Elevated cerebrospinal fluid substance p concentrations in posttraumatic stress disorder and major depression.
OBJECTIVE
The authors tested the hypothesis that concentrations of the pain-transmitting neuropeptide substance P are elevated in the CSF of patients with major depression or posttraumatic stress disorder (PTSD), which have overlapping symptoms. The authors also sought to determine if CNS substance P concentrations change on provocation of symptoms in PTSD patients.


METHODS
The authors measured CSF substance P concentrations in medication-free patients with either major depression or PTSD and in healthy comparison subjects. Next, using a within-subject, crossover design, the authors sampled CSF for 6 hours through an indwelling subarachnoid catheter in PTSD patients before, during, and after exposure to a 60-minute traumatic or neutral videotape stimulus.


RESULTS
Both depressed and PTSD patients had significantly elevated basal CSF substance P concentrations. In the challenge study, marked increases in CSF substance P concentrations were found only after precipitation of PTSD symptoms. CSF substance P concentrations increased by 169% and 90.6% of baseline levels at 10 and 70 minutes, respectively, after the start of the traumatic videotape but changed by only 1.1% and -8.1% of baseline levels 10 and 70 minutes after the start of the neutral videotape.


CONCLUSIONS
These results suggest that elevated CNS substance P concentrations are involved in both major depression and PTSD. The marked increase in CSF substance P concentrations during and after the symptom-provoking stimulus, but not after the neutral stimulus, implicates CNS release of substance P in the mechanism of acute PTSD symptoms. These data also reveal that CNS substance P responds acutely to psychological stress in humans.
Geracioti
Thomas D
TD
Research Service, VA Medical Center, 3200 Vine St, Box 151, Cincinnati, OH 45220, USA. Thomas.Geracioti@med.va.gov
Carpenter
Linda L
LL
Owens
Michael J
MJ
Baker
Dewleen G
DG
Ekhator
Nosakhare N
NN
Horn
Paul S
PS
Strawn
Jeffrey R
JR
Sanacora
Gerard
G
Kinkead
Becky
B
Price
Lawrence H
LH
Nemeroff
Charles B
CB
D000208:Acute Disease; D000328:Adult; D001143:Arousal / Q000502:physiology; D002408:Catheters, Indwelling; D003130:Combat Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000523:psychology; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology; D006801:Humans; D008016:Life Change Events; D008297:Male; D010507:Periodicity; D010775:Photic Stimulation / Q000379:methods; D013129:Spinal Puncture; D013313:Stress Disorders, Post-Traumatic / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology; D013315:Stress, Psychological / Q000134:cerebrospinal fluid / Q000209:etiology / Q000523:psychology*; D013346:Subarachnoid Space; D013373:Substance P / Q000134:cerebrospinal fluid*; D014743:Videotape Recording; D014796:Visual Perception / Q000502:physiology
D013373:Substance P