Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways.
Insomnia is the second most prevalent mental disorder, with no sufficient treatment available. Despite substantial heritability, insight into the associated genes and neurobiological pathways remains limited. Here, we use a large genetic association sample (n = 1,331,010) to detect novel loci and gain insight into the pathways, tissue and cell types involved in insomnia complaints. We identify 202 loci implicating 956 genes through positional, expression quantitative trait loci, and chromatin mapping. The meta-analysis explained 2.6% of the variance. We show gene set enrichments for the axonal part of neurons, cortical and subcortical tissues, and specific cell types, including striatal, hypothalamic, and claustrum neurons. We found considerable genetic correlations with psychiatric traits and sleep duration, and modest correlations with other sleep-related traits. Mendelian randomization identified the causal effects of insomnia on depression, diabetes, and cardiovascular disease, and the protective effects of educational attainment and intracranial volume. Our findings highlight key brain areas and cell types implicated in insomnia, and provide new treatment targets.
Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China.
Zhang Wen-Rui,Wang Kun,Yin Lu,Zhao Wen-Feng,Xue Qing,Peng Mao,Min Bao-Quan,Tian Qing,Leng Hai-Xia,Du Jia-Lin,Chang Hong,Yang Yuan,Li Wei,Shangguan Fang-Fang,Yan Tian-Yi,Dong Hui-Qing,Han Ying,Wang Yu-Ping,Cosci Fiammetta,Wang Hong-Xing
Psychotherapy and psychosomatics
OBJECTIVE:We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS:An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS:Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS:During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.
Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis.
Akingbuwa Wonuola A,Hammerschlag Anke R,Jami Eshim S,Allegrini Andrea G,Karhunen Ville,Sallis Hannah,Ask Helga,Askeland Ragna B,Baselmans Bart,Diemer Elizabeth,Hagenbeek Fiona A,Havdahl Alexandra,Hottenga Jouke-Jan,Mbarek Hamdi,Rivadeneira Fernando,Tesli Martin,van Beijsterveldt Catharina,Breen Gerome,Lewis Cathryn M,Thapar Anita,Boomsma Dorret I,Kuja-Halkola Ralf,Reichborn-Kjennerud Ted,Magnus Per,Rimfeld Kaili,Ystrom Eivind,Jarvelin Marjo-Riitta,Lichtenstein Paul,Lundstrom Sebastian,Munafò Marcus R,Plomin Robert,Tiemeier Henning,Nivard Michel G,Bartels Meike,Middeldorp Christel M,
Importance:Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective:To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants:This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures:Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures:Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results:The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008). Conclusions and Relevance:Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.
GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person.
Hu Youna,Shmygelska Alena,Tran David,Eriksson Nicholas,Tung Joyce Y,Hinds David A
Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10(-18); rs9479402 near VIP, P=3.9 × 10(-11); rs55694368 near PER2, P=2.6 × 10(-9); rs35833281 near HCRTR2, P=3.7 × 10(-9); rs11545787 near RASD1, P=1.4 × 10(-8); rs11121022 near PER3, P=2.0 × 10(-8); rs9565309 near FBXL3, P=3.5 × 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.
Brain mechanisms of insomnia: new perspectives on causes and consequences.
Van Someren Eus J W
While insomnia is the second most common mental disorder, progress in our understanding of underlying neurobiological mechanisms has been limited. The present review addresses the definition and prevalence of insomnia and explores its subjective and objective characteristics across the 24-hour day. Subsequently, the review extensively addresses how the vulnerability to develop insomnia is affected by genetic variants, early life stress, major life events, and brain structure and function. Further supported by the clear mental health risks conveyed by insomnia, the integrated findings suggest that the vulnerability to develop insomnia could rather be found in brain circuits regulating emotion and arousal than in circuits involved in circadian and homeostatic sleep regulation. Finally, a testable model is presented. The model proposes that in people with a vulnerability to develop insomnia, the locus coeruleus is more sensitive to-or receives more input from-the salience network and related circuits, even during rapid eye movement sleep, when it should normally be sound asleep. This vulnerability may ignite a downward spiral of insufficient overnight adaptation to distress, resulting in accumulating hyperarousal, which, in turn, impedes restful sleep and moreover increases the risk of other mental health adversity. Sensitized brain circuits are likely to be subjectively experienced as "sleeping with one eye open". The proposed model opens up the possibility for novel intervention studies and animal studies, thus accelerating the ignition of a neuroscience of insomnia, which is direly needed for better treatment.
Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.
McCall W Vaughn,Benca Ruth M,Rosenquist Peter B,Riley Mary Anne,McCloud Laryssa,Newman Jill C,Case Doug,Rumble Meredith,Krystal Andrew D
The American journal of psychiatry
OBJECTIVE:Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD:This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS:Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS:The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.
Efficacy of Digital Cognitive Behavioral Therapy for the Treatment of Insomnia Symptoms Among Pregnant Women: A Randomized Clinical Trial.
Importance:Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy. Objective:To test the efficacy of digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms. Design, Setting, and Participants:This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks' gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019. Interventions:Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy. Main Outcomes and Measures:All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up. Results:The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 [66.3%]), married or cohabiting (196 [94.2%]), had a college degree (180 [86.5%]), and earned $100 000 or more per year (141 [67.8%]). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = -0.36; 95% CI, -0.48 to -0.23; χ2 = 29.8; P < .001; d = -1.03). Improvements from baseline to postintervention for all secondary outcomes, with the exception of sleep duration, were statistically significant. A similar pattern of results was evident for the change from baseline to follow-up. Conclusions and Relevance:In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy. Trial Registration:ClinicalTrials.gov identifier: NCT02805998.
Sleep duration, cognitive decline, and dementia risk in older women.
Chen Jiu-Chiuan,Espeland Mark A,Brunner Robert L,Lovato Laura C,Wallace Robert B,Leng Xiaoyan,Phillips Lawrence S,Robinson Jennifer G,Kotchen Jane M,Johnson Karen C,Manson JoAnn E,Stefanick Marcia L,Sarto Gloria E,Mysiw W Jerry
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. METHODS:We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. RESULTS:We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. DISCUSSION:In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.
Maintenance treatment of insomnia: what can we learn from the depression literature?
Jindal Ripu D,Buysse Daniel J,Thase Michael E
The American journal of psychiatry
Insomnia and depression are common problems with profound public health consequences. When left untreated, both conditions have high rates of persistence and recurrence. Maintenance treatment for depression is fairly well established, but there is no evidence-based consensus regarding the safety and efficacy of maintenance therapy for insomnia. Consequently, long-term treatment of insomnia is driven primarily by the individual choices of patients and their clinicians. This article compares and contrasts the current state of research in the maintenance therapy of depression and insomnia and highlights gaps in the insomnia literature.
Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: Sleep and psychological effects.
Savard Josée,Simard Sébastien,Ivers Hans,Morin Charles M
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:Chronic insomnia is highly prevalent in cancer patients. Cognitive-behavioral therapy (CBT) is considered the treatment of choice for chronic primary insomnia. However, no randomized controlled study has been conducted on its efficacy for insomnia secondary to cancer. Using a randomized controlled design, this study conducted among breast cancer survivors evaluated the effect of CBT on sleep, assessed both subjectively and objectively, and on hypnotic medication use, psychological distress, and quality of life. PATIENTS AND METHODS:Fifty-seven women with insomnia caused or aggravated by breast cancer were randomly assigned to CBT (n = 27) or a waiting-list control condition (n = 30). The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue management. Follow-up evaluations were carried out 3, 6, and 12 months after the treatment. RESULTS:Participants who received the insomnia treatment had significantly better subjective sleep indices (daily sleep diary, Insomnia Severity Index), a lower frequency of medicated nights, lower levels of depression and anxiety, and greater global quality of life at post-treatment compared with participants of the control group after their waiting period. Results were more equivocal on polysomnographic indices. Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinically significant. CONCLUSION:This study supports the efficacy of CBT for insomnia secondary to breast cancer.
Mindfulness-based cognitive therapy improves polysomnographic and subjective sleep profiles in antidepressant users with sleep complaints.
