matched in age, gender proportion and IQ estimates. The Yoni task, capturing both the cognitive and affective components of ToM at the first- and second-order level was administered. Repeated-measure ANOVA and MANOVA were conducted to compare the group differences in ToM performance. A network was then constructed with ToM performances, psychotic and depressive symptoms, and executive function as nodes exploring the clinical correlates of ToM. RESULTS:Overall, ToM impairments were observed in all patient groups compared with healthy controls, with patients with SCZ performing worse than those with BD. In second-order conditions, patients with SCZ and MDD showed deficits in both cognitive and affective conditions, while patients with BD performed significantly poorer in cognitive conditions. Network analysis showed that second-order affective ToM performance was associated with psychotic and depressive symptoms as well as executive dysfunction, while second-order affective ToM performance and negative symptoms showed relatively high centrality in the network. CONCLUSIONS:Patients with SCZ, MDD and BD exhibited different types and severity of impairments in ToM sub-components. Impairment in higher-order affective ToM appears to be closely related to clinical symptoms in both psychotic and affective disorders. 10.1016/j.schres.2017.11.003
    Functional outcome assessment in bipolar disorder: A systematic literature review. Chen Maxine,Fitzgerald Heather M,Madera Jessica J,Tohen Mauricio Bipolar disorders OBJECTIVES:Functional impairment is an important driver of disability in patients with bipolar disorder (BD) and can persist even when symptomatic remission has been achieved. The objectives of this systematic literature review were to identify studies that assessed functioning in patients with BD and describe the functional scales used and their implementation. METHODS:A systematic literature review of English-language articles published between 2000 and 2017 reporting peer-reviewed, original research related to functional assessment in patients with BD was conducted. RESULTS:A total of 40 articles met inclusion criteria. Twenty-four different functional scales were identified, including 13 clinician-rated scales, 7 self-reported scales, and 4 indices based on residential and vocational data. The Global Assessment of Functioning (GAF) and the Functional Assessment Short Test (FAST) were the most commonly used global and domain-specific scales, respectively. All other scales were used in ≤2 studies. Most studies used ≥1 domain-specific scale. The most common applications of functional scales in these studies were evaluations of the relationships between global or domain-specific psychosocial functioning and cognitive functioning (eg, executive function, attention, language, learning, memory) or clinical variables (eg, symptoms, duration of illness, number of hospitalizations, number of episodes). CONCLUSIONS:The results of this review show growing interest in the assessment of functioning in patients with BD, with an emphasis on specific domains such as work/educational, social, family, and cognitive functioning and high utilization of the GAF and FAST scales in published literature. 10.1111/bdi.12775
    Measuring social and occupational functioning of people with bipolar disorder: A systematic review. Akers Nadia,Lobban Fiona,Hilton Claire,Panagaki Katerina,Jones Steven H Clinical psychology review Previous literature has focused on impaired social and occupational functioning in Bipolar Disorder (BD), however this ignores people who may be functioning well or even exceptionally. This paper presents the first systematic review of how functioning is measured and the range of functioning observed in BD to aid applied research and practice in this area. Identified measures from studies reporting use of a social and/or occupational functioning measure in BD were organised according to frequency of use over the last 10 years, resulting in six measures (Global Assessment of Functioning (GAF), Functioning Assessment Short Test (FAST), Social and Occupational Functioning Scale (SOFAS), Social Adjustment Scale (SAS)), Social Functioning Scale (SFS) and LIFE-Range of Impaired Functioning (LIFE-RIFT). Descriptive statistics of sample scores were extracted and pooled to provide cross-study values for each measure. Around 16% of individuals with BD can be estimated to function at a high level, defined as those falling within two standard deviations of the mean score on each measure. Evidence of a ceiling effect for some measures suggests that BD functioning may have been underestimated during measure development. Future research is needed to further understand higher functioning in people with BD, and factors which may support this. 10.1016/j.cpr.2019.101782
    Treatment to Enhance Cognition in Bipolar Disorder (TREC-BD): Efficacy of a Randomized Controlled Trial of Cognitive Remediation Versus Active Control. Lewandowski Kathryn E,Sperry Sarah H,Cohen Bruce M,Norris Lesley A,Fitzmaurice Garrett M,Ongur Dost,Keshavan Matcheri S The Journal of clinical psychiatry OBJECTIVE:Cognitive dysfunction is a core symptom dimension in bipolar disorder and a strong predictor of functional outcomes. Cognitive remediation (CR) produces moderate, durable effects on cognition in patients with schizophrenia; however, studies of CR in patients with bipolar disorder are sparse and findings have been mixed. Thus, the aim of this study was to evaluate the effects of CR versus active control in patients with bipolar disorder with psychosis. METHODS:Patients with a DSM-IV diagnosis of bipolar disorder with psychosis (n = 75) were randomized to a 70-hour computerized CR program or a dose-matched computer control using a parallel design with 1:1 allocation between July 2011 and November 2015. Cognition (primary outcome) and clinical and community functioning (secondary outcomes) were assessed at baseline, at treatment midpoint (after 20-25 hours of training), posttreatment, and at durability (after 6 months of no study contact). Participants and assessment staff were blind to group