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Biol Psychiatry. 2013 Dec 15;74(12):908-16. doi: 10.1016/j.biopsych.2013.04.010. Epub 2013 May 16.

Impaired anatomical connectivity and related executive functions: differentiating vulnerability and disease marker in bipolar disorder.

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Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Center of Psychosocial Medicine, Heidelberg University, Heidelberg; Department of Clinical Psychology and Neuropsychology, Psychological Institute, Johannes-Gutenberg University Mainz, Mainz, Germany.



Bipolar 1 disorder (BD1) has been associated with impaired set shifting, increased risk taking, and impaired integrity of frontolimbic white matter. However, it remains unknown to what extent these findings are related to each other and whether these abnormalities represent risk factors or consequences of the illness.


We addressed the first question by comparing 19 patients with BD1 and 19 healthy control subjects (sample 1) with diffusion tensor imaging, the Intra-Extra Dimensional Set Shift Task, and the Cambridge Gambling Task. The second question we approached by applying the same protocol to 22 healthy first-degree relatives of patients with BD1 and 22 persons without a family history of mental disorders (sample 2).


In comparison with their control groups, BD1 patients and healthy first-degree relatives of patients with BD1 showed significantly reduced fractional anisotropy (FA) in the right anterior limb of the internal capsule and right uncinate fasciculus. White matter integrity in corpus callosum was reduced in BD1 patients only. In addition, reduced FA in anterior limb of the internal capsule correlated significantly with an increased number of errors during set shifting and increased risk taking and reduced FA in uncinate fasciculus correlated significantly with increased risk taking.


Similar white matter alterations in BD1 patients and healthy relatives of BD1 patients are associated with comparable behavioral abnormalities. Further, results indicate that altered frontolimbic and frontothalamic connectivity and corresponding behavioral abnormalities might be a trait and vulnerability marker of BD1, whereas interhemispheric connectivity appears to be a disease marker.


Bipolar disorder; DTI; first-degree relatives; fractional anisotropy; risk taking; set shifting

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