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The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding.

Abstract

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

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  • Authors

    Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot JD, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding YS, Carson RE, Neumeister A

    Source

    Archives of general psychiatry 68:9 2011 Sep pg 892-900

    MeSH

    Adolescent
    Adult
    Age Factors
    Brain
    Carbon Radioisotopes
    Cross-Sectional Studies
    Depressive Disorder, Major
    Female
    Humans
    Male
    Middle Aged
    Piperazines
    Positron-Emission Tomography
    Psychiatric Status Rating Scales
    Pyrrolidinones
    Radioligand Assay
    Receptor, Serotonin, 5-HT1B
    Serotonin 5-HT1 Receptor Antagonists
    Stress Disorders, Post-Traumatic
    Trauma Severity Indices
    Wounds and Injuries

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21893657