Abstract
Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18–77 years and 18–45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR × environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 × child abuse interactions.
Highlights
It is well-established that adverse experience early in life, such as childhood abuse, neglect or loss, dramatically increases the risk of developing major depression in adulthood, in the context of additional challenge (Bifulco et al, 1991; McCauley et al, 1997; Dube et al, 2001; Chapman et al, 2004)
Our results suggest that the corticotropin-releasing hormone receptor 1 (CRHR1) gene may only moderate the effects of specific types of childhood trauma on depression
In men who had been exposed to physical abuse, 30.4% had experienced sexual abuse, while this proportion was much higher in females, with 62.8%
Summary
It is well-established that adverse experience early in life, such as childhood abuse, neglect or loss, dramatically increases the risk of developing major depression in adulthood, in the context of additional challenge (Bifulco et al, 1991; McCauley et al, 1997; Dube et al, 2001; Chapman et al, 2004). (Ladd et al, 2000; Meaney and Szyf, 2005; Heim et al, 2008b; Lupien et al, 2009; McGowan et al, 2009) These persistent neurobiological consequences of early-life stress have been hypothesized to mediate the vulnerability to adult depression in victims of childhood trauma. Not all individuals who experience childhood trauma develop depression and some individuals remain resilient even when exposed to additional stressors in adolescence or adulthood. Particular attention has been directed towards the role of a functional polymorphism in the promoter region of the serotonin transporter gene (5HTTLPR) in moderating the effects of childhood stress on adult depression (Caspi et al, 2003; Brown and Harris, 2008), though results are inconsistent across studies (Brown and Harris, 2008). A recent meta-analysis failed to corroborate the role of the 5HTTLPR in moderating the link between life stress and depression (Risch et al, 2009), though space constraints preclude a comprehensive discussion of Frontiers in Behavioral Neuroscience www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
