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-HT1A receptors and decreases of prefrontal, frontal, occipital and cingulate 5-HT2A receptors, whereas, in remission, decreases of striatal D2 receptors, midbrain SERT, frontal, parietal, temporal, occipital and cingulate 5-HT1A receptors and parietal 5-HT2A 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-HT1A receptors were elevated, whereas in mania a decrease of both cortical and limbic 5-HT2A 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).

► All in vivo imaging studies on MDD and BD were retrospectively analyzed.
► In MDD, a decrease of midbrain 5-HT may be inferred.
► In addition, cortical and cingulate 5-HT appear to be increased.
► In BD, findings suggest an increase of midbrain and limbic 5-HT.
► In mania, an elevation of cortical and limbic 5-HT may be inferred.
► Remission may be associated with a normalization of cortical and cingulate 5-HT.