Corticotropin-releasing hormone system polymorphisms are associated with children’s cortisol reactivity

Sheikh, Haroon I.; Kryski, Katie R.; Smith, Heather J.; Hayden, Elizabeth P.; Singh, Shiva M.

doi:10.1016/j.neuroscience.2012.10.056

Cited by 41 publications

(30 citation statements)

References 73 publications

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“…An extensive preclinical literature has supported a role for CRHR1 in depressive and anxiety behaviors (Heim et al, 2009). CRHR1 SNPs have also been associated with anxious temperament and emotion circuit activity in a rhesus macaque model (Rogers et al, 2013) as well as MDD and cortisol reactivity in human studies (Ishitobi et al, 2012;Mahon et al, 2013;Sheikh et al, 2013). In a predominantly African-American sample, Bradley et al (2008) reported an interaction between variants in intron 1 of CRHR1 and a history of child abuse for risk of depressive symptoms, with supportive evidence in a smaller clinical sample of predominantly European-American women.…”

Section: Gene-environment Interactionmentioning

confidence: 99%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

361

243

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Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

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Section: Gene-environment Interactionmentioning

confidence: 99%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

361

243

View full text Add to dashboard Cite

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“…The CRHR1 gene codes for the CRH receptor and variation in CRHR1 genotype has been shown to affect the level of cortisol released in response to laboratory-based stressors in adults (Mahon, Zandi, Potash, Nestadt, & Wand, 2013) and children (Sheikh, Kryski, Smith, Hayden, & Singh, 2013). There is evidence that three single nucleotide polymorphisms (SNPs) in CRHR1 (rs7209436, rs110402, and rs242924) form a protective TAT haplotype.…”

Section: Genes Impacting Hpa Axis Functioningmentioning

confidence: 99%

HPA axis multilocus genetic profile score moderates the impact of interpersonal stress on prospective increases in depressive symptoms for offspring of depressed mothers.

Feurer¹,

McGeary²,

Knopik³

et al. 2017

Journal of Abnormal Psychology

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Although offspring of depressed mothers are at an increased risk for depression themselves, not all of these children develop depression, highlighting the need to identify specific environmental and genetic moderators of risk. The goal of this study was to examine the aggregate influence of genetic polymorphisms associated with the regulation of the hypothalamic-pituitary-adrenal (HPA) axis as a potential moderator of the relation between environmental stress and prospective changes in depressive symptoms for offspring of depressed mothers. Participants were 238 mother-offspring dyads recruited from the community based on the mother’s lifetime history of major depression during the youth’s lifetime (present vs. absent). Mothers and youth completed assessments every 6 months for 2 years (5 total). Results indicated that offspring of depressed mothers showing the greatest increases in depressive symptoms during the follow up were those who had higher HPA multilocus genetic profile scores and who experienced the highest levels of interpersonal stress. These relations were significant for interpersonal stress and were not observed for non-interpersonal stress. These findings suggest that HPA multilocus genetic profile scores may be important genetic markers of stress reactivity and depression risk for offspring of depressed mothers. They also highlight interpersonal stress as a potentially modifiable risk factor for these high-risk youth.

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“…In investigations of adults reporting child maltreatment, cortisol response to the dexamethasone/CRH test was higher among homozygotes for the major allele of rs110402 compared to minor allele carriers (Heim et al, 2009; Tyrka et al, 2009), although this effect was only observed in men in one study (Heim et al, 2009). In a community sample of preschool-aged children, carriers of the minor (A) allele of rs17763104 exhibited greater cortisol reactivity to a stress task compared to major (G) allele homozygotes (Sheikh et al, 2013). CRHR1 has also been associated with diurnal cortisol rhythms.…”

Section: Introductionmentioning

confidence: 99%

CRHR1 genotype and history of maltreatment predict cortisol reactivity to stress in adolescents

Sumner

McLaughlin

Walsh

et al. 2014

Psychoneuroendocrinology

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This study examined the contributions of a polymorphism of the corticotropin-releasing hormone receptor type I (CRHR1)gene (rs110402) and a history of child maltreatment—alone and in interaction—to patterns of cortisol reactivity in adolescents. Adolescents between the age of 13 and 17 years with (n = 61) and without (n = 97) a history of child maltreatment were exposed to the Trier Social Stress Test (TSST). Salivary cortisol was assessed at baseline, and 15 and 30 minutes after the start of the speech portion of the TSST. Saliva samples for genotyping rs110402 also were collected. Adolescents with one or more G alleles of rs110402, relative to A allele homozygotes, and those exposed to maltreatment, relative to non-exposed adolescents, exhibited blunted cortisol reactivity to the TSST (although these associations approached, but did not reach, the level of statistical significance when accounting for underlying population structure in our racially and ethnically diverse sample). There was also a trend for a stronger child maltreatment association with cortisol hypo-reactivity among G allele carriers, but this association was not statistically significant. Findings suggest that CRHR1 variation may moderate the downstream effects of child maltreatment on HPA axis function, and implications for understanding mechanisms of risk associated with early adversity are discussed.

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Corticotropin-releasing hormone system polymorphisms are associated with children’s cortisol reactivity

Cited by 41 publications

References 73 publications

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

HPA axis multilocus genetic profile score moderates the impact of interpersonal stress on prospective increases in depressive symptoms for offspring of depressed mothers.

CRHR1 genotype and history of maltreatment predict cortisol reactivity to stress in adolescents

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