Britton Willoughby B,Haynes Patricia L,Fridel Keith W,Bootzin Richard R
Psychotherapy and psychosomatics
BACKGROUND:Many antidepressant medications (ADM) are associated with disruptions in sleep continuity that can compromise medication adherence and impede successful treatment. The present study investigated whether mindfulness meditation (MM) training could improve self-reported and objectively measured polysomnographic (PSG) sleep profiles in depressed individuals who had achieved at least partial remission with ADM, but still had residual sleep complaints. METHODS:Twenty-three ADM users with sleep complaints were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep, residual depression symptoms. RESULTS:Compared to controls, the MBCT participants improved on both PSG and subjective measures of sleep. They showed a pattern of decreased wake time and increased sleep efficiency. Sleep depth, as measured by stage 1 and slow-wave sleep, did not change as a result of mindfulness training. CONCLUSIONS:MM is associated with increases in both objectively and subjectively measured sleep continuity in ADM users. MM training may serve as more desirable and cost-effective alternative to discontinuation or supplementation with hypnotics, and may contribute to a more sustainable recovery from depression.
Sleep disturbance in bipolar disorder: therapeutic implications.
Plante David T,Winkelman John W
The American journal of psychiatry
In this review, the authors detail our current understanding of the crucial role that sleep and its disturbances play in bipolar disorder. Multiple lines of evidence suggest that impaired sleep can induce and predict manic episodes. Similarly, treatment of sleep disturbance may serve as both a target of treatment and a measure of response in mania. The depressive phase of bipolar illness is marked by sleep disturbance that may be amenable to somatic therapies that target sleep and circadian rhythms. Residual insomnia in the euthymic period may represent a vulnerability to affective relapse in susceptible patients. Given the importance of sleep in all phases of bipolar disorder, appropriate evaluation and management of sleep disturbance in patients with bipolar illness is further detailed.
Insomnia with objective short sleep duration is associated with type 2 diabetes: A population-based study.
Vgontzas Alexandros N,Liao Duanping,Pejovic Slobodanka,Calhoun Susan,Karataraki Maria,Bixler Edward O
OBJECTIVE:We examined the joint effects of insomnia and objective short sleep duration, the combination of which is associated with higher morbidity, on diabetes risk. RESEARCH DESIGN AND METHODS:A total of 1,741 men and women randomly selected from Central Pennsylvania were studied in the sleep laboratory. Insomnia was defined by a complaint of insomnia with duration of >or=1 year, whereas poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, or early final awakening. Polysomnographic sleep duration was classified into three categories: >or=6 h of sleep (top 50% of the sample); 5-6 h (approximately third quartile of the sample); and <or=5 h (approximately the bottom quartile of the sample). Diabetes was defined either based on a fasting blood glucose >126 mg/dl or use of medication. In the logistic regression model, we simultaneously adjusted for age, race, sex, BMI, smoking, alcohol use, depression, sleep-disordered breathing, and periodic limb movement. RESULTS:Chronic insomnia but not poor sleep was associated with a higher risk for diabetes. Compared with the normal sleeping and >or=6 h sleep duration group, the highest risk of diabetes was in individuals with insomnia and <or=5 h sleep duration group (odds ratio [95% CI] 2.95 [1.2-7.0]) and in insomniacs who slept 5-6 h (2.07 [0.68-6.4]). CONCLUSIONS:Insomnia with short sleep duration is associated with increased odds of diabetes. Objective sleep duration may predict cardiometabolic morbidity of chronic insomnia, the medical impact of which has been underestimated.
Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial.
Black David S,O'Reilly Gillian A,Olmstead Richard,Breen Elizabeth C,Irwin Michael R
JAMA internal medicine
IMPORTANCE:Sleep disturbances are most prevalent among older adults and often go untreated. Treatment options for sleep disturbances remain limited, and there is a need for community-accessible programs that can improve sleep. OBJECTIVE:To determine the efficacy of a mind-body medicine intervention, called mindfulness meditation, to promote sleep quality in older adults with moderate sleep disturbances. DESIGN, SETTING, AND PARTICIPANTS:Randomized clinical trial with 2 parallel groups conducted from January 1 to December 31, 2012, at a medical research center among an older adult sample (mean [SD] age, 66.3 [7.4] years) with moderate sleep disturbances (Pittsburgh Sleep Quality Index [PSQI] >5). INTERVENTIONS:A standardized mindful awareness practices (MAPs) intervention (n = 24) or a sleep hygiene education (SHE) intervention (n = 25) was randomized to participants, who received a 6-week intervention (2 hours per week) with assigned homework. MAIN OUTCOMES AND MEASURES:The study was powered to detect between-group differences in moderate sleep disturbance measured via the PSQI at postintervention. Secondary outcomes pertained to sleep-related daytime impairment and included validated measures of insomnia symptoms, depression, anxiety, stress, and fatigue, as well as inflammatory signaling via nuclear factor (NF)-κB. RESULTS:Using an intent-to-treat analysis, participants in the MAPs group showed significant improvement relative to those in the SHE group on the PSQI. With the MAPs intervention, the mean (SD) PSQIs were 10.2 (1.7) at baseline and 7.4 (1.9) at postintervention. With the SHE intervention, the mean (SD) PSQIs were 10.2 (1.8) at baseline and 9.1 (2.0) at postintervention. The between-group mean difference was 1.8 (95% CI, 0.6-2.9), with an effect size of 0.89. The MAPs group showed significant improvement relative to the SHE group on secondary health outcomes of insomnia symptoms, depression symptoms, fatigue interference, and fatigue severity (P < .05 for all). Between-group differences were not observed for anxiety, stress, or NF-κB, although NF-κB concentrations significantly declined over time in both groups (P < .05). CONCLUSIONS AND RELEVANCE:The use of a community-accessible MAPs intervention resulted in improvements in sleep quality at immediate postintervention, which was superior to a highly structured SHE intervention. Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01534338.
Melatonin and its analogs in insomnia and depression.
Cardinali Daniel P,Srinivasan Venkataramanujan,Brzezinski Amnon,Brown Gregory M
Journal of pineal research
Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.
Nature reviews. Disease primers
Insomnia disorder affects a large proportion of the population on a situational, recurrent or chronic basis and is among the most common complaints in medical practice. The disorder is predominantly characterized by dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep, along with substantial distress and impairments of daytime functioning. It can present as the chief complaint or, more often, co-occurs with other medical or psychiatric disorders, such as pain and depression. Persistent insomnia has been linked with adverse long-term health outcomes, including diminished quality of life and physical and psychological morbidity. Despite its high prevalence and burden, the aetiology and pathophysiology of insomnia is poorly understood. In the past decade, important changes in classification and diagnostic paradigms have instigated a move from a purely symptom-based conceptualization to the recognition of insomnia as a disorder in its own right. These changes have been paralleled by key advances in therapy, with generic pharmacological and psychological interventions being increasingly replaced by approaches that have sleep-specific and insomnia-specific therapeutic targets. Psychological and pharmacological therapies effectively reduce the time it takes to fall asleep and the time spent awake after sleep onset, and produce a modest increase in total sleep time; these are outcomes that correlate with improvements in daytime functioning. Despite this progress, several challenges remain, including the need to improve our knowledge of the mechanisms that underlie insomnia and to develop more cost-effective, efficient and accessible therapies.
Biological and clinical insights from genetics of insomnia symptoms.
Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.
Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial.
McCall William V,Benca Ruth M,Rosenquist Peter B,Youssef Nagy A,McCloud Laryssa,Newman Jill C,Case Doug,Rumble Meredith E,Szabo Steven T,Phillips Marjorie,Krystal Andrew D
The American journal of psychiatry
OBJECTIVE:The authors sought to determine whether targeted treatment of insomnia with controlled-release zolpidem (zolpidem-CR) in suicidal adults with insomnia would provide a reduction in suicidal ideation superior to placebo. METHODS:Reducing Suicidal Ideation Through Insomnia Treatment was an 8-week three-site double-blind placebo-controlled parallel-group randomized controlled trial of zolpidem-CR hypnotic therapy compared with placebo, in conjunction with an open-label selective serotonin reuptake inhibitor. Participants were medication-free 18- to 65-year-olds with major depressive disorder, insomnia, and suicidal ideation. Suicidal ideation was the main outcome, measured first by the Scale for Suicide Ideation and second by the Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS:A total of 103 participants were randomly assigned to receive zolpidem-CR (N=51) or placebo (N=52) (64 women and 39 men; mean age=40.5 years). Zolpidem-CR had a robust anti-insomnia effect, especially in patients with the most severe insomnia symptoms. No significant treatment effect was observed on the Scale for Suicide Ideation (least squares mean estimate=-0.56, SE=0.83, 95% CI=-2.19, 1.08), but the reduction in scores was significantly positively related to improvement in insomnia after accounting for the effect of other depression symptoms. The C-SSRS indicated that zolpidem-CR had a significant treatment effect (least squares mean estimate=-0.26, SE=0.12, 95% CI=-0.50, -0.02). The advantage for zolpidem-CR in reducing suicidal ideation on the C-SSRS was greater in patients with more severe insomnia. No deaths or suicide attempts occurred. CONCLUSIONS:Although the results do not support the routine prescription of hypnotic medication for mitigating suicidal ideation in all depressed outpatients with insomnia, they suggest that coprescription of a hypnotic during initiation of an antidepressant may be beneficial in suicidal outpatients, especially in patients with severe insomnia.
