Dysfunctional decision-making related to white matter alterations in bipolar I disorder

Objective: This study investigated how frontal white matter (WM) alterations in patients with bipolar I disorder (BD-I) are linked to motivational dysregulation, often reported in the form of risk-taking and impulsivity, and whether structure-function relations in patients might differ from healthy subjects (HC).

Method: We acquired diffusion data from 24 euthymic BD-I patients and 24 controls, to evaluate WM integrity of selected frontal tracts. Risk-taking was assessed by the Cambridge Gambling Task and impulsivity by self-report with the Barratt-Impulsiveness Scale.

Results: BD-I patients displayed significantly lower integrity in the right cingulum compared to HC. They also showed more risk-taking behavior and reported increased trait-impulsivity. Risk-taking was negatively associated with WM integrity in the right cingulum. Impulsivity was not related to WM integrity in investigated tracts. Together with age and sex, FA in the cingulum explained 25% of variance in risk-taking scores in all study participants. The left inferior fronto-occipital fasciculus (IFOF) was specifically predictive of risk-taking behavior in BD-I patients, but not in HC.

Limitations: The employed parameters did not allow us to specify the exact origin of WM changes, nor did the method allow the analysis of specific brain subregions. Also, sample size was moderate and the sample included patients with lifetime alcohol dependence/abuse, hence effects found need replication and have to be interpreted with caution.

Conclusion: Our results further strengthen recent models linking structural changes in frontal networks to behavioral markers of BD-I. They extend recent findings by showing that risk-taking is also linked to the cingulum in BD-I and HC, while other prefrontal tracts (IFOF) are specifically implicated in risk-taking behavior in BD-I patients. Meanwhile, self-reported impulsivity was not associated with WM integrity of the tracts investigated in our study.