Cerebrospinal Fluid Corticotropin-Releasing Factor and Perceived Early-Life Stress in Depressed Patients and Healthy Control Subjects

Abstract

Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not. Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans.

CSF Corticotropin-Releasing Factor in Personality Disorder: Relationship with Self-Reported Parental Care

“…Although it could also be argued that PD subjects, who score higher on measures of stress reactivity such as neuroticism, are more sensitive than other subjects to the psychological stress of lumbar puncture. Mean CRF concentration in the PD group (39.9727.8 pg/ml) was comparable to those reported previously in clinical populations with depression (Carpenter et al, 2004), anxiety disorder (Fossey et al, 1996), acute alcohol withdrawal (Adinoff et al, 1996), schizophrenia (Nishino et al, 1998), in PTSD with and without psychosis (Sautter et al, 2003), and as measured by serial sampling in PTSD (Baker et al, 1999). It is of interest that CRF values in our normal controls (27.1713.2 pg/ml) are comparable to those reported by Carpenter et al (2004) (24.978.6 pg/ml).…”

“…This is accounted for by the significant restriction of range in PBI Care scores to the higher end in normal, non-PD samples; a larger sample would be necessary to adequately address the relationship between parental care and adult CSF CRF levels in normal controls. Of note, a previous investigation did find a relationship between CSF CRF and a different measure of early life stress in healthy volunteers not screened for PD (Carpenter et al, 2004). If PD does not determine CSF CRF level, what is the clinical relevance of CSF CRF in PD?…”

“…In a sample of adult depressives and normal controls subjects, early life stress in the preschool years predicted higher CSF CRF concentration, while preteen and perinatal early life stress was associated with decreased CSF CRF concentration. The finding was not driven by the presence of depression (Carpenter et al, 2004). We recently reported an analysis of male PD subjects who completed the childhood trauma questionnaire (CTQ).…”

“…Convergent human data is available from two published cross-sectional reports of a positive relationship between cerebrospinal fluid (CSF) level of corticotropin-releasing factor (CRF) and history of childhood abuse and/or neglect. The first found that in depressed and normal control subjects, cerebrospinal fluid (CSF) level of CSF CRF, but not depressive disorder, was positively related to level of early childhood parental abuse and/or neglect as measured by a questionnaire measure of perceived early life stress (Global perceived early life stress; Carpenter et al, 2004). We subsequently reported that in a sample of 20 male PD subjects, CSF CRF was positively correlated with Childhood Trauma Questionnaire total and the Emotional Neglect subscale score (Lee et al, 2005).…”

Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

“…CRF appears to be important to the pathophysiology of stress-related disorders such as post-traumatic stress disorder (PTSD) and depression; elevated levels of cerebrospinal fluid (CSF) CRF have been identified in both of these disorders (Bremner et al, 1997;Gold and Chrousos, 2002). Early life stress has also been associated with alterations in adult CSF CRF levels, in both preclinical and clinical studies (Carpenter et al, 2004;Heim et al, 2004), and recent study results indicate that that early life stress influences stress system function in adults with FM (McLean et al, 2005b;Weissbecker et al, 2005). In the single study assessing CRF levels in FM patients to date, Riedel et al (2002) found higher baseline serum CRF levels in FM patients vs healthy controls.…”