Altered levels of dopamine transporter in the frontal pole and the striatum in mood disorders: A postmortem study

Abstract

Dopamine dysregulation is known to play a major role in the pathophysiology of major depressive disorders (MDD) and bipolar disorders (BD). The dopamine transporter (DAT) plays a critical role in regulating dopamine concentration at the synaptic cleft and therefore could have an important role in the molecular pathology of MDD and BD. To test this hypothesis, we measured levels of [³H]mazindol binding to DAT in Brodmann's area (BA) 10, BA 17 as well as in the dorsal and ventral striatum from 15 controls, 15 patients with MDD and 15 patients with BD, obtained postmortem, using in situ radioligand binding with autoradiography. Compared to controls, levels of [³H]mazindol binding to DAT was significantly higher in BA10 from patients with MDD but not BD. There was no significant difference in [³H]mazindol binding to DAT in BA 17 or the dorsal and ventral striatum from patients with MDD or BD. In addition, levels of [³H]mazindol binding show no correlation with donor age, postmortem interval, tissue pH, sex or duration of illness. In conclusion, our data suggest that changes in levels of DAT may be selectively affecting dopamine homeostasis in BA 10 in patients with MDD.

Keywords: Bipolar disorder; Dopamine transporter; Frontal pole; Major depression; Striatum.