Cerebrospinal fluid corticotropin-releasing hormone levels are elevated inmonkeys with patterns of brain activity associated with fearful temperament

Background: Asymmetric patterns of frontal brain activity and bl-ain cortic otropin-releasing hormone (CRH) systems hale both been separately implicate d in the processing of normal and abnormal emotional responses. Previous st udies in rhesus monkeys demonstrated that individuals with extreme right fr ontal asymmetric brain electrical activity have high levels of trait-like f earful behavior and increased plasma cortisol concentrations. Methods: In this study we assessed cerebrospinal fluid (CSF) CRH concentrat ions in monkeys with extreme left and extreme right frontal brain electrica l activity. CSF Lt as repeatedly collected at 4, 8, 14, 40, and 52 months o f age. Results: Monkeys with extreme right frontal brain activity had increased CS F CRH concentrations at all ages measured. lit addition, individual differe nces in CSF CRH concentrations were stable from 4 to 52 months of age. Conclusions: These findings suggest that, in primates, the fearful endophen otype is characterized by increased fearful behavior, a specific pattern of frontal electrical activity, increased pituitary-adrenal activity, and inc reased activity of brain CRH systems. Data from other preclinical studies s uggests that the increased brain CRH activity may underlie the behavioral a nd physiological characteristics of fearful endophenotype. (C) 2000 Society of Biological Psychiatry.