The Effect of Early Trauma Exposure on Serotonin Type 1B Receptor Expression Revealed by Reduced Selective Radioligand Binding

Mood and Anxiety Disorders Program, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, USA.
Archives of general psychiatry (Impact Factor: 14.48). 09/2011; 68(9):892-900. DOI: 10.1001/archgenpsychiatry.2011.91
Source: PubMed


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.
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.
Cross-sectional positron emission tomography study under resting conditions.
Academic and Veterans Affairs medical centers.
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.
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.
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.

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    • "mean composite [11C]OMAR VT values were computed by averaging [11C]OMAR VT values across all brain regions for each individual. A series of analyses of covariance (ANCOVA) were then conducted to test for group differences in mean composite [11C]OMAR VT values, as well as in regions that comprise the amygdala-hippocampal-cortico-striatal circuit implicated in PTSD41. In these analyses, group (HC, TC, and PTSD) and sex were entered as independent variables, age as a covariate, and [11C]OMAR VT values as the dependent variable. "
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