Insomnia disorder subtypes derived from life history and traits of affect and personality.
Blanken Tessa F,Benjamins Jeroen S,Borsboom Denny,Vermunt Jeroen K,Paquola Casey,Ramautar Jennifer,Dekker Kim,Stoffers Diederick,Wassing Rick,Wei Yishul,Van Someren Eus J W
The lancet. Psychiatry
BACKGROUND:Insomnia disorder is the second most prevalent mental disorder, and it is a primary risk factor for depression. Inconsistent clinical and biomarker findings in patients with insomnia disorder suggest that heterogeneity exists and that subtypes of this disease remain unrecognised. Previous top-down proposed subtypes in nosologies have had insufficient validity. In this large-scale study, we aimed to reveal robust subtypes of insomnia disorder by use of data-driven analyses on a multidimensional set of biologically based traits. METHODS:In this series of studies, we recruited participants from the Netherlands Sleep Registry, a database of volunteers aged 18 years or older, who we followed up online to survey traits, sleep, life events, and health history with 34 selected questionnaires of which participants completed at least one. We identified insomnia disorder subtypes by use of latent class analyses. We evaluated the value of our identified subtypes of insomnia disorder by use of a second, non-overlapping cohort who were recruited through a newsletter that was emailed to a new sample of Netherlands Sleep Registry participants, and by assessment of within-subject stability over several years of follow-up. We extensively tested the clinical validity of these subtypes for the development of sleep complaints, comorbidities (including depression), and response to benzodiazepines; in two subtypes of insomnia disorder, we also assessed the clinical relevance of these subtypes by use of an electroencephalogram biomarker and the effectiveness of cognitive behavioural therapy. To facilitate implementation, we subsequently constructed a concise subtype questionnaire and we validated this questionnaire in the second, non-overlapping cohort. FINDINGS:4322 Netherlands Sleep Registry participants completed at least one of the selected questionnaires, a demographic questionnaire, and an assessment of their Insomnia Severity Index (ISI) between March 2, 2010, and Oct 28, 2016. 2224 (51%) participants had probable insomnia disorder, defined as an ISI score of at least 10, and 2098 (49%) participants with a lower ISI score served as a control group. With a latent class analysis of the questionnaire responses of 2224 participants, we identified five novel insomnia disorder subtypes: highly distressed, moderately distressed but reward sensitive (ie, with intact responses to pleasurable emotions), moderately distressed and reward insensitive, slightly distressed with high reactivity (to their environment and life events), and slightly distressed with low reactivity. In a second, non-overlapping replication sample of 251 new participants who were assessed between June 12, 2017, and Nov 26, 2017, five subtypes were also identified to be optimal. In both the development sample and replication sample, each participant was classified as having only one subtype with high posterior probability (0·91-1·00). In 215 of the original sample of 2224 participants with insomnia who were reassessed 4·8 (SD 1·6) years later (between April 13, 2017, and June 21, 2017), the probability of maintaining their original subtype was 0·87, indicating a high stability of the classification. We found differences between the identified subtypes in developmental trajectories, response to treatment, the presence of an electroencephalogram biomarker, and the risk of depression that was up to five times different between groups, which indicated a clinical relevance of these subtypes. INTERPRETATION:High-dimensional data-driven subtyping of people with insomnia has addressed an unmet need to reduce the heterogeneity of insomnia disorder. Subtyping facilitates identification of the underlying causes of insomnia, development of personalised treatments, and selection of patients with the highest risk of depression for inclusion in trials regarding prevention of depression. FUNDING:European Research Council and Netherlands Organization for Scientific Research.
Effectiveness of an online insomnia program (SHUTi) for prevention of depressive episodes (the GoodNight Study): a randomised controlled trial.
Christensen Helen,Batterham Philip J,Gosling John A,Ritterband Lee M,Griffiths Kathleen M,Thorndike Frances P,Glozier Nick,O'Dea Bridianne,Hickie Ian B,Mackinnon Andrew J
The lancet. Psychiatry
BACKGROUND:In view of the high co-occurrence of depression and insomnia, a novel way to reduce the risk of escalating depression might be to offer an insomnia intervention. We aimed to assess whether an online self-help insomnia program could reduce depression symptoms. METHODS:We did this randomised controlled trial at the Australian National University in Canberra, Australia. Internet users (aged 18-64 years) with insomnia and depression symptoms, but who did not meet criteria for major depressive disorder, were randomly assigned (1:1), via computer-generated randomisation, to receive SHUTi, a 6 week, modular, online insomnia program based on cognitive behavioural therapy for insomnia, or HealthWatch, an interactive, attention-matched, internet-based placebo control program. Randomisation was stratified by age and sex. Telephone-based interviewers, statisticians, and chief investigators were masked to group allocation. The primary outcome was depression symptoms at 6 months, as measured with the Patient Health Questionnaire (PHQ-9). The primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000121965. FINDINGS:Between April 30, 2013, and June 9, 2014, we randomly assigned 1149 participants to receive SHUTi (n=574) or HealthWatch (n=575), of whom 581 (51%) participants completed the study program assessments at 6 weeks and 504 (44%) participants completed 6 months' follow-up. SHUTi significantly lowered depression symptoms on the PHQ-9 at 6 weeks and 6 months compared with HealthWatch (F[degrees of freedom 2,640·1]=37·2, p<0·0001). Major depressive disorder was diagnosed in 22 (4%) participants at 6 months (n=9 in the SHUTi group and n=13 in the HealthWatch group), with no superior effect of SHUTi versus HealthWatch (Fisher's exact test=0·52; p=0·32). No adverse events were reported. INTERPRETATION:Online cognitive behaviour therapy for insomnia treatment is a practical and effective way to reduce depression symptoms and could be capable of reducing depression at the population level by use of a fully automatised system with the potential for wide dissemination. FUNDING:Australian National Health and Medical Research Council.
Genome-wide analysis of insomnia disorder.
Stein Murray B,McCarthy Michael J,Chen Chia-Yen,Jain Sonia,Gelernter Joel,He Feng,Heeringa Steven G,Kessler Ronald C,Nock Matthew K,Ripke Stephan,Sun Xiaoying,Wynn Gary H,Smoller Jordan W,Ursano Robert J
Insomnia is a worldwide problem with substantial deleterious health effects. Twin studies have shown a heritable basis for various sleep-related traits, including insomnia, but robust genetic risk variants have just recently begun to be identified. We conducted genome-wide association studies (GWAS) of soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). GWAS were carried out separately for each ancestral group (EUR, AFR, LAT) using logistic regression for each of the STARRS component studies (including 3,237 cases and 14,414 controls), and then meta-analysis was conducted across studies and ancestral groups. Heritability (SNP-based) for lifetime insomnia disorder was significant (h = 0.115, p = 1.78 × 10 in EUR). A meta-analysis including three ancestral groups and three study cohorts revealed a genome-wide significant locus on Chr 7 (q11.22) (top SNP rs186736700, OR = 0.607, p = 4.88 × 10) and a genome-wide significant gene-based association (p = 7.61 × 10) in EUR for RFX3 on Chr 9. Polygenic risk for sleeplessness/insomnia severity in UK Biobank was significantly positively associated with likelihood of insomnia disorder in STARRS. Genetic contributions to insomnia disorder in STARRS were significantly positively correlated with major depressive disorder (r = 0.44, se = 0.22, p = 0.047) and type 2 diabetes (r = 0.43, se = 0.20, p = 0.037), and negatively with morningness chronotype (r = -0.34, se = 0.17, p = 0.039) and subjective well being (r = -0.59, se = 0.23, p = 0.009) in external datasets. Insomnia associated loci may contribute to the genetic risk underlying a range of health conditions including psychiatric disorders and metabolic disease.
Prevalence and correlates of non-suicidal self-injury among lesbian, gay, bisexual, and transgender individuals: A systematic review and meta-analysis.
