Sex, trauma, stress hormones and depression

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N ¼ 18 cases/18 controls) and a test cohort (N ¼ 11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.

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“…Only male subjects were used to reduce the known confound of sex-steroids on GR activation (Young and Korszun, 2010).…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Menke

Arloth

Pütz

et al. 2012

Neuropsychopharmacol

150

126

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“…These gender differences could be explained by several factors. The sensitivity to PS differs between men and women (Young and Korszun, 2010). Overall, men are more physically active (Zitouni and Guinhouya, 2012;Peer et al, 2013).…”

Section: Discussionmentioning

confidence: 94%

Impact of Interactions Between Self-Reported Psychological Stress and Habitual Exercise on the Dietary Intake of Japanese Men and Women: a Large-Scale Cross-Sectional Study

Endoh

Kuriki²,

Kasezawa³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Modifying lifestyle factors such as diet and exercise can reduce the risk of cancer. Psychological stress (PS) might be indirectly associated with cancer because it alters lifestyle factors. However, the relationship among these variables has not been fully investigated. Thus, we examined interactions between self-reported PS (SRPS) and habitual exercise on diet. Materials and Methods: In all, 5,587 men and 2,718 women were divided SRPS levels: low, moderate and high. Diet was estimated using a validated food frequency questionnaire. Using a general linear model, food and nutrient consumption was estimated for each SRPS level in the 2 exercise groups, and the interactions between SRPS levels and exercise were calculated. Results: In women, the intake of pork and beef, low fat milk and yogurt, natto (fermented soybean), carrots and squash, other root vegetables, mushrooms, genistein, carotene, retinol equivalents, vitamin B2, pantothenic acid, potassium, calcium, magnesium, phosphorus Conclusions: We suggest that certain foods and nutrients, which are thought to have a protective effect against cancer, interact with SRPS and habitual exercise, especially in women. This information is valuable for understanding and improving interventions for cancer prevention.

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“…Childhood sexual abuse has also been strongly linked to psychiatric risk (Felitti et al 1998;Kendler et al 2002;Nelson et al 2002;Kendler et al 2004;Kendler et al 2006;Fergusson et al 2008). Though the mechanisms involved are not yet entirely clear, there is mounting evidence that these associations between adverse childhood experiences and psychiatric risk are mediated by permanent effects of repeated stressors on HPA axis reactivity (Heim et al 2008;Pariante and Lightman 2008;Lupien et al 2009;Romeo 2010;Young and Korszun 2010). Several studies have shown elevated rates of childhood sexual abuse and risky family environment in nonheterosexuals (Cameron and Cameron 1995;Lenderking et al 1997;Fergusson et al 1999;Paul et al 2001;Tomeo et al 2001;Balsam et al 2005;Arreola et al 2008;Alanko et al 2009;Zietsch et al in press).…”

Section: Adverse Childhood Experiences -Risky Family Environment and mentioning

confidence: 99%

Explanations for Elevated Psychiatric Vulnerability in Nonheterosexuals: Environmental Stressors, Genetics, and the HPA and HPG Axes

Zietsch¹

2011

Psychiatric Disorders - Worldwide Advances

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Sex, trauma, stress hormones and depression

Cited by 198 publications

References 53 publications

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Impact of Interactions Between Self-Reported Psychological Stress and Habitual Exercise on the Dietary Intake of Japanese Men and Women: a Large-Scale Cross-Sectional Study

Explanations for Elevated Psychiatric Vulnerability in Nonheterosexuals: Environmental Stressors, Genetics, and the HPA and HPG Axes

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