Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene

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

Will current socioeconomic trends produce a depressing future for men?

The changing economic and social environment of Western nations is having a profound impact on men’s lives. Men who assume a greater share of roles traditionally filled by women will experience challenges to traditional sources of male self-esteem, potentially heightening the risk for depressive disorders among men

The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma

The dexamethasone/corticotropin-releasing factor (CRF) test is considered to be the most sensitive measure of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and has been demonstrated to be altered in patients with major depression (MDD). Although childhood trauma is a demonstrated risk factor for MDD and patients with a history of childhood abuse and MDD demonstrate HPA axis hyperactivity, the dexamethasone/CRF test remains unstudied in this population. We determined the impact of childhood trauma on dexamethasone/CRF test results in patients with MDD. Forty-nine healthy men, ages 18-60 years, without mania or psychosis, active substance abuse, or eating disorder and medication-free were recruited into four study groups, including: 1) normal subjects with no childhood abuse history or psychiatric disorder (n = 14); 2) men with childhood abuse histories without current MDD (n = 14); 3) men with childhood abuse histories with current MDD (n = 15); and 4) men with current MDD and no childhood abuse history (n = 6). Plasma adrenocorticotropin (ACTH) and cortisol concentrations were measured in response to dexamethasone/CRF administration. Men with childhood trauma histories exhibited increases in ACTH and cortisol responses to dexamethasone/CRF compared with non-abused men. In particular, abused men with current MDD showed increased responsiveness compared with control subjects and depressed men without childhood abuse experience. Increased response was associated with the severity, duration, and earlier onset of the abuse. The effects were not explained by concurrent posttraumatic stress disorder. Childhood trauma increases HPA axis activity as measured with the dexamethasone/CRF test in adult men with MDD, potentially reflecting environmental risk for developing depression

Larger amygdala volumes after childhood trauma associated with depression and cortisol response to psychosocial stress in adulthood

Background : Childhood trauma is a major risk factor for the development of affective disorders later in life. We sought to determine whether this risk is linked to neurostructural changes in limbic brain regions after childhood trauma. Methods :We recruited 49 medically healthy adult women (28.2±7.1 years of age) from the Atlanta area to include women with/without childhood trauma and with/without major depression (MDD). Childhood trauma exposure was quantified using the Childhood Trauma Questionnaire (CTQ).Lifetime and current diagnoses of MDD and posttraumatic stress disorder (PTSD) were assessed using the Structured Clinical Interview for DSM-IV (SCID). Current depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Magnetic resonance images were acquired, preprocessed, and registered into stereotactic space. Volume analyses of the left and right amygdala were performed using the interactive software package DISPLAY developed at the Brain Imaging Center of the Montreal Neurological Institute, and a standardized segmentation protocol was applied to outline the anatomical boundaries of the amygdala. Total plasma cortisol responses to the Trier Social Stress Test (TSST) were measured. Results : When stratifying groups by childhood trauma exposure and MDD, women with both childhood trauma and MDD had largest right amygdala volumes compared to all other groups (interaction effect: F=6.172, p= 0.017). Correlational analyses revealed that higher CTQ scores were associated with larger left (r=0.31, p<0.05) and right (r=0.31, p<0.05) amygdala volumes. These correlations remained significant when controlling for age, race, and lifetime diagnoses of MDD and PTSD. Higher CTQ scores were associated with current depression scores (r=0.30, p<0.05), which in turn were positively associated with the size of the right amygdala volume (r=0.32, p<0.05). Finally, the size of the left amygdala was associated with increased cortisol response to the TSST (15 min post TSST: r= 0.44, p< 0.05, 30 min post TSST: r= 0.436, p< 0.05). A similar trend was observed for the right amygdala. Conclusions : These findings add to the growing understanding of the neurobiological basis that may underlie the association between early adverse experience, stress vulnerability, and increased risk for affective disorders

Larger amygdala volumes after childhood trauma associated with depression and cortisol response to psychosocial stress in adulthood

Background : Childhood trauma is a major risk factor for the development of affective disorders later in life. We sought to determine whether this risk is linked to neurostructural changes in limbic brain regions after childhood trauma. Methods :We recruited 49 medically healthy adult women (28.2±7.1 years of age) from the Atlanta area to include women with/without childhood trauma and with/without major depression (MDD). Childhood trauma exposure was quantified using the Childhood Trauma Questionnaire (CTQ).Lifetime and current diagnoses of MDD and posttraumatic stress disorder (PTSD) were assessed using the Structured Clinical Interview for DSM-IV (SCID). Current depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). Magnetic resonance images were acquired, preprocessed, and registered into stereotactic space. Volume analyses of the left and right amygdala were performed using the interactive software package DISPLAY developed at the Brain Imaging Center of the Montreal Neurological Institute, and a standardized segmentation protocol was applied to outline the anatomical boundaries of the amygdala. Total plasma cortisol responses to the Trier Social Stress Test (TSST) were measured. Results : When stratifying groups by childhood trauma exposure and MDD, women with both childhood trauma and MDD had largest right amygdala volumes compared to all other groups (interaction effect: F=6.172, p= 0.017). Correlational analyses revealed that higher CTQ scores were associated with larger left (r=0.31, p<0.05) and right (r=0.31, p<0.05) amygdala volumes. These correlations remained significant when controlling for age, race, and lifetime diagnoses of MDD and PTSD. Higher CTQ scores were associated with current depression scores (r=0.30, p<0.05), which in turn were positively associated with the size of the right amygdala volume (r=0.32, p<0.05). Finally, the size of the left amygdala was associated with increased cortisol response to the TSST (15 min post TSST: r= 0.44, p< 0.05, 30 min post TSST: r= 0.436, p< 0.05). A similar trend was observed for the right amygdala. Conclusions : These findings add to the growing understanding of the neurobiological basis that may underlie the association between early adverse experience, stress vulnerability, and increased risk for affective disorders

Decreased cortical representation of genital somatosensory field after childhood sexual abuse

Sexual dysfunction is a common clinical symptom in women who were victims of childhood sexual abuse. The precise mechanism that mediates this association remains poorly understood. The authors evaluated the relationship between the experience of childhood abuse and neuroplastic thinning of cortical fields, depending on the nature of the abusive experience. The authors used MRI-based cortical thickness analysis in 51 medically healthy adult women to test whether different forms of childhood abuse were associated with cortical thinning in areas critical to the perception and processing of specific behavior implicated in the type of abuse. Exposure to childhood sexual abuse was specifically associated with pronounced cortical thinning in the genital representation field of the primary somatosensory cortex. In contrast, emotional abuse was associated with cortical thinning in regions relevant to self-awareness and self-evaluation. Neural plasticity during development appears to result in cortical adaptation that may shield a child from the sensory processing of the specific abusive experience by altering cortical representation fields in a regionally highly specific manner. Such plastic reorganization may be protective for the child living under abusive conditions, but it may underlie the development of behavioral problems, such as sexual dysfunction, later in life