Liu Richard T,Sheehan Ana E,Walsh Rachel F L,Sanzari Christina M,Cheek Shayna M,Hernandez Evelyn M
Clinical psychology review
The current review presents a meta-analysis of the existing empirical literature on the prevalence of non-suicidal self-injury (NSSI) among lesbian, gay, bisexual, and transgender (LGBT) individuals, as well as on correlates of NSSI within sexual and gender minority populations. Eligible publications (n = 51) were identified through a systematic search of PsycINFO, MEDLINE, and Embase, supplemented by a search of references of prior reviews on this topic. NSSI prevalence rates were quite elevated among sexual (29.68% lifetime) and gender (46.65% lifetime) minority individuals compared to heterosexual and/or cisgender peers (14.57% lifetime), with transgender (46.65% lifetime) and bisexual (41.47% lifetime) individuals being at greatest risk. Even among these group findings, sexual minority youth emerged as an especially vulnerable population. Moreover, current evidence suggests these rates and differences between LGBT and heterosexual and/or cisgender peers have not declined over time. These findings may in some measure be due to the existence of LGBT-specific risk correlates combined with general risk correlates being more severe among sexual and gender minority populations. Additional research, particularly employing a longitudinal design, is needed in this area to advance efforts to reduce risk for NSSI among sexual and gender minority individuals.
An examination of the relationship between shame, guilt and self-harm: A systematic review and meta-analysis.
Sheehy Kate,Noureen Amna,Khaliq Ayesha,Dhingra Katie,Husain Nusrat,Pontin Eleanor E,Cawley Rosanne,Taylor Peter J
Clinical psychology review
Self-harm is a major public health concern associated with suicide risk and significant psychological distress. Theories suggest that aversive emotional states are an important process that drives self-harm. Shame and guilt may, in particular, be important emotions in self-harm. This review therefore sought to provide a systematic review and meta-analysis of the relationship between shame, guilt, and self-harm. A systematic search of electronic databases (PsycINFO; Medline; CINAHL Plus; Web of Science and ProQuest) was undertaken to identify studies measuring shame, guilt and self-harm (including suicidal and non-suicidal behaviour). Meta-analysis was undertaken where papers focused on the same subtype of shame or guilt and shared a common outcome. Thirty studies were identified for inclusion. Most forms of shame were associated with non-suicidal self-injury (NSSI), but research was sparse concerning suicidal behaviour. Fewer studies examined guilt and findings were more varied. Methodological issues included a paucity of longitudinal designs and lack of justification for sample sizes. Results of this review support the link between shame and self-harm, particularly NSSI. The direction of this relationship is yet to be established. Clinically, consideration should be given to the role of shame amongst individuals who present with NSSI. This review was pre-registered on PROSPERO (CRD42017056165).
Attempted suicide v. non-suicidal self-injury: behaviour, syndrome or diagnosis?
Butler Aine M,Malone Kevin
The British journal of psychiatry : the journal of mental science
Nomenclature used to describe acts of self-harm without fatal consequences varies considerably. The term 'non-suicidal self-injury' (NSSI) offers an opportunity to clarify study in this field, dichotomising the presence or absence of suicidal intent. This may improve consistency in reporting suicide and self-injurious behaviour with implications for management and prognosis.
Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.
Reitz Sarah,Kluetsch Rosemarie,Niedtfeld Inga,Knorz Teresa,Lis Stefanie,Paret Christian,Kirsch Peter,Meyer-Lindenberg Andreas,Treede Rolf-Detlef,Baumgärtner Ulf,Bohus Martin,Schmahl Christian
The British journal of psychiatry : the journal of mental science
BACKGROUND:Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. AIMS:Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. METHOD:In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. RESULTS:We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. CONCLUSIONS:Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension.
Sporadic and recurrent non-suicidal self-injury before age 14 and incident onset of psychiatric disorders by 17 years: prospective cohort study.
Wilkinson Paul O,Qiu Tianyou,Neufeld Sharon,Jones Peter B,Goodyer Ian M
The British journal of psychiatry : the journal of mental science
BACKGROUND:Non-suicidal self-injury (NSSI) is highly prevalent in adolescents and may be a behavioural marker for emergent mental illnesses. Aims To determine whether sporadic or recurrent NSSI up to the age of 14 years predicted increased risk of new onset of psychiatric disorder in the subsequent 3 years, independent of psychiatric symptoms and social risk factors. METHOD:In total, 945 individuals aged 14 years with no past/present history of mental illness completed a clinical interview and completed a questionnaire about NSSI at the ages of 14 and 17 years. RESULTS:Recurrent NSSI at baseline predicted total disorders, depression and eating disorders. Sporadic baseline NSSI predicted new onset of anxiety disorders only. CONCLUSIONS:NSSI (especially recurrent NSSI) in the early-adolescent years is a behavioural marker of newly emerging mental illnesses. Professionals should treat both recurrent and sporadic NSSI as important risk factors, and prevention strategies could be targeted at this vulnerable group. Declaration of interest None.
Non-suicidal self-injury v. attempted suicide: new diagnosis or false dichotomy?
Kapur Navneet,Cooper Jayne,O'Connor Rory C,Hawton Keith
The British journal of psychiatry : the journal of mental science
Non-suicidal self-injury (NSSI) is a term that is becoming popular especially in North America and it has been proposed as a new diagnosis in DSM-5. In this paper we consider what self-harm research can tell us about the concept of NSSI and examine the potential pitfalls of introducing NSSI into clinical practice.
Associations of adverse childhood experiences and social support with self-injurious behaviour and suicidality in adolescents.
Wan Yuhui,Chen Ruoling,Ma Shuangshuang,McFeeters Danielle,Sun Ying,Hao Jiahu,Tao Fangbiao
The British journal of psychiatry : the journal of mental science
BACKGROUND:There is little investigation on the interaction effects of adverse childhood experiences (ACEs) and social support on non-suicidal self-injury (NSSI), suicidal ideation and suicide attempt in community adolescent populations, or gender differences in these effects.AimsTo examine the individual and interaction effects of ACEs and social support on NSSI, suicidal ideation and suicide attempt in adolescents, and explore gender differences. METHOD:A school-based health survey was conducted in three provinces in China between 2013-2014. A total of 14 820 students aged 10-20 years completed standard questionnaires, to record details of ACEs, social support, NSSI, suicidal ideation and suicide attempt. RESULTS:Of included participants, 89.4% reported one or more category of ACEs. The 12-month prevalence of NSSI, suicidal ideation and suicide attempt was 26.1%, 17.5% and 4.4%, respectively; all were significantly associated with increased ACEs and lower social support. The multiple adjusted odds ratio of NSSI in low versus high social support was 2.27 (95% CI 1.85-2.67) for girls and 1.81 (95% CI 1.53-2.14) for boys, and their ratio (Ratio of two odds ratios, ROR) was 1.25 (P = 0.037). Girls with high ACEs scores (5-6) and moderate or low social support also had a higher risk of suicide attempt than boys (RORs: 2.34, 1.84 and 2.02, respectively; all P < 0.05). CONCLUSIONS:ACEs and low social support are associated with increased risk of NSSI and suicidality in Chinese adolescents. Strategies to improve social support, particularly among female adolescents with a high number of ACEs, should be an integral component of targeted mental health interventions.Declaration of interestNone.
A systematic review of daily life studies on non-suicidal self-injury based on the four-function model.
Hepp Johanna,Carpenter Ryan W,Störkel Lisa M,Schmitz Sara E,Schmahl Christian,Niedtfeld Inga
Clinical psychology review
Non-suicidal self-injury (NSSI) is a prevalent, impairing, and trans-diagnostic behavior that can be comprehensively assessed in daily life studies. We conducted a systematic literature review of 35 Ambulatory Assessment and Daily Diary studies of NSSI, to achieve three aims. First, we reviewed descriptive evidence on NSSI acts. On average, studies observed 1.6 acts per participant, but evidence regarding methods, pain, and context was sparse. Second, we reviewed evidence on NSSI urges. On average, studies reported 4.3 urges per participant. Urges were also associated with increased negative affect and predicted later acts. Third, we reviewed evidence on the Four-function Model of NSSI. Eight studies partially supported negative intrapersonal reinforcement, showing increased negative affect pre NSSI, but, of these, only four studies supported decreased negative affect post NSSI. Additionally, only three studies supported positive intrapersonal reinforcement, showing decreased positive affect pre and increased positive affect post NSSI. Evidence for the interpersonal functions was limited to two studies and inconclusive. We recommend assessing the intensity, frequency, and context of acts and urges, as well as pain and urge duration in future studies. We also recommend follow-up prompts after acts and urges to better track affect trajectories, and a detailed assessment of interpersonal events.
