Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies

Background: Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies. Methods: Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted. Results: We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D-2/3 receptor availability (g = 0.06, p = 0.620), or combined dopamine synthesis and release capacity (g = 0.19, p = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers (g = -0.56, p = 0.006), but not when tracers with an affinity for serotonin transporters were included (g= -0.21, p = 0.420). Subgroup analysis showed greater dopamine release (g = 0.49, p = 0.030), but no difference in dopamine synthesis capacity (g = -0.21, p = 0.434) in the MDD group. Striatal D-1 receptor availability was lower in patients with MDD in two studies. Conclusions: The meta-analysis indicates striatal DAT availability is lower, but D-2/3 receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D-1 receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.

Automated summary

Background: Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies. Methods: Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted. Results: We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D-2/3 receptor availability (g = 0.06, p = 0.620), or combined dopamine synthesis and release capacity (g = 0.19, p = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers (g = -0.56, p = 0.006), but not when tracers with an affinity for serotonin transporters were included (g= -0.21, p = 0.420). Subgroup analysis showed greater dopamine release (g = 0.49, p = 0.030), but no difference in dopamine synthesis capacity (g = -0.21, p = 0.434) in the MDD group. Striatal D-1 receptor availability was lower in patients with MDD in two studies. Conclusions: The meta-analysis indicates striatal DAT availability is lower, but D-2/3 receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D-1 receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.