Resting-State Functional Connectivity of the Habenula in Mood Disorder Patients With and Without Suicide-Related Behaviors

The habenula is a small midbrain structure that is important for brain signaling and learning from negative events. Thus, the habenula is strongly connected to both the reward system and motor regions. Increasing evidence suggests a role for the habenula in the etiology of psychiatric disorders, including mood and substance use disorders. However, no studies to date have investigated habenular resting-state functional connectivity (rsFC) in suicide-related behaviors (SB). The authors enrolled 123 individuals with major depressive disorder (MDD) or bipolar disorder and a history of suicide-related behaviors (SB+), 74 individuals with MDD or bipolar disorder and a history of suicidal ideation but no history of SB (SB–), and 75 healthy control subjects (HC). A seed-based approach was used to identify regions showing different rsFC with the habenula followed by region of interest to region of interest post hoc comparisons. Compared with both the SB– and HC groups, the SB+ group showed higher connectivity between the left habenula and the left parahippocampal gyrus, the right amygdala, and the right precentral and postcentral gyri. Patients with mood disorders displayed higher rsFC between the left habenula and left middle temporal gyrus, the left angular gyrus, and the left posterior cingulate cortex, as well as lower rsFC between the right habenula and the left thalamus, when compared with HCs. These findings suggest that the habenula is involved in the neural circuitry of suicide. The higher habenular rsFC found in the SB+ group may mediate a dysfunction in the mechanism that links the habenula with motor activity and contextual associative processing.