Conceptualizing the neurobiology of non-suicidal self-injury from the perspective of the Research Domain Criteria Project.
Westlund Schreiner Melinda,Klimes-Dougan Bonnie,Begnel Erin D,Cullen Kathryn R
Neuroscience and biobehavioral reviews
Non-suicidal self-injury (NSSI) commonly starts in adolescence and is associated with an array of negative outcomes. Neurobiological research investigating NSSI is in its early stages and most studies have examined this behavior within the context of specific diagnoses. However, the Research Domain Criteria (RDoC) initiative encourages researchers to examine brain-behavior relationships across diagnoses. This review on the neurobiology associated with NSSI is organized using the domains proposed by RDoC: Negative Valence, Positive Valence, Cognitive, Social Processes, and Arousal/Regulatory Systems. Evidence of neurobiological anomalies is found in each of these domains. We also propose future research directions, especially in regard to human development. Future NSSI studies should address this behavior independent of diagnosis, examine relevant constructs across multiple units of analysis, and assess how systems change across development and course of illness. These advances will be essential for guiding neurobiologically informed intervention and prevention strategies to target NSSI. In doing so, we may prevent the associated negative outcomes across the lifespan.
[Non-suicidal self-injury and comorbid mental disorders: a review].
Nitkowski D,Petermann F
Fortschritte der Neurologie-Psychiatrie
BACKGROUND:Non-suicidal self-injury (NSSI) is described as deliberate destruction of one's body without suicidal intent. It is a fact that the phenomenon is associated with several mental disorders. Even so, a systematic review is lacking. The aim of this article is to compile which psychiatric disorders occur most frequently with NSSI. METHODS:From a literature search, 21 of 1298 studies fulfilled the inclusion criteria. RESULTS:Mood disorders, especially a recurrent major depression disorder, and personality disorders, particularly the borderline syndrome, are closely connected with NSSI in adolescence and adulthood. Self-injury is also present in anxiety and substance use disorders. In adolescence, externalising disorders are related to NSSI, too. CONCLUSIONS:Depressive disorders and the borderline personality disorders are robustly associated with NSSI. It is still unknown whether or not the occurrence of NSSI with particular disorders can be explained by comorbidity with the borderline syndrome.
Correlates of suicide attempts among self-injurers: a meta-analysis.
Victor Sarah E,Klonsky E David
Clinical psychology review
Suicide attempts (SAs) are common among those who engage in non-suicidal self-injury (NSSI). It is therefore important to determine which suicide risk factors are most predictive of SA among those who self-injure. Toward this aim, we conducted a systematic review of studies examining predictors of SA history among self-injurers. A total of 52 empirical articles provided data comparing self-injurers with and without SA. From these studies we focused our meta-analysis on the 20 variables that were evaluated with respect to SA history in five or more different samples. The strongest correlate of SA history was suicidal ideation. After suicidal ideation, the strongest predictors of SA history were NSSI frequency, number of NSSI methods, and hopelessness. Additional, moderate predictors of SA history included Borderline Personality Disorder, impulsivity, Post-Traumatic Stress Disorder, the NSSI method of cutting, and depression. Demographic characteristics, such as gender, ethnicity, and age, were weakly associated with SA history. Notably, some oft-cited risk factors for SA displayed small or negligible associations with SA among self-injurers, including histories of sexual and physical abuse, anxiety, substance use, and eating disorders. Findings have implications for conceptual models of the NSSI-SA relationship and the evaluation of suicide risk among self-injuring populations.
Is psychotherapy effective for reducing suicide attempt and non-suicidal self-injury rates? Meta-analysis and meta-regression of literature data.
Calati Raffaella,Courtet Philippe
Journal of psychiatric research
OBJECTIVE:To determine the efficacy of psychotherapy interventions for reducing suicidal attempts (SA) and non-suicidal self-injury (NSSI). METHODS:Meta-analysis of randomized controlled trials (RCTs) comparing psychotherapy interventions and treatment as usual (TAU; including also enhanced usual care, psychotropic treatment alone, cognitive remediation, short-term problem-oriented approach, supportive relationship treatment, community treatment by non-behavioral psychotherapy experts, emergency care enhanced by provider education, no treatment) for SA/NSSI. RCTs were extracted from MEDLINE, EMBASE, PsycINFO and Cochrane Library and analyzed using the Cochrane Collaboration Review Manager Software and Comprehensive Meta-analysis. RESULTS:In the 32 included RCTs, 4114 patients were randomly assigned to receive psychotherapy (n = 2106) or TAU (n = 2008). Patients who received psychotherapy were less likely to attempt suicide during the follow-up. The pooled risk difference for SA was -0.08 (95% confidence intervals = -0.04 to -0.11). The absolute risk reduction was 6.59% (psychotherapy: 9.12%; TAU: 15.71%), yielding an estimated number needed to treat of 15. Sensitivity analyses showed that psychotherapy was effective for SA mainly in adults, outpatients, patients with borderline personality disorder, previously and non-previously suicidal patients (heterogeneous variable that included past history of SA, NSSI, deliberate self-harm, imminent suicidal risk or suicidal ideation), long- and short-term therapies, TAU only as a control condition, and mentalization-based treatment (MBT). No evidence of efficacy was found for NSSI, with the exception of MBT. Between-study heterogeneity and publication bias were detected. In the presence of publication bias, the Duval and Tweedie's "trim and fill" method was applied. CONCLUSION:Psychotherapy seems to be effective for SA treatment. However, trials with lower risk of bias, more homogeneous outcome measures and longer follow-up are needed.
A behavioral and cognitive neuroscience perspective on impulsivity, suicide, and non-suicidal self-injury: Meta-analysis and recommendations for future research.
Liu Richard T,Trout Zoë M,Hernandez Evelyn M,Cheek Shayna M,Gerlus Nimesha
Neuroscience and biobehavioral reviews
We conducted a meta-analysis of neurobehavioral and neurocognitive indices of impulsivity in relation to suicidal thoughts and behaviors, as well as non-suicidal self-injury (NSSI). In our systematic review, 34 studies were identified and submitted to a random-effects meta-analysis. A small pooled effect size was observed for the association between behavioral impulsivity and NSSI (OR=1.34, p<0.05). A small-to-medium pooled effect size (OR=2.23, p<0.001) was found for the association between behavioral impulsivity and suicide attempts, and a medium-to-large pooled effect size was observed for this outcome in relation to cognitive impulsivity (OR=3.14, p<0.01). Length of time between suicide attempt and impulsivity assessment moderated the strength of the relation between impulsivity and attempts, with a large pooled effect size (OR=5.54, p<0.001) evident when the suicide attempt occurred within a month of behavioral impulsivity assessment. Studies of clinically significant NSSI temporally proximal to impulsivity assessment are needed. Longitudinal research is required to clarify the prognostic value of behavioral and cognitive impulsivity for short-term risk for self-harm.
A meta-analysis of the prevalence of different functions of non-suicidal self-injury.
Taylor Peter J,Jomar Khowla,Dhingra Katie,Forrester Rebecca,Shahmalak Ujala,Dickson Joanne M
Journal of affective disorders
BACKGROUND:A broad variety of different functions can underlie acts of Non-suicidal self-injury (NSSI). Whilst research so far has identified many of the commonly reported functions, no reliable estimates of prevalence currently exist for these different NSSI functions. Understanding the prevalence of NSSI functions represents a key to better understanding the phenomenology of NSSI and addressing the differing needs of the NSSI population. We conducted a systematic review and meta-analysis of the prevalence of NSSI functions in community and clinical samples. METHOD:A literature search of electronic databases PsycINFO, Medline, and Web of Science from date of inception to March 2017 was undertaken. A pre-specified framework for categorising different functions of NSSI was used to collate data from across studies. A random-effects meta-analysis of prevalence was then undertaken on these data. RESULTS:Intrapersonal functions (66-81%), and especially those concerning emotion regulation were most commonly reported by individuals who engage in NSSI (63-78%). Interpersonal functions (e.g., expressing distress) were less common (33-56%). LIMITATIONS:The review was limited to English-language articles. Reviewed articles were inconsistent in their measurement of NSSI. Inconsistency within pooled prevalence estimates was high when moderators were not accounted for. CONCLUSIONS:Findings indicate that intrapersonal functions of NSSI are most common and are present for the majority of participants. This finding supports dominant emotion-regulation models of NSSI, and the use of interventions that work to improve emotion-regulation ability. However, interpersonal functions remain endorsed by a substantial portion of participants.
