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

Abstract

The habenula (Hb) 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 (BD) and a history of suicide-related behaviors (SB+), 74 individuals with MDD or BD and a history of suicide ideation but no history of SB (SB−), and 75 healthy controls (HC). A seed-based approach was used to identify regions showing different rsFC with the Hb followed by ROI-to-ROI post-hoc comparisons. Compared to both SB− and HC, SB+ showed higher connectivity between the left Hb 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 Hb and left middle temporal gyrus, the left angular gyrus and the left posterior cingulate cortex as well as lower rsFC between the right Hb and the left thalamus, when compared to HC. These findings suggest that the Hb is involved in the neural circuitry of suicide. The higher habenular rsFC found in the SB+ may mediate a dysfunction in the mechanism that links the Hb with motor activity and contextual associative processing.

Classifying suicidal behavior with resting‐state functional connectivity and structural neuroimaging

“…However, our finding was more anterior to their temporal finding and so it is not directly comparable. We also identified increased RSFC between the left habenula and right parahippocampus, which we had identified in an overlapping sample of patients using a hypothesis‐based approach . Note that while this finding would not be replicated in the hold‐out sample if outliers were removed, this may be due to the smaller sample size and that these points are not true outliers (based on training data).…”

“…The habenular circuit has been implicated in depression . We created the habenula left and right ROIs manually in SPM8 (one individually placed voxel per side) according to previous publications from our lab . The locus coeruleus, dorsal raphe, median raphe, substantia nigra, and ventral tegmental area (VTA) are all a part of habenular circuitry , and they have been implicated in depression and in some cases suicidal behavior specifically .…”

Altered Static and Dynamic Functional Connectivity of Habenula Associated With Suicidal Ideation in First-Episode, Drug-Naïve Patients With Major Depressive Disorder

“…It is an important region that links the forebrain to midbrain, receiving inputs from the prefrontal cortex and basal ganglia regions and projecting directly or indirectly to target nuclei, particularly the dopaminergic ventral tegmental area (VTA), to regulate the monoaminergic system ( 12 , 13 ). Thus, it is associated with a range of behaviors related to cognitive and emotional processing, such as pain and stress responses, and is essential for reward systems and goal-directed behavior ( 14 ). Besides, the habenula was found to be activated by a no-reward-predicting target, which means that the habenula is also involved in the aversive antireward circuitry ( 15 ).…”

“…The activation of the habenula leads to the suppression of motor behavior by inhibiting the release of dopamine neurons when the individual is unable to obtain a reward or predicts a negative result ( 16 ). Given this nature, as a relay station between the basal ganglia and the limbic system, the habenula is not only involved in the motivation and emotional control of behavior but also plays a key role in behavioral responses induced by expected rewards ( 14 ).…”

“…To date, there is currently little research on the association between the habenula and suicide-related issues. A recent neuroimaging study of patients with mood disorders reported that both SB and SI was associated with abnormal connectivity of the habenula and the parahippocampal gyrus, amygdala ( 14 ). Besides MDD, changing neural connectivity of the habenula to locus coeruleus in past anorexia nervosa (pAN) with suicidality has also been discovered ( 19 ).…”