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Tyrka A.R.,Mood Disorders Research Program | Tyrka A.R.,Brown University | Kelly M.M.,Mood Disorders Research Program | Kelly M.M.,Brown University | And 6 more authors.
Psychoneuroendocrinology | Year: 2010

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been observed in association with internalizing symptoms and is thought to be involved in the pathogenesis of depression and some anxiety disorders. This study examined basal and stress-induced cortisol concentrations in relation to internalizing and externalizing symptoms in a racially mixed community sample of 102 8-11-year-old boys. Afternoon basal cortisol concentrations were positively correlated with measures of internalizing behavior problems, social problems, and emotionality. Greater change in cortisol across a home-visit challenge task was also significantly associated with internalizing behaviors and social problems, as well as attention and thought problems. The implications of these findings and how they may relate to the pathogenesis of emotional and behavioral problems are discussed. © 2010 Elsevier Ltd. Source

Carpenter L.L.,Mood Disorders Research Program | Carpenter L.L.,Brown University | Gawuga C.E.,Brown University | Tyrka A.R.,Mood Disorders Research Program | And 3 more authors.
Acta Psychiatrica Scandinavica | Year: 2012

Objective: To determine whether C-reactive protein (CRP) can serve as a marker for alterations in immune function prior to the manifestation of significant psychiatric and medical disorders. Method: Ninety-two healthy adults were recruited from the community and determined to be free of psychiatric or medical disorders. The concentration of plasma CRP from a single resting sample was examined in relation to current mental and physical health as well as to self-reported history of early life adversity. Results: C-reactive protein showed a significant positive correlation with body mass index (BMI; r=0.477, P<0.001). Non-specific pain, fatigue, and lower overall quality of physical health were all associated with higher CRP concentrations (all P<0.05 or P<0.01), after controlling for effect of BMI and other relevant covariates. Subthreshold depression symptoms and other indices of mental/emotional wellbeing were not associated with CRP, nor was CRP significantly linked to any measures of early life adversity. Conclusion: Lower-quality physical health and wellbeing, but not the presence of mood/anxiety symptoms or early life stress (ELS), were significantly related to plasma CRP. Elevated CRP does not appear to be a fundamental consequence of ELS among healthy adults. © 2012 John Wiley & Sons A/S. Source

Carpenter L.L.,Mood Disorders Research Program | Carpenter L.L.,Brown University | Gawuga C.E.,Brown University | Tyrka A.R.,Mood Disorders Research Program | And 5 more authors.
Neuropsychopharmacology | Year: 2010

Increased production of peripheral cytokines and other pro-inflammatory markers has been linked to psychiatric disorders such as major depressive disorder and post-traumatic stress disorder. Recent research has pointed to early-life stress, particularly childhood maltreatment, as an independent and preventable risk factor for systemic inflammation in adulthood. Some data suggest that adults with a history of childhood maltreatment exhibit a heightened inflammatory response to acute stress challenge. To further elucidate the relationship between childhood maltreatment and pro-inflammatory cytokine production, we examined plasma IL-6 response to the Trier Social Stress Test (TSST) in 69 healthy adult subjects without depression or post-traumatic stress disorder. Serial plasma IL-6 concentrations were measured during a standardized psychosocial stressor in n=19 subjects with moderate-severe childhood maltreatment (MAL), and n=50 controls without maltreatment (CTL), as indicated by self-ratings on the childhood trauma questionnaire (CTQ). CTQ total scores were positively correlated with overall change in IL-6 response, as well as the maximum IL-6 concentration during the TSST. Greater acute IL-6 release and higher IL-6 concentrations over time were observed for the MAL group relative to the CTL group. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult physical and mental health. The results of this preliminary study warrant further investigation in a larger sample. © 2010 Nature Publishing Group All rights reserved. Source

Tyrka A.R.,Mood Disorders Research Program | Tyrka A.R.,Brown University | Parade S.H.,Brown University | Parade S.H.,Bradley Hasbro Childrens Research Center | And 10 more authors.
Translational Psychiatry | Year: 2016

Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene. © The Author(s) 2016. Source

Tyrka A.R.,Mood Disorders Research Program | Tyrka A.R.,Brown University | Walters O.C.,Mood Disorders Research Program | Price L.H.,Mood Disorders Research Program | And 4 more authors.
Hormone and Metabolic Research | Year: 2012

Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic- pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease. © Georg Thieme Verlag KG Stuttgart New York. Source

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