This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVES: The proposed research will examine the role of the neurosteroid, allopregnanolone, in modulating the anxiety and distress experienced by subjects with posttraumatic stress disorder (PTSD). RESEARCH PLAN: Twenty PTSD and control subjects will be studied on four days occurring at least 5 days apart. Single doses of two medications will be used to experimentally manipulate neurosteroid levels. Subjective and psychological reactivity to trauma cues will serve as primary outcome measures. METHODS: PTSD will be studied to determine the effect of diagnosis on baseline and trauma script induced levels of cortisol, progesterone, and allopregnanolone. Single daily doses of olanzapine, an atypical antipsychotic which has been reported to increase levels of allopregananolone in rats and which is used to treat PTSD, will be examined for its ability to reduce trauma cue induced anxiety and distress. Single daily doses of finasteride, a 5-alpha reductase inhibitor that prevents allopregnanolone synthesis, will be used to determine the portion of olanzapine effects attributable to allopregnanolone. Olanzapine and finasteride will be administered under double blind conditions using a 2x2 factorial design. Trauma cue reactivity will be measured using an established script driven imagery procedure. CLINICAL
This study will increase our knowledge of the role of neurosteroids in the pathogenesis of PTSD and the therapeutic actions of medications used to treat PTSD. It will also extend our understanding of the importance of alterations in steroid hormone synthesis frequently observed in PTSD subjects.
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