No 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.

Objective: To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D₂ receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). Background: FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. Methods: 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). Results: In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. Conclusion: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.

Disturbances of dopamine (DA), serotonin (5-HT) and/or norepinephrine (NE) functions are implied in attention-deficit hyperactivity disorder (ADHD). However, the precise cortical and subcortical mechanisms are still not fully understood. In the present survey, we conducted a PUBMED search, which provided 37 in vivo investigations with PET and SPECT on 419 ADHD patients and 490 controls. The retrospective analysis revealed increased striatal DA transporter (DAT) in adolescent as well as adult medication-naïve and not acutely medicated patients. In acutely medicated adults, DAT was not different from controls. Midbrain DAT was normal in adults, but decreased in adolescents. Striatal D2 receptor (R) binding was normal in both adolescents (not acutely medicated) and adults (acutely medicated and not acutely medicated). In medication-naïve adults, DA synthesis was decreased in putamen and amygdala, but normal in the whole striatum and midbrain. In not acutely medicated adults, DA synthesis was reduced in putamen, whole striatum, prefrontal cortex, frontal cortex, amygdala and midbrain, whereas, in adolescents, no regional differences were observed. In adult (not acutely medicated) subjects, cingulate D1R was reduced. 5-HT transporter (SERT) binding was decreased in striatum and thalamus, but normal in midbrain, neocortex and limbic regions, whereas, in medication-naïve adults, SERT was diminished in striatum and midbrain, but normal in thalamus and neocortex. The findings suggest transient stages of synaptic DA shortage as well as DA surplus in individual brain regions, which elicit presynaptic as well as postsynaptic compensatory mechanisms, striving to attain functional homeostasis. Thereby, it remains a matter of debate, whether ADHD may be characterized by a general hypo- or hyperactivity of DA and/or 5-HT function.