Emotion dysregulation and non-suicidal self-injury: A systematic review and meta-analysis.
Wolff Jennifer C,Thompson Elizabeth,Thomas Sarah A,Nesi Jacqueline,Bettis Alexandra H,Ransford Briana,Scopelliti Katie,Frazier Elisabeth A,Liu Richard T
European psychiatry : the journal of the Association of European Psychiatrists
BACKGROUND:Over the past several years there has been considerable interest in the relation between emotion dysregulation and non-suicidal self-injury (NSSI), particularly given that rates of NSSI have been increasing and NSSI is a critical risk factor for suicidal behavior. To date, however, no synthesis of empirical findings exists. METHODS:The present study presents a comprehensive meta-analytic review of the literature on the association between NSSI and emotion dysregulation. A total of 48 publications, including 49 independent samples, were included in this analysis. RESULTS:Overall, a significant association was found between emotion dysregulation and NSSI (pooled OR = 3.03 [95% CI = 2.56-3.59]). This association was reduced but remained significant (OR = 2.40 [95% CI = 2.01-2.86]) after adjustment for publication bias. Emotion dysregulation subscales most strongly associated with NSSI included limited access to regulation strategies, non-acceptance of emotional responses, impulse control difficulties, and difficulties engaging goal-directed behavior. Lack of emotional awareness/clarity and cognitive aspects of dysregulation yielded weaker, yet significant, positive associations with NSSI. CONCLUSIONS:Findings support the notion that greater emotion dysregulation is associated with higher risk for NSSI among individuals across settings, regardless of age or sex. Furthermore, findings reveal facets of dysregulation that may have unique implications for NSSI. This meta-analysis highlights the importance of better understanding emotion dysregulation as a treatment target for preventing NSSI.
The impact of affective information on working memory: A pair of meta-analytic reviews of behavioral and neuroimaging evidence.
Schweizer Susanne,Satpute Ajay B,Atzil Shir,Field Andy P,Hitchcock Caitlin,Black Melissa,Barrett Lisa Feldman,Dalgleish Tim
Everyday life is defined by goal states that are continuously reprioritized based on available, often affective information. To pursue these goals, individuals need to process and maintain goal-relevant information, while ignoring potentially salient information that distracts resources from these goals. Empirically, this ability has typically been operationalized as working memory (WM) capacity. A growing body of research is investigating the impact of information's affective salience on WM capacity. In the present review we address this question by exploring the potential differential impact of affective compared with neutral information on WM, and the underlying neural substrates. One-hundred and 65 studies ( = 7,433) were included in the meta-analysis. Results showed negligible to small (d̂ = -.07-.20) effects of affective information on behavioral measures of WM in healthy individuals ( = 4,936) that varied as a function of valence and task-relevance. Heterogeneity analyses were significant, demonstrating the need to identify further study-specific factors and individual differences that moderate affective WM. At the neural level (33 studies; = 683), processing affective versus neutral material during WM tasks was associated with more frequent recruitment of the vlPFC, the amygdala, and the temporo-occipital cortex. In contrast to healthy individuals, across behavioral studies those suffering from mental health problems ( = 2,041) showed impaired WM accuracy (d̂ = -0.21) in the presence of affective material. These findings highlight the importance of integrating behavioral and neural levels of analysis. Finally, these findings suggest that affective WM capacity may be a transdiagnostic mechanism associated with poor mental health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Promoting memory consolidation during sleep: A meta-analysis of targeted memory reactivation.
Hu Xiaoqing,Cheng Larry Y,Chiu Man Hey,Paller Ken A
Targeted memory reactivation (TMR) is a methodology employed to manipulate memory processing during sleep. TMR studies have great potential to advance understanding of sleep-based memory consolidation and corresponding neural mechanisms. Research making use of TMR has developed rapidly, with over 70 articles published in the last decade, yet no quantitative analysis exists to evaluate the overall effects. Here we present the first meta-analysis of sleep TMR, compiled from 91 experiments with 212 effect sizes (N = 2,004). Based on multilevel modeling, overall sleep TMR was highly effective (Hedges' g = 0.29, 95% CI [0.21, 0.38]), with a significant effect for two stages of non-rapid-eye-movement (NREM) sleep (Stage NREM 2: Hedges' g = 0.32, 95% CI [0.04, 0.60]; and slow-wave sleep: Hedges' g = 0.27, 95% CI [0.20, 0.35]). In contrast, TMR was not effective during REM sleep nor during wakefulness in the present analyses. Several analysis strategies were used to address the potential relevance of publication bias. Additional analyses showed that TMR improved memory across multiple domains, including declarative memory and skill acquisition. Given that TMR can reinforce many types of memory, it could be useful for various educational and clinical applications. Overall, the present meta-analysis provides substantial support for the notion that TMR can influence memory storage during NREM sleep, and that this method can be useful for understanding neurocognitive mechanisms of memory consolidation. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Relations of friendship experiences with depressive symptoms and loneliness in childhood and adolescence: A meta-analytic review.
Schwartz-Mette Rebecca A,Shankman Jessica,Dueweke Aubrey R,Borowski Sarah,Rose Amanda J
Well-established psychological theories indicate that interpersonal relationships and emotional well-being are linked in fundamental ways (Coyne, 1976; Sullivan, 1953). Indeed, difficulties in close relationships can contribute to emotional adjustment problems, and emotional problems can adversely affect close relationships. Moreover, different close relationships are especially significant in terms of development and adjustment at different stages of the life span. The current review focuses on childhood and adolescence, developmental stages at which friendships are particularly important. This article presents the results of 16 meta-analyses including 589 unique effects from 233 studies that examine concurrent and longitudinal associations between youths' friendship experiences (number of friends, positive friendship quality, negative friendship quality) and their emotional adjustment (depressive symptoms and loneliness). Studies examining these associations are mixed in regard to whether significant effects emerge. The current research synthesis provides more stable estimates of the effects. In fact, relatively small but significant concurrent and longitudinal associations emerged between the 3 indices of friendship with depressive symptoms and loneliness. The results also suggest that friendship experiences may be more closely linked with loneliness than depressive symptoms and that negative friendship quality may be related to friendship experiences more strongly than number of friends or positive friendship quality. Interestingly, some of the relations were found to be stronger for younger youth. Implications for prevention and intervention efforts are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
The structure of common emotion regulation strategies: A meta-analytic examination.
Naragon-Gainey Kristin,McMahon Tierney P,Chacko Thomas P
Emotion regulation has been examined extensively with regard to important outcomes, including psychological and physical health. However, the literature includes many different emotion regulation strategies but little examination of how they relate to one another, making it difficult to interpret and synthesize findings. The goal of this meta-analysis was to examine the underlying structure of common emotion regulation strategies (i.e., acceptance, behavioral avoidance, distraction, experiential avoidance, expressive suppression, mindfulness, problem solving, reappraisal, rumination, worry), and to evaluate this structure in light of theoretical models of emotion regulation. We also examined how distress tolerance-an important emotion regulation ability -relates to strategy use. We conducted meta-analyses estimating the correlations between emotion regulation strategies (based on 331 samples and 670 effect sizes), as well as between distress tolerance and strategies. The resulting meta-analytic correlation matrix was submitted to confirmatory and exploratory factor analyses. None of the confirmatory models, based on prior theory, was an acceptable fit to the data. Exploratory factor analysis suggested that 3 underlying factors best characterized these data. Two factors-labeled Disengagement and Aversive Cognitive Perseveration-emerged as strongly correlated but distinct factors, with the latter consisting of putatively maladaptive strategies. The third factor, Adaptive Engagement, was a less unified factor and weakly related to the other 2 factors. Distress tolerance was most closely associated with low levels of repetitive negative thought and experiential avoidance, and high levels of acceptance and mindfulness. We discuss the theoretical implications of these findings and applications to emotion regulation assessment. (PsycINFO Database Record
Anxiety and depression as bidirectional risk factors for one another: A meta-analysis of longitudinal studies.
