IN VIVO BRAIN MECHANISMS ACROSS THE BIPOLAR SPECTRUM

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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: The specific aim of this study is to begin to test the hypothesis that brain abnormalities in fronto-limbic brain (FLB) regions in bipolar spectrum patients (BD I, BD II, BD NOS and cyclothymia) are distributed along a continuum, which reflects the spectrum of clinical symptoms seen in these patients with more pronounced abnormalities in BD type I. We will focus on generating preliminary information on the neurobiological differentiation between BD I, BD II, BD NOS and cyclothymia. In particular, we will examine the following predictions: (a) BD I, BD II, BD NOS and cyclothymic patients will have lower gray matter volumes in the anterior cingulated volumes compared to healthy controls; (b) BD I, BD II,BD NOS and cyclothymic patients will have larger amygdala volumes compared to healthy controls; (c) BD I, BD II, BD NOS and cyclothymic patients will have lower levels of NAA (N-Acetyl Aspartate, measured by MRS) in dorsolateral prefrontal cortex (PFC) compared to healthy controls; and (d) FLB abnormalities (decrease in gray matter anterior cingulated volumes, enlargement of the amygdala, and decrease in NAA levels in dorsolateral PFC) will be more pronounced in BD type I compared to BD II, BD NOS and cyclothymia. RESEARCH PLAN: We will conduct an in vivo neuroimaging study of 30 BD I, 30 BD II, 30 BD NOS and 30 cyclothymic patients, to examine the neurobiological mechanisms involved across bipolar spectrum disorders (BSD). This will generate preliminary data to test the hypothesis that brain abnormalities in FLB regions in BSD patients are distributed along a continuum, which reflects the spectrum of clinical symptoms seen in these patients. METHODS: We will recruit 30 BD I, 30 BD II, 30 BD NOS and 30 cyclothymic patients, and 120 healthy controls. Patients will be matched for age, gender, race, and years of education. Patients (BD sub-types I, II, NOS and cyclothymia, according to DSM-IV criteria, will be off medications for at least two weeks at the time they enroll in the study, not in an acute phase of the illness, and will not have any co-morbid axis I psychiatric disorders, except for anxiety disorders, binge eating disorder and substance disorders in remission for at least six months. The specific inclusion criteria for BD patients across the 4 patient groups are: (a) diagnosis of BD I, II, NOS or cyclothymia based on DSM-IV criteria; (b) ages 18-65 years old; (c) not currently in an acute illness episode (HAMD 12 and YMRS 12); (d) off all psychotropic medications for at least two weeks. Exclusion criteria will be: (a) presence of any axis I psychiatric comorbid disorder, except for anxiety disorders, binge eating disorder and substance disorders in remission for at least six months; (b) current major medical problems; (c) history of neurologic disorders, including head injury with loss of consciousness; (d) family history of hereditary neurologic disorders; (e) floating metallic objects in the body (exclusion for MR studies); and (f) non English speaking. The healthy controls (n=120) will be matched to the patients for age, gender, race and years of education. Inclusion criteria: (a) no lifetime or present history of any axis I psychiatric disorder, based on DSM-IV criteria; (b) ages 18-65 years old; (c) no use of any psychoactive medication in the past two weeks before enrollment in the study. CLINICAL RELEVANCE: BSD are a major health problem in the US and throughout the world, with an estimated prevalence of 3%-6.5%. These disorders have a substantial economic impact; in 1998, their estimated cost to US society was 24 billion dollars. The sub-threshold manifestations of BD, often classified as BD NOS, or even more broadly as bipolar spectrum, are also impairing, and produce substantial suffering and disability, as documented in recent studies. Moreover, it has become increasingly evident that the categorical definitions currently used for these manifestations may not be adequate. Brain mechanisms involved in the various BSD sub-types may be common, with variations in the specific profile and degree to which specific structures may be involved. Therefore, clinical neuroscience studies that focus on BSD are much needed, as a novel strategy likely to identify specific mechanisms implicated in these disorders.