Low cerebrospinal fluid and plasma orexin-A (hypocretin-1) concentrations in combat-related posttraumatic stress disorder.
The hypothalamic neuropeptide, orexin-A has a number of regulatory effects in humans and pre-clinical evidence suggests a link to neuroendocrine systems known to be pathophysiologically related to posttraumatic stress disorder (PTSD). However, there are no reports of central nervous system (CNS) or peripheral orexin-A concentrations in patients with PTSD, or any anxiety disorder. Cerebrospinal fluid (CSF) and plasma levels of orexin-A were serially determined in patients with PTSD and healthy comparison subjects to characterize the relationships between orexin-A (in the CNS and peripheral circulation) and central indices of monoaminergic neurotransmission and to determine the degree to which CNS orexin-A concentrations reflect those in the circulating blood. CSF and plasma samples were obtained serially over a 6-h period in 10 male combat veterans with chronic PTSD and 10 healthy male subjects through an indwelling subarachnoid catheter. Orexin-A concentrations were determined in plasma and CSF and CSF levels of the serotonin metabolite, 5-hydroxyindolacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid (HVA), were determined over the sampling period. CSF and plasma orexin-A concentrations were significantly lower in the patients with PTSD as compared with healthy comparison subjects at all time points. In addition, CSF orexin-A concentrations strongly and negatively correlated with PTSD severity as measured by the Clinician-Administered PTSD Scale (CAPS) in patients with PTSD. Peripheral and CNS concentrations of orexin-A were correlated in the healthy comparison subjects and peripheral orexin-A also correlated with CNS serotonergic tone. These findings suggest low central and peripheral orexin-A activity in patients with chronic PTSD are related to symptom severity and raise the possibility that orexin-A is part of the pathophysiological mechanisms of combat-related PTSD.
Strawn
Jeffrey R
JR
Department of Psychiatry, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0559, USA. strawnjr@uc.edu
Pyne-Geithman
Gail J
GJ
Ekhator
Nosakhare N
NN
Horn
Paul S
PS
Uhde
Thomas W
TW
Shutter
Lori A
LA
Baker
Dewleen G
DG
Geracioti
Thomas D
TD
D000328:Adult; D003130:Combat Disorders / Q000097:blood* / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000097:blood* / Q000134:cerebrospinal fluid*; D000068797:Orexins; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000134:cerebrospinal fluid*; D014728:Veterans; D055815:Young Adult
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid