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. OBJECTIVE: Until recently, brain myelin and white matter have not been a major focus of investigation in bipolar patients. Myelin (the white matter insulating the nerves), and factors that affect myelination are processes that could profoundly affect neuronal connectivity. Anatomical magnetic resonance imaging (MRI) studies have shown increased rates of white matter hyperintensities in bipolar disorder, which might be disrupting connectivity among the brain structures implicated in the pathophysiology of this disorder. Recently, reports indicating smaller size and decreased MRI signal intensity in specific sub-regions of corpus callosum (a white matter midline structure that connects the two brain hemispheres, allowing inter-hemispheric communication) in bipolar patients have appeared. These findings suggest the involvement of myelin and white matter abnormalities in the pathophysiology of bipolar disorder. The purpose of this study is to examine whether there are regional myelin abnormalities in white matter brain regions in bipolar patients. RESEARCH PLAN: We propose to utilize a new method to measure myelin integrity, based on the three-pool concept, which proposes that myelin segregates water fractions into myelin, myelinated axons, and mixed pools. The three-pool method successfully estimated the rate and onset of myelination in our preliminary studies. We will study a group of 30 untreated bipolar patients and 30 matched healthy controls, using a 1.9 Tesla MRI magnet. METHODS: We will recruit a group of 30 untreated bipolar patients and 30 healthy controls matched for age, gender and ethnicity, for a total of 60 persons, over a 2-year period, both male and female, ages 18-75. Inclusion criteria for bipolar patients are: a) DSM-IV diagnosis of bipolar disorder type I; b) no substance abuse within the past 6 months; c) no current medical problems; d) not receiving psychotropic medications for at least two weeks at the time of participation in the study; and e) no comorbid psychiatric disorders, except for Anxiety Disorders. Psychiatric diagnosis will be established according to the DSM-IV criteria, using the SCID-IV Interview, and confirmed subsequently in a clinical evaluation by a research psychiatrist. The Hamilton Depression Rating Scale - 17 items and the Young Mania Rating Scale will be used to rate the severity of clinical symptoms. A standard neuropsychological battery will be administered at the time of entrance in the protocol to investigate the possibility of neuropsychological deficits. All subjects will undergo a brain MRI scan, which is performed in a single session and takes 2 hours. All images will be acquired on a large-bore 1.9 T MRI system (Elscint, Haifa, Israel). Statistical analyses will be performed using SPSS version 11.5 software (SPSS, Inc., Chicago, IL). CLINICAL
This study will investigate, for the first time, brain myelin integrity in bipolar disorder, and by doing so, contribute to understanding the disease mechanisms involved. It could ultimately result in the development of new and more effective therapeutic interventions for this disorder.
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