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:
The aim of this study is to determine if neuropsychological and structural MRI abnormalities identified in BPD patients are present in their unaffected siblings, raising the potential that these measures could be used as endophenotypes for BPD. RESEARCH PLAN AND METHODS: 1. Apply a neuropsychological battery of tests of attention, executive function, and working and declarative memory to 20 sibling pairs discordant for BPD (20 BPD patients and 20 of their siblings) and 20 matched healthy subjects. We hypothesize that these measures will be impaired in BPD patients, and to a lesser degree, to their unaffected siblings. 2. Acquire high quality Structural MRI images, using a Siemens 3 Telsa MRI scanner, in this same sample to better define the prefrontal and medial temporal/limbic abnormalities associated with BPD. We hypothesize that abnormalities in the prefrontal cortex will be sensitive to genetic liability for BPD and will explore the possibility that amygdale anomalies are associated with risk for BPD. CLINCAL
Twin family and adoption studies have demonstrated that bipolar disorder (BPD) is substantially heritable. Yet, despite considerable evidence that risk for BPD is inherited, the molecular genetic basis for this illness remains elusive. Given evidence that genes predisposing to BPD may be transmitted without expression of the clinical phenotype, interest has arisen in developing indicators of processes mediating between genotype and phonotype. Such allied phenotypes, or endophenotypes, may directly index the underlying pathology, or liability to disease, and hence can be measured in both affected and unaffected individuals. These markers are often quantitative, which will allow for analysis strategies that have not been available for qualitative phenotypic markers. The ultimate promise of developing endophenotypic markers for BPD is to facilitate the search for genetic loci associated with the disorder and in the isolation of environmental contributions to illness expression among genotype carriers, possibly leading to prevention or treatment strategies.
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