Cingulum Bundle White Matter in Bipolar Disorder: Relationship With Impulsivity and Suicide Attempt

Bipolar disorder (BD) has one of the highest suicide rates among mental disorders. Although the frontolimbic brain network has been implicated in both BD and suicide, the neurobiological mechanisms underlying suicide in BD remain poorly understood. In this study, we examined frontolimbic white matter microstructure and its link to suicide attempts (SAs) in BD in 2 independent samples.

The initial cohort comprised U.S. military veterans with BD with an SA history (BD/SA+) (n = 21) or without an SA history (BD/SA-) (n = 23). Fractional anisotropy (FA) in the cingulum cingulate (CGC), cingulum hippocampus (CGH), and uncinate fasciculus (UF) was examined using diffusion tensor imaging and correlated with the Urgency, Premeditation, Perseverance, Sensation-Seeking, and Positive Urgency (UPPS-P) Impulsive Behavior Scale. We sought to replicate neuroimaging findings in an independent population-based sample of 44 BD/SA+ and 321 BD/SA- participants from the UK Biobank (UKB).

Compared with the BD/SA- group, the BD/SA+ group in the U.S. veterans sample demonstrated lower FA in the CGH (p = .036, η_p² = 0.111), which was associated with greater impulsivity (negative urgency domain; r_s = -0.318, p = .035). We replicated the finding of lower FA in the CGH in the BD/SA+ group compared with the BD/SA- group (p = .010, η_p² = 0.019) in the UKB sample. FA did not differ in the CGC or UF between attempters and nonattempters in either sample.

Consistent findings in 2 independent samples from different demographic backgrounds suggest that lower putative white matter integrity in the CGH is associated with SAs in BD. Negative urgency may help explain the association between lower white matter integrity of the cingulum and risk of SAs.