Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder.
ABSTRACT Post-traumatic stress disorder (PTSD) is often comorbid with major depressive episodes (MDEs) and both conditions carry a higher rate of suicidal behavior. Hypothalamic-pituitary-adrenal (HPA) axis and serotonin abnormalities are associated with both conditions and suicidal behavior, but their inter-relation is not known. We determined cortisol response to placebo or fenfluramine in MDE, MDE and PTSD (MDE+PTSD), and healthy volunteers (HVs) and examined the relation of cortisol responses to suicidal behavior. A total of 58 medication-free patients with MDE (13 had MDE+PTSD) and 24 HVs were studied. They received placebo on the first day and fenfluramine on the second day. Cortisol levels were drawn before challenge and for 5 h thereafter. The MDE+PTSD group had the lowest plasma cortisol, the MDE group had the highest, and HVs had intermediate levels. There were no group differences in cortisol response to fenfluramine. Suicidal behavior, sex, and childhood history of abuse were not predictors of baseline or postchallenge plasma cortisol. Cortisol levels increased with age. This study finds elevated cortisol levels in MDE and is the first report of lower cortisol levels in MDE+PTSD. The findings underscore the impact of comorbidity of PTSD with MDE and highlight the importance of considering comorbidity in psychobiology.
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ABSTRACT: Childhood abuse and neglect are known to affect psychological states through behavioral, emotional, and cognitive pathways. They increase the risk of having psychiatric diseases in adulthood and have been considered risk factors for suicidal behavior in all diagnostic categories. Early, prolonged, and severe trauma is also known to increase impulsivity, diminishing the capacity of the brain to inhibit negative actions and to control and modulate emotions. Many neurobiological studies hold that childhood maltreatment may lead to a persistent failure of the inhibitory processes ruled mainly by the frontal cortex over a fear-motivated hyperresponsive limbic system. Multiple neurotransmitters and hormones are involved in the stress response, but, to our knowledge, the two major biological consequences of the chronic exposure to trauma are the hypofunction of the serotonergic system and changes in the hypothalamic-pituitary-adrenal axis function. Some of these findings overlap with the neurobiological features of impulsivity and of suicidal behavior. Impulsivity has also been said to be both a consequence of trauma and a risk factor for the development of a pathological response to trauma. Thus, we suggest that impulsivity could be one of the links between childhood trauma and suicidal behavior. Prevention of childhood abuse could significantly reduce suicidal behavior in adolescents and adults, in part, through a decrease in the frequency of impulsive behaviors in the future.Comprehensive psychiatry 51(2):121-9. · 2.08 Impact Factor