Structural-functional decoupling predicts suicide attempts in bipolar disorder patients with a current major depressive episode

Bipolar disorder (BD) is associated with a high risk of suicidality, and it is challenging to predict suicide attempts in clinical practice to date. Although structural and functional connectivity alterations from neuroimaging studies have been previously reported in BD with suicide attempts, little is known about how abnormal structural and functional connectivity relates to each other. Here, we hypothesize that structure connectivity constrains functional connectivity, and structural-functional coupling is a more sensitive biomarker to detect subtle brain abnormalities than any single modality in BD patients with a current major depressive episode who had attempted suicide. By investigating structural and resting-state fMRI connectivity, as well as their coupling among 191 BD depression patients with or without a history of suicide attempts and 113 healthy controls, we found that suicide attempters in BD depression patients showed significantly decreased central-temporal structural connectivity, increased frontal-temporal functional connectivity, along with decreased structural-functional coupling compared with non-suicide attempters. Crucially, the altered structural connectivity network predicted the abnormal functional connectivity network profile, and the structural-functional coupling was significantly correlated with suicide risk but not with depression or anxiety severity. Our findings suggest that the structural connectome is the key determinant of brain dysfunction, and structural-functional coupling could serve as a valuable trait-like biomarker for BD suicidal predication over and above the intramodality network connectivity. Such a measure can have clinical implications for early identification of suicide attempters with BD depression and inform strategies for prevention.