Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder.

Department of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA.
American Journal of Psychiatry (Impact Factor: 13.56). 06/1997; 154(5):624-9.
Source: PubMed

ABSTRACT Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects.
Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N = 11) and comparison subjects (N = 17). CSF concentrations of CRF and somatostatin were compared between the two groups.
CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean = 29.0 pg/ml, SD = 7.8, versus mean = 21.9 pg/ml, SD = 6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean = 19.9 pg/ml, SD = 5.4, versus mean = 13.7 pg/ml, SD = 8.0). However, covarying for age reduced the level of significance.
Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain. Copyright © 2014. Published by Elsevier B.V.
    Brain Research 12/2014; 1599. DOI:10.1016/j.brainres.2014.12.038 · 2.83 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the interaction between fear and reward at the circuit and molecular level has implications for basic scientific approaches to memory and for understanding the etiology of psychiatric disorders. Both stress and exposure to drugs of abuse induce epigenetic changes that result in persistent behavioral changes, some of which may contribute to the formation of a drug addiction or a stress-related psychiatric disorder. Converging evidence suggests that similar behavioral, neurobiological, and molecular mechanisms control the extinction of learned fear and drug-seeking responses. This may, in part, account for the fact that individuals with Post-Traumatic Stress Disorder have a significantly elevated risk of developing a Substance Use Disorder and have high rates of relapse to drugs of abuse, even after long periods of abstinence. At the behavioral level, a major challenge in treatments is that extinguished behavior is often not persistent, returning with changes in context, the passage of time, or exposure to mild stressors. A common goal of treatments is therefore to weaken the ability of stressors to induce relapse. With the discovery of epigenetic mechanisms that create persistent molecular signals, recent work on extinction has focused on how modulating these epigenetic targets can create lasting extinction of fear or drug-seeking behavior. Here, we review recent evidence pointing to common behavioral, systems, and epigenetic mechanisms in the regulation of fear and drug seeking. We suggest that targeting these mechanisms in combination with behavioral therapy may promote treatment and weaken stress-induced relapse.
    Genes Brain and Behavior 01/2015; 14(1). DOI:10.1111/gbb.12187 · 3.51 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014