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Presentation Time: 10:40-11:00
Home University: UNC-Chapel Hill
Research Mentor: Patrick Sullivan, Psychiatry
Program: CSS
Research Title: Assessing Transcriptional and Epigenetic Impacts of Antipsychotics

Schizophrenia is a severe mental disorder that affects ~1% of the population. It is typically diagnosed during adolescence or early adulthood, and characterized by the presence of hallucinations, delusions, and grossly disorganized behavior. Antipsychotics are the primary treatment of these symptoms. Unfortunately, due to side effects, and/or lack of efficacy, about 75% of patients discontinue the use of antipsychotics. This study uses functional genomics approaches to gain mechanistic insight into the transcriptional and epigenetic changes brought about by chronic antipsychotic exposure. We carried out a dosage study (pilot study) using drug-containing chow, to determine the appropriate dose needed to achieve human-like plasma drug levels of commonly used antipsychotics. The study consisted of 8-week old male C57BL/6 mice that were randomized across 3 different treatment groups: haloperidol (1 mg/kg; 3 mg/kg; 5 mg/kg), olanzapine, and placebo (n=4 mice per treatment group). Mice were fed drug-containing chow for a period of 28 days; plasma was collected at 21 days. Body weight was recorded before and after treatment. Haloperidol treatment groups 3 mg/kg and 5 mg/kg were discontinued due to weight loss. After 28 days, mice went through cardiac perfusion, and brain regions were dissected and stored at -80°C. Dosage studies will be followed with larger groups of mice and additional antipsychotics, in order to elucidate the effects of chronic antipsychotic treatment on chromatin structure and gene expression.