Childhood Trauma and Personality Disorder: Positive Correlation With Adult CSF Corticotropin-Releasing Factor Concentrations

Department of Psychiatry, Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 06/2005; 162(5):995-7. DOI: 10.1176/appi.ajp.162.5.995
Source: PubMed


To test the hypothesis that early life trauma results in adult stress hormone alterations in individuals with personality disorders, the authors examined the relationship between history of childhood adversity and lumbar CSF corticotropin-releasing factor (CRF).
Participants were 20 otherwise healthy men who met DSM-IV criteria for personality disorders. CSF CRF was obtained by lumbar puncture, and childhood adversity was measured by the Childhood Trauma Questionnaire. Correlations were obtained between CSF CRF and the total score on the Childhood Trauma Questionnaire as well as scores on its four subscales.
CSF CRF concentrations were positively correlated with the total score on the Childhood Trauma Questionnaire. Analysis of the subscales revealed that CSF CRF was correlated with emotional neglect. Correlations between CSF CRF level and physical and emotional abuse and with physical neglect were not statistically significant.
Consistent with the hypothesis that the severity of early life stress is correlated with stress hormone abnormalities in adulthood, Childhood Trauma Questionnaire total scores and emotional neglect scores were significantly correlated with CSF CRF levels in individuals with personality disorders.

