Habenular functional connections are associated with depression state and modulated by ketamine

Background: Depression is a widespread mental health disorder with complex neurobiological underpinnings. The habenula, known as the 'anti-reward center', is thought to play a pivotal role in the pathophysiology of depression. This study aims to elucidate the association between the functional connections of the habenula and depression severity and to explore the modulation of these connections by ketamine. Methods: We studied 177 participants from a 7-T resting-state functional magnetic resonance imaging subset of the Human Connectome Project dataset to determine the associations between the functional connections of the habenula and depression. Additionally, we analyzed 60 depressed patients from our ketamine database to conduct a preliminary study on alterations in the functional connections of the habenula after ketamine infusions. We also investigated whether the baseline functional connectivity of the habenula is linked to subsequent improvement in depression. Results: We found that functional connections between the habenula and the substantia nigra, as well as the ventral tegmental area were negatively correlated with depression scores and elevated after ketamine infusions. Furthermore, the connection between the right habenula and the right substantia nigra was negatively associated with the improvement of depression. Limitations: The Human Connectome Project dataset primarily consists of data from healthy participants, with varying levels of depression scores. Conclusion: These results suggest that the habenula may facilitate depression by suppressing dopamine reward centers, and ketamine may relieve depression by disinhibiting these dopaminergic regions. This study may enhance our understanding of the neural underpinnings of depression and ketamine's antidepressant effects.