1. Inflammation-Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology.
期刊:Biological psychiatry
日期:2022-11-09
DOI :10.1016/j.biopsych.2022.11.003
Findings from numerous laboratories and across neuroimaging modalities have consistently shown that exogenous administration of cytokines or inflammatory stimuli that induce cytokines disrupts circuits and networks involved in motivation and motor activity, threat detection, anxiety, and interoceptive and emotional processing. While inflammatory effects on neural circuits and relevant behaviors may represent adaptive responses promoting conservation of energy and heightened vigilance during immune activation, chronically elevated inflammation may contribute to symptoms of psychiatric illnesses. Indeed, biomarkers of inflammation such as cytokines and acute phase reactants are reliably elevated in a subset of patients with unipolar or bipolar depression, anxiety-related disorders, and schizophrenia and have been associated with differential treatment responses and poor clinical outcomes. A growing body of literature also describes higher levels of endogenous inflammatory markers and altered, typically lower functional or structural connectivity within these circuits in association with transdiagnostic symptoms such as anhedonia and anxiety in psychiatric and at-risk populations. This review presents recent evidence that inflammation and its effects on the brain may serve as one molecular and cellular mechanism of dysconnectivity within anatomically and/or functionally connected cortical and subcortical regions in association with transdiagnostic symptoms. We also discuss the need to establish reproducible methods to assess inflammation-associated dysconnectivity in relation to behavior for use in translational studies or biomarker-driven clinical trials for novel pharmacological or behavioral interventions targeting inflammation or its effects on the brain.
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4区Q3影响因子: 1.5
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2. Inflammation, depression, and anxiety related to recognition memory in young adults.
期刊:The Journal of general psychology
日期:2021-03-17
DOI :10.1080/00221309.2021.1893638
Previous research suggests that common modifiable health risk factors (e.g., depression, anxiety, metabolic illness, inflammation) may have an impact on memory. In the present study, we sought to investigate relationships between a number of these health risk factors and two components of recognition memory (recollection and familiarity). Data were analyzed for 96 healthy young adults between 17 and 25 years old. Recollection and familiarity were measured using an associative recognition procedure involving unitized and unrelated word pairs, and regression analyses were used to relate recognition memory performance to physical health (inflammation via plasma IL-6 levels, central obesity via waste-to-hip ratio, and heart rate variability) and mental health (depression via CESD-R, stress via PSS, and state and personality trait anxiety via STAI) measures of modifiable risk factors. Together, these health variables predicted an additional 19% of the variance in recollection beyond what was accounted for by familiarity, and 15% of the variance in familiarity beyond what was accounted for by recollection. These effects were primarily driven by inflammation, depression, and trait anxiety, which were each significant ( < .05) independent predictors of recognition. Higher levels of depression and inflammation were related to worse recollection yet better familiarity. Higher levels of trait anxiety were related to better recollection but were not related to familiarity. These findings demonstrate complex relationships between these modifiable health risk factors and recognition memory. Future longitudinal and cross-sectional research is needed to further explore these relationships and determine whether or not poor health causes these changes in recognition.
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4区Q1影响因子: 3.8
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3. Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway.
期刊:Environmental epidemiology (Philadelphia, Pa.)
日期:2021-07-01
DOI :10.1097/EE9.0000000000000161
Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.
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1区Q1影响因子: 9.7
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4. Increased maternal non-oxidative energy metabolism mediates association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and offspring autism spectrum disorder symptoms in early life: A birth cohort study.
期刊:Environment international
日期:2022-12-06
DOI :10.1016/j.envint.2022.107678
Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study (BIS), a population-based birth cohort of 1,074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord serum at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured in 596 and 674 children by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) prospective associations between higher prenatal di-(2-ethylhexyl) phthalate (DEHP) levels and upregulation of maternal non-oxidative energy metabolism pathways, and (ii) prospective associations between upregulation of these pathways and increased offspring ASD symptoms at 2 and 4 years of age. Counterfactual mediation analyses indicated that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. These results highlight the importance of the prenatal period and suggest that further investigation of maternal energy metabolism as a molecular mediator of the adverse impact of prenatal environmental exposures such as phthalates is warranted.
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3区Q1影响因子: 3.9
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5. Inflammation, depression, and anxiety disorder: A population-based study examining the association between Interleukin-6 and the experiencing of depressive and anxiety symptoms.
