Major depressive disorder is associated with reduced intrinsic connectivity between the bed nucleus of the stria terminalis and ventral striatum

Background: The bed nucleus of the stria terminalis (BNST) plays a critical role in the neural processing of negative emotions. To date, no studies have investigated whether intrinsic connectivity of the BNST is associated with major depressive disorder (MDD) or with the severity of clinical symptoms in individuals with depression. Methods: Resting-state functional magnetic resonance imaging (fMRI, 7 Tesla (7T)) with seed-to-voxel-analysis was used to compare the intrinsic connectivity of the BNST between individuals with MDD (N=17) and healthy volunteers (N=29). Exploratory analyses were also conducted to determine whether intrinsic connectivity of the BNST was associated with the severity of clinical mood or anxiety symptoms in individuals with MDD, as assessed via scores on the clinician-administered Hamilton Anxiety Rating Scale (HAM-A) and the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Compared to healthy volunteers, individuals with MDD exhibited reduced intrinsic connectivity between the BNST and regions of the right ventral striatum. No significant associations were noted between intrinsic connectivity and the severity of anxious or depressive symptoms in MDD participants. Limitations: The small sample size makes it difficult to assess whether clinical heterogeneity impacted these findings. Future studies that combine experimental paradigms with neuroimaging are needed to shed light on the functional implications of these results. Conclusions: Reduced intrinsic connectivity between the BNST and striatum may reflect altered activity in the neural circuits responsible for stress and reward processing. These findings can be used to guide future work investigating risk factors for MDD and provide potential targets for clinical intervention.