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

Thomas D. Geracioti, Linda L. Carpenter, Michael J. Owens, Dewleen G. Baker, Nosakhare N. Ekhator, Paul S. Horn, Jeffrey R. Strawn, Gerard Sanacora, Becky Kinkead, Lawrence H. Price, Charles Nemeroff

Research output: Contribution to journalArticlepeer-review


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, cross-over 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.

Original languageEnglish
Pages (from-to)637-643
Number of pages7
JournalAmerican Journal of Psychiatry
Issue number4
StatePublished - Apr 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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