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

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.

Bipolar Disorder and Parkinson's Disease: A 123I-Ioflupane Dopamine Transporter SPECT Study

“…Apart from dopaminergic dysfunction, which can manifest with different patterns in the nigrostriatal and mesolimbocortical pathways in BD (33) and PD, the two disorders might potentially share the involvement of additional pathophysiological processes. Impairment in the serotoninergic and glutamatergic circuitries has been classically described in BD disorder (34) and is involved in certain motor and non-motor symptoms of PD such as tremor (35) and mood dysfunction (36).…”

Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study

“…According to the monoamine hypothesis, monoamine neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE), have always been the key aspects in mood disorders. Although previous genetic, biological and pharmacological studies confirmed the important role of 5-HT in MDD (7,9), accumulating evidence suggested the contribution of dysregulated DA and NE transmission on both MDD and BD (10)(11)(12). DA and NE play an important role not only in cognitive function, but also in emotion regulation (13,14).…”

MK-801-induced behavioral and dopaminergic responses in the shell part of the nucleus accumbens in adult rats are disrupted after neonatal blockade of the ventral subiculum

“…The hypothesis of a striatal hyperdopaminergy is reinforced by data that show that antipsychotics all exhibit the property to block DAergic D2 receptors to some degree (Kaar et al, 2020). As regards striatal hyperdopaminergic activity, meta-analyses of brain imaging studies suggest an increase in DA release in either both the dorsal and ventral parts of the striatum (Nikolaus et al, 2019) or only in the dorsal striatum (mainly in the associative striatum)(McCutcheon et al, 2018). However, subdivisions of the ventral striatum and differential changes in these sub-territories have never be reported in such meta-analyses, whereas preclinical studies support the view that the shell subdivision of the nucleus accumbens (Nacc), part of the ventral striatum, is the shared anatomical target for all antipsychotics (typical and atypical antipsychotics), with the dorsolateral striatum being the preferential target for typical antipsychotics (Deutch et al, 1992, Merchant and Dorsa, 1993, Mo et al, 2005; Jennings et al, 2006; Natesan et al, 2006; Collins et al, 2014).…”