Elevated cerebrospinal fluid substance p concentrations in posttraumatic stress disorder and major depression

Am J Psychiatry. 2006 Apr;163(4):637-43. doi: 10.1176/ajp.2006.163.4.637.


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.

Method: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Arousal / physiology
  • Catheters, Indwelling
  • Combat Disorders / cerebrospinal fluid
  • Combat Disorders / diagnosis
  • Combat Disorders / psychology
  • Cross-Over Studies
  • Depressive Disorder, Major / cerebrospinal fluid*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / psychology
  • Humans
  • Life Change Events
  • Male
  • Periodicity
  • Photic Stimulation / methods
  • Spinal Puncture
  • Stress Disorders, Post-Traumatic / cerebrospinal fluid*
  • Stress Disorders, Post-Traumatic / diagnosis
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / cerebrospinal fluid
  • Stress, Psychological / etiology
  • Stress, Psychological / psychology*
  • Subarachnoid Space
  • Substance P / cerebrospinal fluid*
  • Videotape Recording
  • Visual Perception / physiology


  • Substance P