Download full-text


Available from: Thomas D Geracioti, Nov 13, 2015
  • Source
    • "Significant evidence suggests that CRH plays a role in this process as the central coordinator of the stress response. For instance, CRH is elevated in the cerebrospinal fluid (CSF) of patients diagnosed with PTSD and individuals with significant childhood trauma history (Bremner et al, 1997; Carpenter et al, 2004; Lee et al, 2005). Moreover, CRH receptor type 1 (Crhr1) polymorphisms moderate associations of childhood trauma with depression and anxiety (Bradley et al, 2008; Cicchetti et al, 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although early-life stress is a significant risk factor for developing anxiety disorders, including posttraumatic stress disorder (PTSD), the underlying mechanisms are unclear. Corticotropin releasing hormone (CRH) is disrupted in individuals with PTSD and early-life stress and hence may mediate the effects of early-life stress on PTSD risk. We hypothesized that CRH hyper-signaling in the forebrain during early development is sufficient to increase response to trauma in adulthood. To test this hypothesis, we induced transient, forebrain-specific, CRH over-expression during early-life (pre-puberty, CRHOEdev) in double-mutant mice (Camk2a-rtta2 x tetO-Crh) and tested their behavioral and gene expression responses to the predator stress model of PTSD in adulthood. In one cohort of CRHOEdev exposed and unexposed mice avoidance and arousal behaviors were examined 7-15 days after exposure to predator stress. In another cohort, gene expression changes in Crhr1, Crhr2 and Fkbp51 in forebrain of CRHOEdev exposed and unexposed mice were examined 7 days after predator stress. CRHOEdev induced robust increases in startle reactivity and reductions in startle inhibition independently of predator stress in both male and female mice. Avoidance behaviors after predator stress were highly dependent on sex and CRHOEdev exposure. Whereas stressed females exhibited robust avoidance responses that were not altered by CRHOEdev, males developed significant avoidance only when exposed to both CRHOEdev and stress. qRT-PCR analysis indicated that CRHOEdev unexposed males exhibit significant changes in Crhr2 expression in the amygdala and bed nucleus stria terminalis in response to stress while males exposed to CRHOEdev did not. Similar to CRHOEdev males, females exhibited no significant Crhr2 gene expression changes in response to stress. Cortical Fkbp51 expression was also significantly reduced by stress and CRHOEdev exposure in males, but not in females. These findings indicate that forebrain CRH hyper-signaling in early-life is sufficient to increase enduring effects of adult trauma and attenuate Crhr2 expression changes in response to stress in males. These data support growing evidence for significant sex differences in response to trauma, and support further study of CRHR2 as a candidate mechanism for PTSD risk.Neuropsychopharmacology accepted article preview online, 05 November 2015. doi:10.1038/npp.2015.338.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.338 · 7.05 Impact Factor
  • Source
    • "Previous studies have suggested that childhood neglect could be a predictor of psychopathology, monoamine system dysfunction, and increased cerebrospinal fluid corticotropin-releasing hormone levels in adulthood, when compared with other forms of childhood trauma [16,35,36]. In our study we focused predominantly on the impact of childhood neglect on HPA axis functioning, and Dysfunctional Attitude Scale (DAS) scores. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To date, the relationships between childhood neglect, hypothalamic-pituitary-adrenal (HPA) axis functioning and dysfunctional attitude in depressed patients are still obscure. The Childhood Trauma Questionnaire (CTQ) was used to assess childhood emotional neglect and physical neglect. Twenty-eight depressed patients with childhood neglect and 30 depressed patients without childhood neglect from Guangzhou Psychiatric Hospital were compared with 29 age- and gender-matched control subjects without childhood neglect and 22 control subjects with childhood neglect. Cortisol awakening response, the difference between the cortisol concentrations at awakening and 30 minutes later, provided a measure of HPA axis functioning. The Dysfunctional Attitude Scale measured cognitive schema. HPA axis functioning was significantly increased in depressed patients with childhood neglect compared with depressed patients without childhood neglect (p < 0.001). HPA axis activity in the control group with childhood neglect was significantly higher than in the depressed group without childhood neglect (p < 0.001). Total scores of childhood neglect were positively correlated with HPA axis functioning and dysfunctional attitude scores, but not with severity of depression. We did not find correlations with HPA axis functioning and dysfunctional attitude or with the Hamilton Rating Scale for Depression scores. Childhood neglect may cause hyperactivity of the HPA axis functioning and dysfunctional attitude, but does not affect depression severity.
    BMC Psychiatry 02/2014; 14(1):45. DOI:10.1186/1471-244X-14-45 · 2.21 Impact Factor
  • Source
    • "In additional exploratory analyses, CSF CRH was correlated with peak ACTH, peak cortisol, and the CTQ subscale Emotional Neglect. A focused analysis of the Emotional Neglect subscale of the CTQ was chosen rather than testing of all subscales to preserve statistical power, given our previous finding of a significant positive correlation between the specific CTQ subscale Emotional Neglect with CSF CRH concentration in adult with personality disorder, but a lack of significant correlation with the other CTQ subscales (Physical and Emotional Abuse, Physical Neglect, and Sexual Abuse; Lee et al., 2005). Given the hypothesized directionality, 1-tailed tests were utilized for this test; all other analyses utilized 2-tailed tests given the lack of strong directional hypotheses. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Childhood trauma has been associated with elevated central corticotropin releasing hormone (CRH) drive in adults meeting general DSM-IV criteria for personality disorder. It is not clear how this may be related to pituitary or adrenal responsiveness in personality disorder. It was hypothesized that high levels of childhood trauma would be associated with blunted cortisol and adrenocorticotropin releasing hormone (ACTH) response to the combined dexamethasone(DEX)/CRH test in adults meeting general DSM-IV criteria for personality disorder. 24 healthy, medication free adults with personality disorder (N=16) and a group of healthy controls (N=8) underwent semi-structured diagnostic interviews and completed the Childhood Trauma Questionnaire (CTQ). Across two separate study sessions separated by at least a week, cerebrospinal fluid (CSF) was sampled by lumbar puncture for measurement of CRH concentration (N=17), and peripheral blood cortisol and ACTH levels were measured after challenge with DEX/CRH (N=24). As hypothesized, high CTQ score was associated with a blunted cortisol and ACTH response to DEX/CRH challenge. Indices of cortisol and ACTH response (peak level and area under the curve (AUC)) to DEX/CRH were in turn significantly negatively correlated with CSF CRH concentration. Childhood trauma in adults with personality disorder is associated with blunted cortisol and ACTH secretion following DEX/CRH challenge. These effects are independent of depression or posttraumatic stress disorder. Previous work would suggest that blunted pituitary-adrenal response is related to elevated central CRH drive. Corroborating this, CSF CRH levels were significantly and negatively correlated with peak level and AUC of both cortisol and ACTH.
    Psychoneuroendocrinology 06/2011; 37(1):78-86. DOI:10.1016/j.psyneuen.2011.05.006 · 4.94 Impact Factor
Show more