Project 3: Neurobiological Characterization of Offspring of Biopolar Parents

University Of Cincinnati, Cincinnati OH

Investigators

Linked publications & trials

Abstract

Despite the significant morbidity and mortality associated with bipolar disorder, the neurophysiological[unreadable] basis of the development of this illness is poorly understood. Adolescence is the most common period of[unreadable] onset of bipolar disorder. Moreover, offspring of bipolar parents have an elevated risk of developing bipolar[unreadable] disorder compared with the general population. Therefore, one approach toward clarifying[unreadable] neurodeveloprriental models of the early progression of bipolar disorder and identifying potential[unreadable] neurobiological predictors of incipient mood episodes is to study young subjects who are at risk for[unreadable] developing bipolar disorder (i.e., have a bipolar parent), but do not yet have a mood disorder themselves.[unreadable] Bipolar disorder is characterized by disruption of mood and attention. The anterior limbic network, which[unreadable] involves the ventral prefrontal cortex, thalamus, amygdala, and striatum, appears to regulate these these[unreadable] processes. Consequently, we hypothesize that the symptoms of bipolar disorder arise from dysfunction[unreadable] within this network. Specifically, functional imaging (fMRI) studies suggest that the anterior limbic network[unreadable] may be excessively activated in bipolar patients, thereby producing the symptoms of this condition.[unreadable] Additionally, magnetic resonance spectroscopy (MRS) studies suggest that hypermetabolism may underlie[unreadable] the excessive anterior limbic activation. Specifically, MRS studies have found that bipolar patients exhibit[unreadable] excessive glutamate (Glu) and myoinositol (ml) concentrations compared with healthy subjects.[unreadable] With these consideration in mind, the goals of this study are: 1) To use fMRI and 1H MRS to assess[unreadable] functional and metabolic anterior limbic abnormalities in adolescent and young adult offspring of bipolar[unreadable] parents (at-risk); 2) To use fMRI and 1H MRS to evaluate functional and metabolic anterior limbic[unreadable] abnormalities as potential markers for incipient mood disorders in at-risk adolescents and young adults; and[unreadable] 3) To examine the progression of anterior limbic abnormalities in at-risk adolescents and young adults who[unreadable] develop a mood disorder. In order to accomplish these aims, we will acquire neurometabolic (MRS) and[unreadable] neurofunctional (fMRI) measurements in 140 subjects without any mood disorder and with a bipolar parent[unreadable] (at-risk, AR) and 40 subjects without a first-degree relative with a mood disorder (healthy, HC) for the[unreadable] proposed longitudinal study. Comparisons between offspring of bipolar and healthy parents will define[unreadable] baseline fMRI and 1H MRS abnormalities and longitudinal follow-up of both groups will identify predictors and[unreadable] markers of incipient mood episodes, as well as neurodevelopmental changes that are unique to the[unreadable] development of mood episodes in those at risk for bipolar disorder (Center Goals 1-3). We believe this[unreadable] information may ultimately, clarify neurophysiological models of bipolar disorder (Center Goal 1) and provide[unreadable] neurophysiological treatment targets in order to prevent the onset of bipolar disorder in those with a familial[unreadable] risk for developing the illness (Center goals 2 & 3).