Jacobson Nicholas C,Newman Michelle G
Not only do anxiety and depression diagnoses tend to co-occur, but their symptoms are highly correlated. Although a plethora of research has examined longitudinal associations between anxiety and depression, these data have not yet been effectively synthesized. To address this need, the current study undertook a systematic review and meta-analysis of 66 studies involving 88,336 persons examining the prospective relationship between anxiety and depression at both symptom and disorder levels. Using mixed-effect models, results suggested that all types of anxiety symptoms predicted later depressive symptoms (r = .34), and all types of depressive symptoms predicted later anxiety symptoms (r = .31). Although anxiety symptoms more strongly predicted depressive symptoms than vice versa, the difference in effect size for this analysis was very small and likely not clinically meaningful. Additionally, all types of diagnosed anxiety disorders predicted all types of later depressive disorders (OR = 2.77), and all depressive disorders predicted later anxiety disorders (OR = 2.73). Most anxiety and depressive disorders predicted each other with similar degrees of strength, but depressive disorders more strongly predicted social anxiety disorder (OR = 6.05) and specific phobia (OR = 2.93) than vice versa. Contrary to conclusions of prior reviews, our findings suggest that depressive disorders may be prodromes for social and specific phobia, whereas other anxiety and depressive disorders are bidirectional risk factors for one another. (PsycINFO Database Record
The interpersonal theory of suicide: A systematic review and meta-analysis of a decade of cross-national research.
Chu Carol,Buchman-Schmitt Jennifer M,Stanley Ian H,Hom Melanie A,Tucker Raymond P,Hagan Christopher R,Rogers Megan L,Podlogar Matthew C,Chiurliza Bruno,Ringer Fallon B,Michaels Matthew S,Patros Connor H G,Joiner Thomas E
Over the past decade, the interpersonal theory of suicide has contributed to substantial advances in the scientific and clinical understanding of suicide and related conditions. The interpersonal theory of suicide posits that suicidal desire emerges when individuals experience intractable feelings of perceived burdensomeness and thwarted belongingness and near-lethal or lethal suicidal behavior occurs in the presence of suicidal desire and capability for suicide. A growing number of studies have tested these posited pathways in various samples; however, these findings have yet to be evaluated meta-analytically. This paper aimed to (a) conduct a systematic review of the unpublished and published, peer-reviewed literature examining the relationship between interpersonal theory constructs and suicidal thoughts and behaviors, (b) conduct meta-analyses testing the interpersonal theory hypotheses, and (c) evaluate the influence of various moderators on these relationships. Four electronic bibliographic databases were searched through the end of March, 2016: PubMed, Medline, PsycINFO, and Web of Science. Hypothesis-driven meta-analyses using random effects models were conducted using 122 distinct unpublished and published samples. Findings supported the interpersonal theory: the interaction between thwarted belongingness and perceived burdensomeness was significantly associated with suicidal ideation; and the interaction between thwarted belongingness, perceived burdensomeness, and capability for suicide was significantly related to a greater number of prior suicide attempts. However, effect sizes for these interactions were modest. Alternative configurations of theory variables were similarly useful for predicting suicide risk as theory-consistent pathways. We conclude with limitations and recommendations for the interpersonal theory as a framework for understanding the suicidal spectrum. (PsycINFO Database Record
Brain Oscillations in Sport: Toward EEG Biomarkers of Performance.
Cheron Guy,Petit Géraldine,Cheron Julian,Leroy Axelle,Cebolla Anita,Cevallos Carlos,Petieau Mathieu,Hoellinger Thomas,Zarka David,Clarinval Anne-Marie,Dan Bernard
Frontiers in psychology
Brain dynamics is at the basis of top performance accomplishment in sports. The search for neural biomarkers of performance remains a challenge in movement science and sport psychology. The non-invasive nature of high-density electroencephalography (EEG) recording has made it a most promising avenue for providing quantitative feedback to practitioners and coaches. Here, we review the current relevance of the main types of EEG oscillations in order to trace a perspective for future practical applications of EEG and event-related potentials (ERP) in sport. In this context, the hypotheses of unified brain rhythms and continuity between wake and sleep states should provide a functional template for EEG biomarkers in sport. The oscillations in the thalamo-cortical and hippocampal circuitry including the physiology of the place cells and the grid cells provide a frame of reference for the analysis of delta, theta, beta, alpha (incl.mu), and gamma oscillations recorded in the space field of human performance. Based on recent neuronal models facilitating the distinction between the different dynamic regimes (selective gating and binding) in these different oscillations we suggest an integrated approach articulating together the classical biomechanical factors (3D movements and EMG) and the high-density EEG and ERP signals to allow finer mathematical analysis to optimize sport performance, such as microstates, coherency/directionality analysis and neural generators.
Sleep restriction does not potentiate nocebo-induced changes in pain and cortical potentials.
European journal of pain (London, England)
BACKGROUND:The increased pain sensitivity following reduced sleep may be related to changes in cortical processing of nociceptive stimuli. Expectations shape pain perception and can inhibit (placebo) or enhance (nocebo) pain. Sleep restriction appears to enhance placebo responses; however, whether sleep restriction also affects nocebo responses remains unknown. The aim of the present study was to determine whether sleep restriction facilitates nocebo-induced changes in pain and pain-evoked cortical potentials. METHODS:In an experimental study with a crossover design, the sensitivity to electrically induced pain was determined in 53 nurses under two sleep conditions, after habitual sleep and after two consecutive nights at work. Nocebo was induced by conditioning one-third of the pain stimuli. Pain-elicited cortical event-related potentials were recorded by electroencephalography (EEG). Data were analysed both in the time domain (N2P2 amplitude) and in the time-frequency domain (ERP magnitude). Sleepiness and vigilance were also assessed. RESULTS:Both nocebo alone and sleep restriction alone increased the sensitivity to electrically induced pain. However, no interaction effect was found. Moreover, the magnitude of the pain-elicited responses increased after sleep restriction and decreased after nocebo expectation, suggesting that nocebo is probably not an underlying mechanism for the commonly observed hyperalgesia induced by sleep restriction. CONCLUSIONS:The present work addresses whether sleep restriction, known to increase the sensitivity of the pain system, facilitates nocebo-induced hyperalgesia. Our findings suggest that this is not the case, indicating that the increased sensitivity of the pain system following nocebo and sleep restriction are mediated by different cortical mechanisms.
Neuromarkers of Post-Traumatic Stress Disorder (PTSD) in a patient after bilateral hand amputation - ERP case study.
Chrapusta Anna,Kropotov Juri D,Pąchalska Maria
Annals of agricultural and environmental medicine : AAEM
<b>Introduction</b>. There is a lack in the worldwide literature of reports on the Neuromarkers of Post-Traumatic Stress Disorder (PTSD) in patients after bilateral hand amputation The aim of this study was to test a hypothesis regarding developing Post-Traumatic Stress Disorder (PTSD) in a patient after bilateral hand amputation with the use of Event Related Potentials (ERPs). On the basis of previous research, the amplitudes of P3 ERP components elicited in the cued GO/NOGO tasks have been chosen as candidates for neuromarkers of PTSD. <b>Case study</b>. A 24-year-old patient had undergone bilateral hand amputation 12 months previously. The patient was repeatedly operated on (he had undergone successful bilateral hand replantation) and despite the severity of the injuries, he recovered. However, the patient complained of flashbacks, anxiety and sleep difficulties. Specialist tests showed the presence of PTSD. The patient participated in the cued GO/NOGO task (Kropotov, 2009) with recording 19-channel EEG. P3 GO and NOGO waves in this task were found to be significantly smaller, in comparison to a group of healthy control subjects of the same age (N=23) taken from the HBI normative database (https://www.hbimed.com/). This observed pattern of ERP waves in the patient corresponds to the pattern found in PTSD patients. <b>Conclusions.</b> ERPs in a GO/NOGO task can be used in the assessment of the functional brain changes induced by chronic PTSD.
Effects of caffeine on electrophysiological and neuropsychological indices after sleep deprivation.
Deslandes Andréa,Ferreira Camila,Veiga Heloisa,Cagy Maurício,Piedade Roberto,Pompeu Fernando,Ribeiro Pedro
Caffeine is regarded as a central nervous system (CNS) stimulant. The goal of this study was to analyze electrophysiological, motor, cognitive and behavioral changes produced by caffeine ingestion after sleep deprivation. Ten subjects were evaluated after sleep deprivation, comparing the ingestion of either 400 mg of caffeine or placebo, in a double-blind randomized study. The variables analyzed were: quantitative EEG, the event-related potential (ERP-P300) and cognitive responses. The most significant quantitative EEG results, which were characterized by moment x treatment interactions, were seen in alpha and theta relative power variables. A significant decrease in relative alpha and theta was observed in the caffeine group after sleep deprivation. In relation to caffeine stimulant effects, there were no significant differences in the other parameters.
The use of evoked potentials in sleep research.
