Structural connectivity of dopaminergic pathways in major depressive disorder

Accumulating evidence points to imbalanced dopamine (DA) signaling and circulating levels in the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented a thorough examination of DA neural pathways in MDD. We uniquely employed ultra-high field diffusion MRI at 7.0 Tesla to map the white matter architecture and integrity of several DA pathways in MDD patients. Fifty-three MDD patients and 12 healthy controls (HCs) were enrolled in the final analysis. Images were acquired using a 7.0 Tesla MRI scanner. FreeSurfer was used to segment components of DA pathways, and MRtrix was used to perform preprocessing and tractography of mesolimbic, mesocortical, nigrostriatal, and unconventional DA pathways. Bayesian analyses assessed the impact of MDD and clinical features on DA tracts. MDD was associated with perturbed white matter microstructural properties of the nigrostriatal pathway, while several MDD features (severity of depression/age of onset/insomnia) related to connectivity changes within mesocortical, nigrostriatal, and unconventional pathways. MDD is associated with microstructural differences in the nigrostriatal pathway. The findings provide insight into the structural architecture and integrity of several DA pathways in MDD, and implicate their involvement in the clinical manifestation of MDD.