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In this report, we seek to (i) identify a potential neuroimaging endophenotype for bipolar disorder (BD) in emotion regulatory and autonomic circuitry in young first-degree relatives of persons with BD; and (ii) replicate our previous work identifying the functional neuroanatomy of working memory (WM) in an older sample of relatives of persons with BD.Ten adolescent and young adult (age 13-24) unmedicated, non-ill, first-degree relatives of persons with BD (RELS) and 10 demographically comparable healthy controls performed a 2-back WM task and a 0-back control task during functional magnetic resonance imaging (fMRI). fMRI data were collected on a 1.5 Tesla scanner and analyzed using SPM-2. Mood was assessed on the day of scanning.The groups did not differ on any demographic, neuropsychological, or in-scanner task performance variables. In contrast to controls, RELS showed (i) weak task-dependent modulation activity in the cerebellar vermis (CV), insula, and amygdala/parahippocampal region, and (ii) exaggerated modulation of activity in the frontopolar cortex and brainstem, even after controlling for potential confounders. Many of the group differences were driven by differences in activity in the low-level (0-back) baseline task.Young, unmedicated RELS exhibited altered task-dependent modulation of frontopolar, CV, and insula activity during WM, especially during the low-level (0-back) baseline task. Results are largely consistent with our initial study of older adult RELS, suggesting these alterations may represent biomarkers of genetic risk for BD.

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. © 2010 Wiley-Liss, Inc.