title: Higher in vivo serotonin-1a binding in posttraumatic stress disorder: a PET study with [11C]WAY-100635.
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.
authors: Department of Psychiatry, Columbia University College of Physicians & Surgeons, New York, NY, USA.
authors: Gregory M
authors: GM
authors: Sullivan
authors: R Todd
authors: RT
authors: Ogden
authors: Yung-Yu
authors: YY
authors: Huang
authors: Maria A
authors: MA
authors: Oquendo
authors: J John
authors: JJ
authors: Mann
authors: Ramin V
authors: RV
authors: Parsey
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D011485:Protein Binding / Q000235:genetics; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015415:Biomarkers; D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide