Acute anxiety disorder, major depressive disorder, bipolar disorder and schizophrenia are related to different patterns of nigrostriatal and mesolimbic dopamine dysfunction

Abstract

Abstract Dopamine (DA) receptor and transporter dysfunctions play a major role in the pathophysiology of neuropsychiatric diseases including anxiety disorder (AD), major depressive disorder (MDD), bipolar disorder (BD) in the manic (BDman) or depressive (BDdep) state and schizophrenia (SZ). We performed a PUBMED search, which provided a total of 239 in vivo imaging studies with either positron emission tomography (PET) or single-proton emission computed tomography (SPECT). In these studies, DA transporter binding, D1 receptor (R) binding, D2R binding, DA synthesis and/or DA release in patients with the primary diagnosis of acute AD (n=310), MDD (n=754), BDman (n=15), BDdep (n=49) or SZ (n=1532) were compared to healthy individuals. A retrospective analysis revealed that AD, MDD, BDman, BDdep and SZ differed as to affected brain region(s), affected synaptic constituent(s) and extent as well as direction of dysfunction in terms of either sensitization or desensitization of transporter and/or receptor binding sites. In contrast to AD and SZ, in MDD, BDman and BDdep, neostriatal DA function was normal, whereas MDD, BDman, and BDdep were characterized by the increased availability of prefrontal and frontal DA. In contrast to AD, MDD, BDman and BDdep, DA function in SZ was impaired throughout the nigrostriatal and mesolimbocortical system with an increased availability of DA in the striatothalamocortical and a decreased availability in the mesolimbocortical pathway.