Dopaminergic frontostriatal pathways in major depressive disorder and childhood sexual abuse: a multimodal neuroimaging investigation

Dysregulated dopaminergic signaling has been implicated in the pathophysiology of major depressive disorder (MDD) and childhood sexual abuse (CSA), but inconsistencies abound. In a multimodal PET-functional MRI study, harnessing the highly selective tracer [¹¹C]altropane, we investigated dopamine transporter availability (DAT) and resting-state functional connectivity (rsFC) within reward-related regions among 112 unmedicated individuals (MDD: n = 37, MDD/CSA: n = 18; CSA no MDD: n = 14; controls: n = 43). Striatal DAT and seed-based rsFC were assessed in the dorsal and ventral striatum and the ventral tegmental area. We found that MDD, CSA, and their co-occurrence were associated with region-specific DAT abnormalities, which were related to the number of lifetime MDD episodes and the duration of childhood maltreatment. CSA was further associated with lower frontostriatal rsFC. The findings provide compelling evidence of DA dysregulation in MDD and CSA, and highlight potential prevention and treatment targets.