Elevated cortisol levels and increased rates of diabetes and mood symptoms in Soviet Union-born Jewish immigrants to Germany

Korenblum, W.; Barthel, Andreas; Licinio, Júlio; Wong, Ma-Li; Wolf, Oliver T.; Kirschbaum, Clemens; Bornstein, Stefan R.

doi:10.1038/sj.mp.4001720

Cited by 30 publications

(30 citation statements)

References 13 publications

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“…These critical environmental factors have been used in the present work to help minimize the inclusion of genetically susceptible individuals in the control sample. Our Mexican-American cohort is comprised of first-generation individuals (60%) 23 who have experienced significant levels of stress and hyperactivation of the hypothalamic-pituitary-adrenal axis related to acculturation issues; 24,25 therefore, our Mexican-American controls were “supernormal” individuals resilient to significant levels of enduring stress; in our replication cohort the stress levels in controls were also included in our analyses. Furthermore, as most of the variations reported here in the Mexican-American cohort were rare, each gene contained low-frequency mutations at many different sites, which could help explain the challenges experienced in this field, as the power of association studies in MDD have been greatly reduced because the critical assumption that there were little allelic heterogeneity within loci may not apply; 79 this assumption may have been harder to negate in populations of European-Ancestry due to their drastically reduced number of SNVs (Tables 3 and S3).…”

Section: Discussionmentioning

confidence: 99%

“…Unique features of this study include: 1) a cohort of cases and controls comprised of Mexican-Americans of the greater Los Angeles area who were mainly recent immigrants born in Mexico 23 and who experienced significant levels of hyperactivation of the hypothalamic-pituitary-adrenal axis related to challenges, distress, and acculturation issues related to immigration; 24,25 2) type of genetic variations studied; 3) an ethnically diverse replication cohort with stress level data in controls. We performed whole genome screening specifically of functional variants to investigate whether our experimental design could contribute to explain the ‘missing heritability’ of MDD.…”

Section: Introductionmentioning

confidence: 99%

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The PHF21B gene is associated with major depression and modulates the stress response

et al. 2016

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Major depressive disorder (MDD) affects around 350 million people worldwide, however the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder in which stress is a critical component, and used whole genome screening of functional variants to investigate the ‘missing heritability’ in MDD. GWAS analyses using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-Ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-Ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide FDR<0.05), and their pathway analysis revealed that the three top overrepresented GO processes were innate immune response, glutamate receptor signalling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the PHF21B gene in the ethnically unrelated European-Ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole genome sequencing analyses of a subset of the cohorts revealed that European-Ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared to Mexican-American individuals and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress, when compared to non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The PHF21B gene is associated with major depression and modulates the stress response

et al. 2016

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“…Emerging evidence shows that moving from one society to another bears an increased risk for both obesity and mood disorder associated with elevated stress hormones. 5 Indeed, the alarmingly high rates of both disorders points to a connection between the two and that realization has triggered major funding agencies in the US and Europe to request research projects to explain the relationship between depression and obesity in modern society. 6 The HPA axis as a distal mediator of gene-environment interactions Stress is conveyed in the body in many ways.…”

Section: Introductionmentioning

confidence: 99%

Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions

et al. 2006

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Obesity and depression are serious public health problems and also constitute cardiovascular disease risk factors. Research organizations have called for efforts to explore the interrelationship between obesity and depression. A useful starting point is the fact that in both disorders there is dysregulation of stress systems. We review molecular and clinical evidence indicating that the mediators of the stress response are a key locus for geneenvironment interactions in the shared biology of depression and obesity. Scientific milestones include translational paradigms such as mice knockouts, imaging and pharmacogenomic approaches that can identify new therapeutic strategies for those burdened by these two afflictions of contemporary civilization. Perspectives for the future are promising. Our ability to dissect the underpinnings of common and complex diseases with shared substrates will be greatly enhanced by the Genes and Environment Initiative, the emerging Large Scale Studies of Genes and Environment in Common Disease, and the UK Biobank Project.

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“…For example, traditional models of stress and stress adaptation, particularly that of Selye (1976), suggest that the cumulative ''wear and tear'' associated with emotional distress may eventually trigger allostatic mechanisms that increase the risk of illness and disease. Indeed, allostatic changes associated with enduring hypothalamic-pituitary-adrenal axis activation and concomitant elevations in cortisol Clin Psychol Med Settings (2012) 19:197-210 205 secretion include detrimental immunological processes, such as immunosuppression or excessive levels of proinflammatory cytokines (e.g., IL-6) (Robles, Glaser, & Kiecolt-Glaser, 2005), as well as increased risks of cardiovascular diseases (al'Absi & Wittmers, 2003;Flipovsky, Ducimetaere, Eschwaege, Richard, Rosselin, & Claude, 1996), diabetes (Korenblum et al, 2005;Roy, Roy, & Brown, 1998), osteoporosis (Chiodini et al, 2007), peptic ulcers (Lechin et al, 1990), and autoimmune diseases (Straub et al, 2004). As negative affect is considered to subsume negative emotions, such as depression (Watson & Clark, 1984;Watson, Clark, & Carey, 1988;Watson, Clark, & Tellegen, 1988), and increased secretion of cortisol is one of the best documented biological correlates of depression, it is perhaps not coincidental that the prevalence of the disorders mentioned previously is high among people with depression (Evans et al, 2005;Sherwood Brown, Varghese, & McEwen, 2004).…”

Section: Discussionmentioning

confidence: 99%

Associations Between Positive and Negative Affect and 12-Month Physical Disorders in a National Sample

Weiser

2012

J Clin Psychol Med Settings

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Associations between positive and negative affect and a range of 12-month physical disorders were investigated in the Midlife Development in the United States Survey, a nationally representative sample of 3,032 adults ages 25-74. These associations were examined, controlling for relevant sociodemographic and psychiatric covariates. High positive affect was associated with decreased risk of physical disorders, whereas high negative affect was associated with increased risk. However, associations between positive affect and physical disorders were partially attenuated following adjustment for concurrent negative affect. Additionally, high affect balance was associated with decreased risk of physical disorders before and after adjustments. These findings underscore the relevance of affective disposition in health status, suggesting that both positive and negative affect may serve as viable health risk parameters.

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Elevated cortisol levels and increased rates of diabetes and mood symptoms in Soviet Union-born Jewish immigrants to Germany

Cited by 30 publications

References 13 publications

The PHF21B gene is associated with major depression and modulates the stress response

The PHF21B gene is associated with major depression and modulates the stress response

Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions

Associations Between Positive and Negative Affect and 12-Month Physical Disorders in a National Sample

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