Defending is a Balancing Act: The Consequences of Defending Victims of Bullying Depend on Defender's Popularity and Social Preference.

Bipolar disorder is a chronic, severe psychiatric condition that affects approximately 2% of the global population []. The disorder involves recurring episodes of mania, typically associated with elevated dopaminergic activity; and episodes of depression, associated with reduced dopaminergic activity []. Parallel dysregulation of serotonergic activity appears to contribute to affective instability and exacerbation of depressive symptoms []. These imbalances in monoaminergic neurotransmission may impair functional coordination between limbic and cortical regions, thereby destabilizing emotion-regulation circuits [–]. Studies of the habenula in depression imply its involvement in bipolar disorder. The habenula regulates monoaminergic neurotransmission [] by receiving afferent input from regions such as the prefrontal cortex, amygdala and nucleus accumbens, and sending efferent projections to the raphe nuclei and ventral tegmental area [, ]. Reduced habenular volume in individuals with depression correlates with severity of their anhedonia [, ], and neuromodulation that sends major depressive disorder into remission increases gray matter volume in the habenula []. Depression appears to involve aberrant functional connectivity between the habenula and limbic/sensorimotor networks, which may impair emotional regulation and sensory integration [–]. The demonstrated role of the habenula in mood dysregulation in major depressive disorder implies that it may contribute to similar dysregulation in bipolar disorder. To examine this question, we compared the volume and functional connectivity of the habenula between individuals with bipolar disorder and controls, and further assessed their associations with clinical symptom severity. To begin to identify molecular pathways that may explain disorder-associated alterations, we integrated our structural and functional findings with pathway-related polygenic risk scores and transcriptomic profiles in habenula. Elucidating how changes in gene expression contribute to bipolar disorder is critical given that its heritability lies between 70% and 90% and 10–15% of first-degree relatives of affected individuals develop mood disorders [, ].