期刊:Psychiatry research
日期:2020-01-25
DOI :10.1016/j.psychres.2020.112809
The uncovering of a positive association between inflammatory cytokine levels - Interkleukin-6 (IL-6) in particular - and the experiencing of depressive and anxiety symptoms is one of the most promising and enthusiastically-discussed finding in recent years. Despite considerable ambiguity in the directionality and underpinnings of this association, anti-inflammatory drugs are already being tested on mental health patients who present no physical symptoms of inflammation, risking potential adverse side effects. Researchers have thus urgently called for more rigorous empirical elucidations of this association. Based on a large, longitudinal, nationally representative sample of middle-aged adults in the United States (N = 1255), IL-6 was observed to be significantly associated with one's present experiencing of depressive and anxiety symptoms. However, IL-6 was predictive of only prospective depressive (not anxiety) symptoms measured six years later, and only when baseline number of symptoms was not accounted for. Further, evidence for IL-6's postulated role as being either a biological cause itself (augmenting HPA stress reactivity) or a biological consequence of a psychological cause (psychological stress) for depression and anxiety was not found. These findings underscore the imperativeness of more rigorous studies to be conducted in this area, and caution practitioners against the premature consideration of IL-6 levels in clinical practice.
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3区Q1影响因子: 3.5
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6. Inflammatory stress responses and future mental health outcomes in people with type 2 diabetes.
期刊:Brain, behavior, & immunity - health
日期:2022-05-23
DOI :10.1016/j.bbih.2022.100472
Background:Inflammatory dysregulation may be linked with mental health disturbances in people with Type 2 Diabetes (T2D), however no previous studies have examined longitudinal associations between inflammatory stress responses and mental health outcomes in T2D. Purpose:To better understand the biological mechanisms that might predispose people with T2D to poor mental health in the future. Methods:At baseline, 140 participants with T2D participated in a laboratory stress testing study (mean age = 64 years). Participants underwent two mental stress tasks and blood was sampled before and up to 45 min post-stress to detect plasma interleukin (IL)-6. The Center for Epidemiological Studies-Depression scale and the Short Form-36 Health Survey were completed at baseline and 7.5 years later. We tested associations between IL-6 stress responses and a) depression symptoms and b) mental health-related quality of life (QoL) at baseline and at follow-up using linear regression analyses adjusting for age, sex, and body mass index (BMI). Results: Up to 66 participants provided follow-up data. In cross-sectional analyses, increased IL-6 stress responses immediately post-task were associated with lower mental health-related quality of life ( = -21.73, = 0.005, 95% CI [-36.82, -6.63]) adjusting for age, sex, and BMI. In longitudinal analyses, increased IL-6 stress responses at 45 min post-task were associated with increased depressive symptoms ( = 10.31 = 0.048, 95% CI [0.10, 20.51]) and decreased mental health-related QoL ( = -21.18 = 0.031, 95% CI [-40.34, -2.02]) adjusting for age, sex, and BMI. The association between the 45-min IL-6 response and depressive symptoms at follow-up was diminished after further adjustment for physical health-related QoL and baseline depressive symptoms ( = 10.14, = 0.055, 95% CI [-0.21,20.48]). Conclusions:This study supports the link between inflammatory stress responsivity and future mental health outcomes in people with T2D. Further research involving a larger sample size is required.
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4区Q2影响因子: 1.3
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7. Association Between Inflammatory Biomarkers and Mental Health Symptoms in Middle Eastern Refugees in the US.
期刊:Cureus
日期:2022-08-21
DOI :10.7759/cureus.28246
INTRODUCTION:Refugees are at increased risk for trauma-related mental health disorders, including anxiety, depression, and post-traumatic stress disorder (PTSD). The underlying biological mechanisms linking trauma to mental disorders need additional study, and the possible pathophysiological role of the immune system is attracting increasing interest. In this study, we investigated whether two well-known pro-inflammatory cytokines (interleukin (IL-8) and IL-6) are associated with mental health symptoms in Middle Eastern refugees displaced to the United States. METHODS:Refugees (n=64, mean age=37.6 years) ages ranged from 21 to 74 years (mean=37.62, SD=11.84) were interviewed one month after arrival in Michigan, United States, using a validated survey in Arabic. Questions covered pre-displacement trauma, current anxiety, depression, and PTSD symptoms. Blood, collected immediately following the interview, was analyzed for the levels of interleukins. Multivariate linear regression was used to determine the association between mental health symptoms and IL-6 and IL-8. RESULTS:In multivariate modeling, older age (β=0.37; p<0.01) and anxiety (β=0.31; p<0.05) were positively associated with IL-8. Age (β=0.28; p<0.05) and pre-displacement trauma (β=0.40; p<0.05) were positively associated with IL-6. Depression (β=-0.38) was negatively associated with IL-6. CONCLUSION/RELEVANCE:This study of inflammatory biomarkers suggests the possibility of differential associations between mental health symptoms (anxiety and depression) and pro-inflammatory markers (IL-6 and IL-8). To enhance our ability to prevent and more effectively treat trauma-exposed refugees, we need to better understand the neuroinflammatory mechanisms contributing to mental disorders.
