Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET

Abstract

Rationale: Among other monoamine neurotransmitters, dopamine is implicated in the pathophysiology of major depression. Experimental studies suggest the involvement of the mesolimbic dopamine system in the mechanism of action of antidepressant drugs. Previous in vivo imaging studies have studied striatal dopamine D2 receptor availability in depression but the results are equivocal thus far.

Objective: To study the striatal and thalamic dopamine D2 receptor availability in drug-naive patients with major depression was the aim of this study.

Materials and methods: Caudate, putamen, and thalamic dopamine D2 receptor availability was estimated using positron emission tomography and [11C]raclopride in 25 treatment-seeking drug-free patients (of whom 24 were drug-naive) with major depression (primary care patients) as well as in 19 demographically similar healthy control subjects. Receptor availability was expressed as the binding potential (BP ND), and analyses were carried out based on both regional and voxel-level BP ND estimates.

Results: No statistically significant differences in [11C]raclopride BP ND were observed between the groups either in the caudate nucleus (+1.7%, CI -4.8% to +8.3%), putamen (-1.0%, CI -7.2% to 5.1%), thalamus (-2.4%, CI -8.7% to 4.0%), or ventral striatum (-3.8%, CI -9.3% to +1.6%). In the patients, depressive symptoms were not associated with [11C]raclopride BP ND in any region.

Conclusions: The findings in this sample of treatment-seeking, drug-naive and predominantly first-episode patients with major depression do not support the involvement of striatal dopamine D2 receptors in the pathophysiology of the illness, but do not exclude the potential importance of dopaminergic mechanisms in antidepressant drug action.