Higher in vivo serotonin-1a binding in posttraumatic stress disorder: a PET study with [11C]WAY-100635

Depress Anxiety. 2013 Mar;30(3):197-206. doi: 10.1002/da.22019. Epub 2013 Feb 13.

Abstract

Background: Brain serotonin-1A receptors (5-HT1A ) are implicated in anxiety. We compared regional brain 5-HT1A binding in medication-free participants with posttraumatic stress disorder (PTSD) and healthy volunteers using fully quantitative positron emission tomography (PET) methods.

Methods: Twenty patients with DSM-IV PTSD (13 with comorbid major depressive disorder, [MDD]) and 49 healthy volunteers underwent PET imaging with 5-HT1A antagonist radioligand [C-11]WAY100635. Arterial blood sampling provided a metabolite-corrected input function and the concentration of free ligand in plasma (fP ) for estimation of regional binding potential, BPF ( = Bavailable / KD ). Linear mixed modeling compared BPF between groups across regions of interest (ROIs).

Results: The PTSD group had higher 5-HT1A BPF across brain ROIs (P = .0006). Post hoc comparisons showed higher 5-HT1A BPF in PTSD in all cortical ROIs (26-33%), amygdala (34%), and brainstem raphe nuclei (43%), but not hippocampus. The subgroup of seven PTSD patients without comorbid MDD had higher 5-HT1A BPF compared with healthy volunteers (P = .03).

Conclusions: This is the first report of higher brainstem and forebrain 5-HT1A binding in vivo in PTSD. The finding is independent of MDD. PTSD and MDD have in common an upregulation of 5-HT1A binding including midbrain autoreceptors that would favor less firing and serotonin release. This abnormality may represent a common biomarker of these stress-associated brain disorders.

Publication types

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

MeSH terms

  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / metabolism
  • Biomarkers / metabolism
  • Brain Stem / diagnostic imaging
  • Brain Stem / metabolism
  • Carbon Radioisotopes
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / metabolism
  • Positron-Emission Tomography / instrumentation
  • Positron-Emission Tomography / methods*
  • Protein Binding / genetics
  • Pyridines / metabolism
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism*
  • Up-Regulation / genetics*

Substances

  • Biomarkers
  • Carbon Radioisotopes
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide