GENETIC UNDERPINNINGS OF BRAIN ABNORMALITIES IN MOOD DISORDERS

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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: This protocol is a companion to the currently approved IRB protocols for the brain imaging studies in bipolar and unipolar disorders conducted by Dr. Jair Soares' research group. For every consenting patient who participates in Dr. Soares' imaging protocols, a blood sample will be collected for future genetic studies, which will begin to explore the relevance of specific genetic polymorphisms, as those are identified, in brain abnormalities that will be identified through these ongoing imaging studies (imaging endophenotypes). RESEARCH PLAN: We will enroll 540 patients who will participate in our imaging studies. This is an add-on study that involves obtaining a blood sample for future genetic studies. Once patients agree to participation in the imaging protocols, they will be offered the possibility of participating in the add-on genetics study through this specific protocol. This study will start to examine the genetic underpinnings of in vivo anatomical and neurochemical brain abnormalities in mood disorder patients. Such abnormalities are currently being identified in our ongoing imaging studies, and as these brain imaging studies evolve, may turn out to be useful imaging endophenotypes for future genetic investigations in mood disorders. This study will be an add-on to our currently approved imaging protocols, and its main goal will be exploratory, as very little is known about specific genetic polymorphisms that modulate brain abnormalities in these illnesses. METHODS: The specific aims of the proposed study are: (1) Examine whether currently identified polymorphisms for the baring-derived neurotrophic factor (BDNF) are associated with anatomical and neurochemical brain abnormalities in fronto-limbic brain circuits identified in bipolar and unipolar mood disorder subjects; (2) As new polymorphisms for genes involved in brain development, or genes that modulate signal transduction pathways, and dopaminergic and serotonergic pathways in the brain are identified, we want to examine, on an exploratory basis, whether such polymorphisms are associated with anatomical and neurochemical brain imaging abnormalities in bipolar and unipolar mood disorder subjects. CLINICAL RELEVANCE: Once we have accumulated a larger sample of bipolar and unipolar patients and healthy individuals from our ongoing imaging studies, and have a better understanding of most promising imaging endophenotypes in these patients, we will be able to start examining the influence of specific genes that regulate brain development on the identified brain abnormalities. This protocol can be greatly relevant to help elucidate genetic underpinnings of brain abnormalities in mood disorders.