Family study of brain abnormalities in bipolar disorder

Abstract

Our proposal will examine the heritability of specific brain abnormalities that are present in individuals suffering from bipolar disorder. We will attempt to identify specific phenotypes from in vivo brain imaging that could be possible trait markers of vulnerability for the disease. The two most consistently replicated findings from in vivo imaging studies with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in bipolar patients are enlargement of amygdala and reduced levels of N-acetyl Aspartate (NAA) in dorsolateral prefrontal cortex (PFC). We hypothesize that such abnormalities are trait markers of the illness, and that they could also be found to some extent in non-affected siblings of bipolar patients. On an exploratory basis, we will also examine whether there are specific genes related to brain development that would confer vulnerability for the identified brain abnormalities. We will recruit a group of 40 individuals affected with bipolar disorder, type I, and 40 non-affected siblings of bipolar patients, ages 18-75 years old, both males and females. The study will be conducted over a 2-year period. Bipolar patients, their siblings, and healthy individuals without a family history of psychiatric illness will be matched for age, gender, educational level, and race. Patients will be diagnosed according to the DSM-IV criteria. A MRI/MRS scan will be conducted at a 1.5T Phillips MR scanner. Morphometric measurements of specific brain regions involved in mood regulation (sub-genual prefrontal cortex, dorsolateral prefrontal cortex, and amygdala), as well as neurochemical measures of the levels of NAA in dorsolateral prefrontal cortex will be obtained. This work has the potential to help understand the possible heritability of specific in vivo anatomical and neurochemical brain abnormalities that are possibly involved in the pathophysiology of bipolar disorder. Our results could contribute to identify specific trait markers related to vulnerability to this illness, which could eventually assist in identifying specific sub-groups of individuals who are at higher risk for developing the illness, and for whom more targeted interventions could be of benefit. (AU)