Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment

Abstract

Context A previous study reported a gene × environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]). Objective To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression. Design Two prospective longitudinal cohort studies. Setting England and New Zealand. Participants Participants in the first sample were women in the E-Risk Study (N= 1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N= 1037), followed up to age 32 years with 96% retention. Main Outcome Measure Research diagnoses of pastyear and recurrent major depressive disorder. Results In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated. Conclusions A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1’s protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume

“…Likewise, the CTQ taps negative events during childhood and adolescence, whereas CFA refers to the first 11 years of life. Similar discrepant G 9 E findings involving the CTQ and objective measures of childhood adversity have previously been reported (Laucht et al 2012;Polanczyk et al 2009). These authors suggested that, instead of the objective occurrence of adverse events, the emotional memories associated with adversity may be important in a gene by adversity interaction with regard to depression.…”

“…While the CTQ assesses memories of different types of childhood maltreatment, CFA covers qualitatively different stressors, which do not address maltreatment directly, but pertain to more adverse family circumstances such as marital discord or early parenthood. Given the role of the amygdala in emotional memory, we expected to find greater effects with regard to the CTQ, which has previously been related to emotional memory reactivation (Polanczyk et al 2009). Second, we extended previous work by investigating connectivity patterns and volumetric differences in the amygdala.…”

FKBP5 and CRHR1 polymorphisms moderate the stress–physical health association in a national sample.

“…FKBP5 has also been associated with an increased risk of depression during adulthood among individuals who suffered from child abuse (Appel et al, 2011). Similarly, SNPs from the corticotrophin-releasing hormone receptor (CRHR1) gene, which helps mediate HPA axis response to stress, have been linked to the onset and course of PTSD in children (Amstadter et al, 2011), as well as increased risk of developing PTSD symptoms and depression during adulthood (Boscarino, Erlich, Hoffman, & Zhang, 2012;Bradley et al, 2008;Polanczyk et al, 2009;Ressler et al, 2010).…”

Em busca das origens desenvolvimentais dos transtornos mentais

“…Entretanto, todas essas técnicas terão sucesso apenas se a avaliação dos fatores ambientais for realizada de forma refinada, com rigor metodológico. Está claro que a forma como as variáveis ambientais é conceitualizada e medida influencia de forma significativa os resultados encontrados 49 . Assim, a avaliação de estressores ambientais deve estar amparada em sólidas bases conceituais.…”