Key players in major and bipolar depression--a retrospective analysis of in vivo imaging studies.

In the present study, we evaluated the contribution of the individual synaptic constituents of all assessed neurotransmitter systems by subjecting all available in vivo imaging studies on patients with unipolar major depressive disorder (MDD) and bipolar depression (BD) to a retrospective analysis. In acute MDD, findings revealed significant increases of prefrontal and frontal DA synthesis, decreases of thalamic and midbrain SERT, increases of insular SERT, decreases of midbrain 5-HT(1A) receptors and decreases of prefrontal, frontal, occipital and cingulate 5-HT(2A) receptors, whereas, in remission, decreases of striatal D₂ receptors, midbrain SERT, frontal, parietal, temporal, occipital and cingulate 5-HT(1A) receptors and parietal 5-HT(2A) receptors were observed. In BD, findings indicated a trend towards increased striatal D₂ receptors in depression and mania, decreased striatal DA synthesis in remission and decreased frontal D₁ receptors in all three conditions. Additionally, there is some evidence that ventrostriatal and hippocampal SERT may be decreased in depression, whereas in remission and mania elevations of thalamic and midbrain SERT, respectively, were observed. Moreover, in depression, limbic 5-HT(1A) receptors were elevated, whereas in mania a decrease of both cortical and limbic 5-HT(2A) receptor binding was observed. Furthermore, in depression, prefrontal, frontal, occipital and cingulate M2 receptor binding was found to be reduced. From this, a complex pattern of dysregulations within and between neurotransmitter systems may be derived, which is likely to be causally linked not only with the subtype and duration of disease but also with the predominance of individual symptoms and with the kind and duration of pharmacological treatment(s).