Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD

Biol Psychiatry. 2000 Mar 15;47(6):526-39. doi: 10.1016/s0006-3223(99)00185-7.


Background: Consistent with many studies demonstrating enhanced reactivity of the sympathetic nervous system in posttraumatic stress disorder (PTSD), the administration of yohimbine, a noradrenergic alpha(2)-antagonist, has been shown to increase core symptoms of PTSD and to induce greater increases in plasma 3-methyl-4-hydroxy-phenyl-glycol (MHPG) in subjects with PTSD compared with healthy control subjects. In turn, neuropeptide Y (NPY) has been shown to inhibit the release of norepinephrine from sympathetic noradrenergic neurons.

Methods: In the following study, plasma NPY responses to yohimbine and placebo were measured in a subgroup of 18 subjects with PTSD and 8 healthy control subjects who participated in the previous study of the effect of yohimbine on plasma MHPG.

Results: The PTSD subjects had lower baseline plasma NPY and blunted yohimbine-stimulated increases in plasma NPY compared with the healthy control subjects. Within the PTSD group, baseline plasma NPY levels correlated negatively with combat exposure scale scores, baseline PTSD and panic symptoms, and yohimbine-stimulated increases in MHPG and systolic blood pressure.

Conclusions: This study suggests that combat stress-induced decreases in plasma NPY may mediate, in part, the noradrenergic system hyperreactivity observed in combat-related PTSD. The persistence of this decrease in plasma NPY may contribute to symptoms of hyperarousal and the expression of exaggerated alarm reactions, anxiety reactions, or both in combat veterans with PTSD long after war.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / blood*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Adult
  • Blood Pressure / drug effects
  • Heart Rate / drug effects
  • Humans
  • Male
  • Methoxyhydroxyphenylglycol / metabolism
  • Neuropeptide Y / metabolism*
  • Panic Disorder / blood
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Stress Disorders, Post-Traumatic / blood*
  • Stress Disorders, Post-Traumatic / diagnosis
  • Warfare
  • Yohimbine / blood*
  • Yohimbine / pharmacology*


  • Adrenergic alpha-Antagonists
  • Neuropeptide Y
  • Yohimbine
  • Methoxyhydroxyphenylglycol