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.

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Available from: Thomas D Geracioti, Nov 13, 2015
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    • "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). "
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    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.
    Full-text · Article · Nov 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
    • "In addition to the abnormalities in the brain structure, recent findings have shown alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning among neglected children in comparison with other types of maltreatment. A study evaluated men with personality disorders, including antisocial disorder, and found a positive relationship between physical and emotional abuse and physical and emotional neglect, specifically between emotional neglect and increased HPA axis function (Lee,Geracioti, Kascow, & Coccaro, 2005). Another study showed that parental neglect and inconsistent discipline may decrease monoamine oxidase A activity, a risk factor for subsequent conduct disorder in adolescence (Foley et al., 2004). "
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    ABSTRACT: The literature has shown that delinquent adolescents report high rates of childhood adversity and family dysfunction. However, it is important to know both the degree of adversity among delinquent adolescents in comparison with other high-risk samples and the contribution of each single form of adversity to this comparison. The purpose of this study was to evaluate childhood adversity, psychopathology, and risk behaviors among 4 high-risk groups, including incarcerated delinquent youths. The participants were 120 male youths between 13 and 19 years old (M = 16.18, SD = 1.26), including 30 youths who were arrested and held in detention centers as a consequence of violent crimes; 30 youths who were identified by Child Protective Services (CPS) and remained with their families; 30 youths who were identified by CPS, removed from their homes, and placed in child and youth residential care; and 30 youths who were randomly selected from schools. The incarcerated youths reported significantly more adversity, global psychopathology, and global index of risk behaviors. When considering each risk behavior, the incarcerated youths reported higher percentages of alcohol abuse, drug use, early smoking initiation, physical assault, carrying weapons, early initiation of sexual intercourse, sexual intercourse under the influence of drugs, and sexual intercourse without condom use. The logistic regression analyses showed that only emotional neglect was significantly associated with delinquency. This study suggests that delinquent youths are exposed to a great magnitude of adversities in childhood, with emotional neglect as an independent risk factor for delinquency. In addition, these youths have higher rates of psychopathology and risk behaviors compared to other high-risk samples.
    No preview · Article · Jul 2015 · Violence and Victims
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    • "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. "
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    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.
    Full-text · Article · Feb 2014 · BMC Psychiatry
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