Elevated CSF Corticotropin-Releasing Factor Concentrations in Posttraumatic Stress Disorder

摘要: Corticotropin-releasing factor (CRF) plays an important role in mediating the mammalian stress response (1). CRF released during (2) from nerve terminals originating paraventricular nucleus of hypothalamus increases secretion adrenocorticotropin hormone (ACTH) anterior pituitary, which turn stimulates release cortisol adrenal (3). Cortisol has a number effects that are beneficial to short-term survival, including suppression reproductive and immune function, promotion analgesia, activation peripheral autonomic system, gastric motility acid secretion, total oxygen consumption glucose glucagon concentrations plasma Chronic results sustained glucocorticoid levels (4), with potentiation responsiveness subsequent stressors (5, 6) neuronal “hypersecretion” CRF. CRF neurons distributed variety locations outside hypothalamus, amygdala, bed stria terminalis, central gray area, locus ceruleus, parabrachial dorsal vagus complex (7). Intraventricular administration laboratory animals behavioral activation, as evidenced by 1) increase EEG activity (8); 2) norepinephrine epinephrine (9, 10); 3) firing site majority noradrenergic cell bodies brain, state increased attention arousal (11); 4) locomotor activity, grooming, rearing (12); 5) behaviors consistent anxiety fear, decrease exploratory open field (13), decreased punished responding conflict test (14), acoustic startle (15, 16). These studies support for fear-related behaviors. Findings clinical relationship among CRF, stress, depression (which been conceptualized chronic disorder). Studies patients consistently reveal CSF blunted ACTH intravenously administered (17–19). Patients posttraumatic disorder (PTSD) have found exhibit alterations hypothalamic-pituitary-adrenal (HPA) axis function (20, 21), although no directly measured PTSD. Somatostatin is tetradecapeptide widespread localization CNS also appears play (22–24). tend covary one another, so it would be predicted associated somatostatin. somatostatin affective disorders, however, either lower than (25–27) or same (28) those comparison subjects (although elevated seen mania [29]). The purpose present study was measure Vietnam combat veterans PTSD matched subjects. We hypothesized