title: The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding.
abstract: BACKGROUND
  Serotonergic dysfunction is implicated in the pathogenesis of posttraumatic stress disorder (PTSD), and recent animal models suggest that disturbances in serotonin type 1B receptor function, in particular, may contribute to chronic anxiety. However, the specific role of the serotonin type 1B receptor has not been studied in patients with PTSD.
  
  
  OBJECTIVE
  To investigate in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma-exposed control participants without PTSD (TC), and healthy (non-trauma-exposed) control participants (HC) using positron emission tomography and the recently developed serotonin type 1B receptor selective radiotracer [(11)C]P943.
  
  
  METHODS
  Cross-sectional positron emission tomography study under resting conditions.
  
  
  METHODS
  Academic and Veterans Affairs medical centers.
  
  
  METHODS
  Ninety-six individuals in 3 study groups: PTSD (n = 49), TC (n = 20), and HC (n = 27). Main Outcome Measure  Regional [(11)C]P943 binding potential (BP(ND)) values in an a priori-defined limbic corticostriatal circuit investigated using multivariate analysis of variance and multiple regression analysis.
  
  
  RESULTS
  A history of severe trauma exposure in the PTSD and TC groups was associated with marked reductions in [(11)C]P943 BP(ND) in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [(11)C]P943 BP(ND). Developmentally earlier trauma exposure also was associated with greater PTSD symptom severity and major depression comorbidity.
  
  
  CONCLUSIONS
  These data suggest an enduring effect of trauma history on brain function and the phenotype of PTSD. The association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD.
authors: Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, USA. alexander.neumeister@mssm.edu
authors: James W
authors: JW
authors: Murrough
authors: Christoph
authors: C
authors: Czermak
authors: Shannan
authors: S
authors: Henry
authors: Nabeel
authors: N
authors: Nabulsi
authors: Jean-Dominique
authors: JD
authors: Gallezot
authors: Ralitza
authors: R
authors: Gueorguieva
authors: Beata
authors: B
authors: Planeta-Wilson
authors: John H
authors: JH
authors: Krystal
authors: John F
authors: JF
authors: Neumaier
authors: Yiyun
authors: Y
authors: Huang
authors: Yu-Shin
authors: YS
authors: Ding
authors: Richard E
authors: RE
authors: Carson
authors: Alexander
authors: A
authors: Neumeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011760:Pyrrolidinones; D011869:Radioligand Assay / Q000379:methods*; D044302:Receptor, Serotonin, 5-HT1B / Q000096:biosynthesis*; D058829:Serotonin 5-HT1 Receptor Antagonists; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D015599:Trauma Severity Indices; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D002250:Carbon Radioisotopes; D010879:Piperazines; D011760:Pyrrolidinones; D044302:Receptor, Serotonin, 5-HT1B; D058829:Serotonin 5-HT1 Receptor Antagonists