membership. RESULTS:75 participants were randomly assigned to a treatment group, and 72 participants initiated the active phase of treatment and were included in the primary, intent-to-treat analysis (CR: n = 39; Control: n = 33). Linear mixed effects models examining the effects of CR versus Control at posttreatment showed medium to large effects of CR on processing speed (d = 0.42), visual learning and memory (d = 0.92), and the composite (d = 0.80). Superiority of CR over Control on processing speed (d = 0.65) and composite (d = 0.83) was maintained or increased at durability. CR was not associated with change in community functioning, although cognitive change was associated with functional change across the sample. CONCLUSIONS:Cognitive remediation produced significant improvements over an active control in several cognitive domains and the cognitive composite. While both groups improved on several domains relative to baseline, durability of gains was unique to CR. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01470781. 10.4088/JCP.17m11476
    Functional outcome and social cognition in bipolar disorder: Is there a connection? Vlad Maria,Raucher-Chéné Delphine,Henry Audrey,Kaladjian Arthur European psychiatry : the journal of the Association of European Psychiatrists BACKGROUND:Interest in social cognition in bipolar disorder (BD) has increased considerably over the past decade, with studies highlighting major impairments, especially in mental state reasoning, even during euthymia. A causal relationship between social cognition deficits and social functioning has already been established in individuals with schizophrenia, but there is still little information about links between social cognition and social functioning in BD. Our aim was therefore to review the relationship between functional outcome and social cognition in patients with BD. METHODS:We conducted a systematic review of the literature. Relevant articles were identified through literature searches in the MEDLINE/PubMed, EBSCOHost and Google Scholar databases for the years 2000-2017, using the keywords bipolar, social cognition, theory of mind, mentalizing, emotion recognition, emotion processing, and functioning. A total of 20 studies met our inclusion/exclusion criteria. RESULTS:We found that functioning was significantly correlated with three domains of social cognition (ToM, emotion processing, and attribution bias). Twelve of 13 studies reported a correlation with emotion processing, but a correlation with ToM was only found in three of the 11 studies that assessed it. Six studies found an effect of depressive symptoms on emotion processing and no significant association was found with manic symptomatology. CONCLUSIONS:To the best of our knowledge, the present review is the first to specifically explore the relationship between social cognition and social functioning in patients with BD. This exploration is of interest, as it enhances current understanding of this disorder and, by so doing, should improve patient outcomes. 10.1016/j.eurpsy.2018.05.002
    Living the life you want following a diagnosis of bipolar disorder: A grounded theory approach. Warwick Helen,Tai Sara,Mansell Warren Clinical psychology & psychotherapy Bipolar disorder (BD) is considered a severe and lifelong mental health diagnosis. However, there is growing evidence of people defying the odds and recovering. Processes underlying recovery remain poorly understood. This study aimed to explore these recovery processes and extend on the length of recovery defined within previous research. Twelve people previously diagnosed with BD, who had not experienced an episode of depression and/or mania for four or more years, were interviewed. Standardised diagnostic interviews (Structured Clinical Interview for Diagnostic and Statistical Manual-V, Research version) confirmed past diagnosis and recovery time. Qualitative methodology via grounded theory was used to analyse these personal accounts. The analysis revealed 10 overarching categories of what participants reported to be important in their recovery: support, recognition of the problem, believing that things can change and not giving up, instinctive curiosity, medication, psychological therapy, becoming the director of your own life, changing how I think, accepting who I am and how I feel, and looking after me. A model was developed to represent how categories were related. The study was limited by recruitment not leading to the inclusion of people who had distanced themselves from the label of BD. Potential transdiagnostic recovery processes also require further direct exploration. Critically, the study highlights that following a diagnosis of BD, people do experience long-term recovery achieved through self-determined pathways and that being able to live the life you want is therefore achievable. This challenges current diagnostic perspectives and societal messages of lifelong conditions. 10.1002/cpp.2358
    Prevalence and predictors of physician recommendations for medication adjustment in bipolar disorder treatment. Hodgkin Dominic,Stewart Maureen T,Merrick Elizabeth L,Pogue Ye Zhang,Reilly-Harrington Noreen A,Sylvia Louisa G,Deckersbach Thilo,Nierenberg Andrew A Journal of affective disorders BACKGROUND:Successful medication management for bipolar disorder requires clinicians to monitor and adjust regimens as needed, to achieve maximum effectiveness and patient adherence. This study aims to measure the prevalence of indications for medication adjustment at visits for bipolar disorder treatment; the frequency with which physicians recommend medication adjustments; and how strongly the indications predict the adjustments. METHODS:Data included 3,094 visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that compared treatment with lithium versus quetiapine. A set of indications for adjustment was matched to reports of whether the physician recommended a medication adjustment at that visit, and what type. Associations between indication and adjustment were examined using bivariate tests and hierarchical logistic mixed effects models. RESULTS:Medication adjustment was recommended at 63% of the visits where one of the indications was present, and at 53% of all visits. In multivariable analyses, adjustment was more likely to be recommended if there was an indication of non-response or side effects, for patients who started on quetiapine rather than lithium, or for patients who were female, married, employed or more educated. LIMITATIONS:The study's cross-sectional design implies that observed associations could result from confounding variables. Also, the CHOICE trial placed certain restrictions on physicians' medication choices, although this is not likely to have resulted in major alterations of prescribing patterns. CONCLUSIONS:Clinical inertia may help explain the lack of any adjustment recommendation at 37% of the visits where one of the indications was present. Other explanations could also apply, such as watchful waiting. 10.1016/j.jad.2018.06.012
    Resilience Predicts Social Functioning in Clinically Stable Patients With Bipolar Disorder. Bozikas Vasilis P,Parlapani Eleni,Ntouros Evangelos,Bargiota Stavroula I,Floros Georgios,Nazlidou Elena I,Garyfallos Georgios The Journal of nervous and mental disease The current study focused on the association between resilience and social functioning in patients with bipolar disorder (BD). Forty clinically stable patients with BD type I and BD type II, as well as 40 healthy controls, matched for age, sex, and educational background were enrolled. Clinical status was assessed by the Montgomery-Åsberg Depression Rating Scale and the Young Mania Rating Scale. Functioning was evaluated by the Mini International Classification of Functioning, Disability and Health rating of activities and participation in mental illnesses, and the Social and Occupational Functioning Scale. Resilience was measured by the Connor-Davidson Resilience scale. Patients demonstrated significantly lower resilience levels compared with healthy individuals. A stepwise regression analysis indicated that only resilience contributed significantly to social functioning's outcome. Because resilience may constitute a social functioning moderator in clinically stable patients with BD, a paradigm shift toward protective factors could lead to implementation of resilience-oriented interventions designed specifically for patients with BD. 10.1097/NMD.0000000000000843
    Social cognition and interaction training (SCIT) for partially remitted patients with bipolar disorder in China. Zhang Yong,Ma Xiaojuan,Liang Sixiang,Yu Wenwen,He Qianqian,Zhang Jian,Bian Yanhui Psychiatry research Bipolar disorder (BD) is associated with functional impairment. Social Cognition and Interaction Training (SCIT) has been shown to be feasible and effective at improving social functioning in patients with schizophrenia. We aimed to explore the association between SCIT and improvements in the clinical symptoms and functioning of partially remitted patients with BD in China. Seventy-four BD patients were randomly assigned to the SCIT and psychoeducation (Control) groups. All subjects participated in group interventions weekly for 8 weeks. Furthermore, the participants were administered the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS-17), the Function Assessment Short Test (FAST) and neurocognitive measures at baseline and after eight weeks. There were no differences in demographics, the HDRS-17, YRMS, and FAST scores or neurocognitive measures between the groups at baseline (p>0.05). The repeated-measures analysis revealed that SCIT resulted in greater improvement in the HDRS, YMRS, and FAST scores (including six domains) (p<0.01) and two neurocognitive measures (p<0.05) compared to psychoeducation. Our findings suggest that SCIT is a feasible and promising intervention for the clinical symptoms and functioning of partially remitted patients with BD. Further longitudinal studies are needed to observe the long-term impact of SCIT on emotional and functional improvement in these patients. 10.1016/j.psychres.2019.03.002
    The relationship between cognitive and social functioning in older patients with bipolar disorder. Orhan Melis,Korten Nicole,Stek Max,Comijs Hannie,Schouws Sigfried,Dols Annemiek Journal of affective disorders OBJECTIVES:Patients with bipolar disorder (BD) show specific cognitive impairments, especially in the domains of attention, executive functioning and memory. Social and occupational problems seem to exist in 30-60% of BD patients. This study analysed the relationship between cognitive and social functioning in older age BD (OABD) patients. METHODS:This study included 63 OABD patients (aged > 60). Cognitive functioning was measured by an extensive neuropsychological assessment including global cognitive functioning, attention, learning and memory, executive functioning and verbal fluency. Social functioning, was obtained by clinical interview, including global social functioning, meaningful contacts and social participation. Linear regression analyses were conducted between cognitive performance and social functioning and the role of depression severity and disease duration was explored. RESULTS:Global social functioning, number of meaningful contacts and social participation were not interrelated. Global cognitive functioning, learning and memory and executive functioning were positively associated with global social functioning. No associations were found between cognitive functioning and social participation or meaningful contacts. Depression severity and disease duration were no effect modifiers. LIMITATIONS:Limitations include the use of a sample with relatively low cognitive and social impairments and the use of a cross-sectional research design. CONCLUSIONS:Global social functioning judged by the clinician was found to be independent of social functioning defined by the number of social contacts and social participation as reported by the patient. Global social functioning was related to cognitive functioning. An integrative treatment intervention including cognitive training and addressing social functioning may improve daily functioning in OABD patients. 10.1016/j.jad.2018.07.055