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Biol Psychiatry. 2016 Feb 15;79(4):303-10. doi: 10.1016/j.biopsych.2015.03.026. Epub 2015 Apr 6.

Anterior Cortical Development During Adolescence in Bipolar Disorder.

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Departments of Psychiatry, New Haven, Connecticut.
Diagnostic Radiology, New Haven, Connecticut.
Diagnostic Radiology, New Haven, Connecticut.; Electrical Engineering, New Haven, Connecticut.
Diagnostic Radiology, New Haven, Connecticut.; Biomedical Engineering, New Haven, Connecticut.
Departments of Psychiatry, New Haven, Connecticut.; Diagnostic Radiology, New Haven, Connecticut.; Child Study Center, Yale School of Medicine, New Haven, Connecticut.. Electronic address:



Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion.


Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter.


Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p < .05, corrected), including greater gray matter contraction and decreased white matter expansion over time, in the BD compared with the healthy group.


The findings support neurodevelopmental abnormalities during adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter.


Adolescent; Bipolar disorder; Development; Longitudinal studies; Magnetic resonance imaging; Prefrontal cortex

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