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3区Q1影响因子: 3.5
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8. Association of serum interleukin-6 and C-reactive protein with depressive and adjustment disorders in COVID-19 inpatients.
期刊:Brain, behavior, & immunity - health
日期:2021-12-11
DOI :10.1016/j.bbih.2021.100405
BACKGROUND:Immune mechanisms are part of the pathophysiology of mental disorders, although their role remains controversial. In depressive disorders a chronic low-grade inflammatory process is observed, with higher interleukin-6 (IL-6) values. Furthermore, in SARS-CoV2 infection, which is closely related to depressive disorders, there is a proinflammatory cascade of cytokines that causes systemic inflammation. METHODS:The present study evaluates the relationship between IL-6 and C-reactive protein (CRP) serum levels and the presence of depressive and adjustment disorders in a sample of 1851 patients admitted to hospital for SARS-CoV2 infection from March to November 2020. Concentrations of IL-6 and CRP were determined within the first 72 h at admission and compared among groups of patients according to previous history and current presence of depression or adjustment disorders. RESULTS:IL-6 serum levels were significantly higher in the group of patients with depression and adjustment disorders compared to patients without such disorders (114.25 pg/mL (SD, 225.44) vs. 86.41 (SD, 202.97)), even after adjusting for several confounders. Similar results were obtained for CRP (103.94 mg/L (SD, 91.16) vs. 90.14 (SD, 85.73)). The absolute levels of IL-6 and CRP were higher than those of previous depression studies, and differences were only found for the subgroup of depressive or adjustment disorders. CONCLUSIONS:Serum concentrations of IL-6 and CRP are higher in COVID-19 patients with but not persistent depressive or adjustment disorders. Clinical features such as fatigue, asthenia, anhedonia, or anxiety can be the basis for this finding.
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2区Q1影响因子: 3.6
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9. Association of serum interleukin-6 with mental health problems in children exposed to perinatal complications and social disadvantage.
作者:Mansur Rodrigo B , Cunha Graccielle R , Asevedo Elson , Zugman André , Rizzo Lucas B , Grassi-Oliveira Rodrigo , Levandowski Mateus L , Gadelha Ary , Pan Pedro M , Teixeira Antônio L , McIntyre Roger S , Mari Jair J , Rohde Luís A , Miguel Eurípedes C , Bressan Rodrigo A , Brietzke Elisa
期刊:Psychoneuroendocrinology
日期:2016-05-17
DOI :10.1016/j.psyneuen.2016.05.015
There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Herein, using data from the High Risk Cohort Study for Psychiatric Disorders, we investigated the relationship between parental mood disorders (PMD), environmental factors, serum interleukin-6 (IL6) and mental health problems in children aged 6-12. We measured the serum levels of IL6 in 567 children. Information related to socio-demographic characteristics, mental health problems and multiple risk factors, as well as parent's psychiatric diagnosis, was captured. We evaluated two groups of environmental risk factors (i.e. perinatal complications and social disadvantage) using a cumulative risk model. Results showed that higher serum levels of IL6 were associated with PMD (RR=1.072, p=0.001), perinatal complications (RR=1.022, p=0.013) and social disadvantage (RR=1.024, p=0.021). There was an interaction between PMD and social disadvantage (RR=1.141, p=0.021), as the effect of PMD on IL6 was significantly higher in children exposed to higher levels of social disadvantage. Moreover, there was a positive correlation between IL6 and mental health problems (RR=1.099, p=0.026), which was moderated by exposure to perinatal complications or social disadvantage (RR=1.273, p=0.015 and RR=1.179, p=0.048, respectively). In conclusions, there is evidence of a differential inflammatory activation in children with PMD and exposure to environmental risk factors, when compared to matched peers. Systemic inflammation may be involved in the pathway linking familial risk and mental health problems.