Colrain Ian M,Campbell Kenneth B
Sleep medicine reviews
Averaged event-related potentials (ERPs) represent sensory and cognitive processing of stimuli during wakefulness independent of behavioral responses, and reflect the underlying state of the CNS (central nervous system) during sleep. Components measured during wakefulness which are reflective of arousal state or the automatic switching of attention are sensitive to prior sleep disruption. Components reflecting active attentional influences during the waking state appear to be preserved in a rudimentary form during REM sleep, but in a way that highlights the differences in the neurochemical environment between wakefulness and REM sleep. Certain ERP components only appear within sleep. These begin to emerge at NREM sleep onset and may reflect inhibition of information processing and thus have utility as markers of the functional status of sleep preparatory mechanisms. These large amplitude NREM components represent synchronized burst firing of large number of cortical cells and are a reflection of the nervous system's capacity to generate delta frequency EEG activity. As such they are useful in assessing the overall integrity of the nervous system in populations not showing substantial amounts of SWS as measured using traditional criteria. While requiring care in their interpretation, ERPs nonetheless provide a rich tool to investigators interested in probing the nervous system to evaluate daytime functioning in the face of sleep disruption, the ability of the sleeping nervous system to monitor the external environment, and the ability of the nervous system to respond to stimuli in a manner consistent with the initiation or maintenance of sleep.
Event-related potential measures of the inhibition of information processing: II. The sleep onset period.
Campbell Kenneth B,Colrain Ian M
International journal of psychophysiology : official journal of the International Organization of Psychophysiology
The loss of consciousness during the sleep onset period is associated with dramatic changes in information processing. Human event-related potentials (ERPs) reflect these changes. Short- and mid-latency ERPs are only minimally affected by sleep onset. On the other hand, long-latency ERPs are very much affected. A negative wave, N1, peaking at approximately 100 ms gradually decreases in amplitude until it reaches baseline level during definitive stage 2 sleep. The changes in N1 are especially apparent when the subject no longer signals awareness of the external stimulus or when stage 1 is dominated by theta activity in the EEG. The positive peaks, P1 and P2, peaking at approximately 50 and 180 ms, respectively, may appear to increase in amplitude (i.e. also be less negative). A long-lasting processing negativity (PN) may overlap and summate with these peaks during the waking state. During sleep onset, the PN dissipates, thus explaining the apparent positive baseline shift in the ERP waveform. In an oddball task, when an alert and awake subject detects a rare, relevant stimulus, a large positive wave, P300, maximum over parietal areas of the scalp, is observed. This P300 is, however, widely dispersed and can be observed over frontal areas of the scalp. When the subject no longer signals detection of this target stimulus, P300 can no longer be recorded. During stage 1, the parietal P300 remains large, providing the subject overtly detects the target. The amplitude of the frontal aspect of P300 is much reduced as response times slow. This may reflect deactivation of the frontal lobes during the sleep onset period. The infrequent change of an otherwise rapidly presented homogenous train of stimuli is associated with another long-lasting negativity, the mismatch negativity (MMN). The MMN also decreases in amplitude during the sleep onset period, reaching baseline level during definitive sleep. The vertex sharp wave (VSW) becomes apparent during the sleep onset period. Associated with the VSW is a late negative ERP, sometimes called the sleep N2 or the N350, peaking between 300 and 350 ms. It is unique to the sleep onset and sleep periods, becoming very large during stage 1-theta or when the subject no longer shows signs of awareness of the external stimulus.
Sleep extension normalizes ERP of waking auditory sensory gating in healthy habitually short sleeping individuals.
Gumenyuk Valentina,Korzyukov Oleg,Roth Thomas,Bowyer Susan M,Drake Christopher L
Chronic sleep loss has been associated with increased daytime sleepiness, as well as impairments in memory and attentional processes. In the present study, we evaluated the neuronal changes of a pre-attentive process of wake auditory sensory gating, measured by brain event-related potential (ERP)--P50 in eight normal sleepers (NS) (habitual total sleep time (TST) 7 h 32 m) vs. eight chronic short sleeping individuals (SS) (habitual TST ≤6 h). To evaluate the effect of sleep extension on sensory gating, the extended sleep condition was performed in chronic short sleeping individuals. Thus, one week of time in bed (6 h 11 m) corresponding to habitual short sleep (hSS), and one week of extended time (∼ 8 h 25 m) in bed corresponding to extended sleep (eSS), were counterbalanced in the SS group. The gating ERP assessment was performed on the last day after each sleep condition week (normal sleep and habitual short and extended sleep), and was separated by one week with habitual total sleep time and monitored by a sleep diary. We found that amplitude of gating was lower in SS group compared to that in NS group (0.3 µV vs. 1.2 µV, at Cz electrode respectively). The results of the group × laterality interaction showed that the reduction of gating amplitude in the SS group was due to lower amplitude over the left hemisphere and central-midline sites relative to that in the NS group. After sleep extension the amplitude of gating increased in chronic short sleeping individuals relative to their habitual short sleep condition. The sleep condition × frontality interaction analysis confirmed that sleep extension significantly increased the amplitude of gating over frontal and central brain areas compared to parietal brain areas.
Personalized Medicine: Review and Perspectives of Promising Baseline EEG Biomarkers in Major Depressive Disorder and Attention Deficit Hyperactivity Disorder.
Olbrich Sebastian,van Dinteren Rik,Arns Martijn
Personalized medicine in psychiatry is in need of biomarkers that resemble central nervous system function at the level of neuronal activity. Electroencephalography (EEG) during sleep or resting-state conditions and event-related potentials (ERPs) have not only been used to discriminate patients from healthy subjects, but also for the prediction of treatment outcome in various psychiatric diseases, yielding information about tailored therapy approaches for an individual. This review focuses on baseline EEG markers for two psychiatric conditions, namely major depressive disorder and attention deficit hyperactivity disorder. It covers potential biomarkers from EEG sleep research and vigilance regulation, paroxysmal EEG patterns and epileptiform discharges, quantitative EEG features within the EEG main frequency bands, connectivity markers and ERP components that might help to identify favourable treatment outcome. Further, the various markers are discussed in the context of their potential clinical value and as research domain criteria, before giving an outline for future studies that are needed to pave the way to an electrophysiological biomarker-based personalized medicine.
Evidence of sleep-facilitating effect on formation of novel semantic associations: an event-related potential (ERP) study.
Lin Chun-Cheng,Yang Chien-Ming
Neurobiology of learning and memory
Paired-associates learning of unrelated words can reflect the formation of a new association in the semantic network. Research results on the facilitating effect of sleep on unrelated word-pair associates learning remain contradictory. The behavioral measures used in previous studies may not have been sensitive enough to reflect the process of new word association during sleep. The present study used the N400 component of event-related potential (ERP) to further assess the facilitating effect of sleep on the formation of new semantic associations. Thirty subjects were randomly assigned to either the Sleep group or the Wakefulness group. After paired-associates learning and pre-test, they underwent nocturnal sleep and sleep deprivation, respectively. A post-test was conducted after the subjects had one night of recovery sleep. ERPs were recorded during both test phases. Behavioral data showed significant differences in improvements in recognition and decreases in reaction time from pre-test to post-test between the Sleep and Wakefulness groups. The N400 peak amplitude attenuated significantly after sleep, but not after wakefulness. These results suggest that sleep has a facilitating effect on the formation of novel associations. Unexpectedly, slow wave sleep was negatively correlated with improvement in recognition during the post-test but was positively correlated with the number of word-pairs acquired during the learning phase. This may the result of a ceiling effect limiting the improvement achieved in subjects who learned better during the learning phase.
EEG and ERP biomarkers of Alzheimer's disease: a critical review.
Horvath Andras,Szucs Anna,Csukly Gabor,Sakovics Anna,Stefanics Gabor,Kamondi Anita
Frontiers in bioscience (Landmark edition)
Here we critically review studies that used electroencephalography (EEG) or event-related potential (ERP) indices as a biomarker of Alzheimer's disease. In the first part we overview studies that relied on visual inspection of EEG traces and spectral characteristics of EEG. Second, we survey analysis methods motivated by dynamical systems theory (DST) as well as more recent network connectivity approaches. In the third part we review studies of sleep. Next, we compare the utility of early and late ERP components in dementia research. In the section on mismatch negativity (MMN) studies we summarize their results and limitations and outline the emerging field of computational neurology. In the following we overview the use of EEG in the differential diagnosis of the most common neurocognitive disorders. Finally, we provide a summary of the state of the field and conclude that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers. Furthermore, we highlight some practical issues and discuss future challenges as well.