Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis.
BACKGROUND
Bipolar disorder (BD) is a common and debilitating condition, often beginning in adolescence. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis.


METHODS
We analyzed DTI images using tract-based spatial statistics (TBSS), a whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21 adolescents with BD, who also were offspring of at least one parent with BD, and 18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of diffusion anisotropy), trace values (average diffusivity), and apparent diffusion coefficient (ADC; a measure of overall diffusivity) were used as variables in this analysis. In a post hoc analysis, we correlated between FA values, behavioral measures, and medication exposure.


RESULTS
Adolescents with BD had lower FA values than control subjects in the fornix, the left mid-posterior cingulate gyrus, throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital corona radiata bilaterally. There were no significant between-group differences in trace or ADC values and no significant correlation between behavioral measures, medication exposure, and FA values.


CONCLUSIONS
Significant white matter tract alterations in adolescents with BD were observed in regions involved in emotional, behavioral, and cognitive regulation. These results suggest that alterations in white matter are present early in the course of disease in familial BD.
Barnea-Goraly
Naama
N
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Center for Interdisciplinary Brain Sciences Research, Stanford University, 401 Quarry Road, MC 5795, Stanford, CA 94305-5795, USA. naama.barnea-goraly@stanford.edu
Chang
Kiki D
KD
Karchemskiy
Asya
A
Howe
Meghan E
ME
Reiss
Allan L
AL
D000293:Adolescent; D016880:Anisotropy; D001714:Bipolar Disorder / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000002:abnormalities* / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000002:abnormalities* / Q000378:metabolism; D011569:Psychiatric Status Rating Scales