Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

Abstract

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.

Increased NigralSLC6A3Activity in Schizophrenia Patients: Findings From the Toronto–McLean Cohorts

“…The average SLC6A3 mRNA level in controls was only 0.37-fold of that in cases (P = .0034 by Student's t tests; figure 1E). Because it has been reported that haloperidol treatment reduced hDAT expression levels in SCZ patients, 33 our data suggest that significantly elevated SLC6A3 activity was associated with SCZ and was not a medication effect. Supporting this conclusion, neither antipsychotic medication dose (R 2 = .0052, P = .7899) nor years of medication exposure (R 2 = .048, P = .3979) was correlated with SLC6A3 mRNA levels, ruling out medication effects.…”

“…This possibility is consistent with a recent brain imaging finding that SCZ patients after 2 weeks of treatment with haloperidol displayed significantly reduced hDAT protein density compared with nontreated SCZ patients. 33 The T allele of rs1478435 may provide a protective effect by reducing hDAT expression levels to permit sufficient DA signaling. This interpretation is consistent with human genetic studies on the DA-catabolizing COMT gene that have reported reduced DA signaling in the prefrontal cortex in SCZ 49 and with imaging studies showing higher hDAT protein density in drug-naïve SCZ patients than in healthy controls.…”

“…55,56 The discrepancy with the protein findings reported here might be attributable to tissue dependence of protein expression or inhibitory effects of medication. 33…”

Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

“…Both effects are likely to have contributed to the reduction of radioligand binding to the DAT, which was observed after amphetamine challenge in animals and chronic amphetamine abusers. Moreover, decreases of striatal DAT binding have been observed after haloperidol in both schizophrenic patients (49) and healthy rats (28). Chronic treatment with neuroleptic compounds blocks neostriatal D 2 auto-and heteroreceptors, ultimately resulting in a reduction of neostriatal DA levels.…”

Small-Animal Single-Photon Emission Computed Tomographic Imaging of the Brain Serotoninergic Systems in Wild-Type and Mdrla Knockout Rats

“…In the field of neuropsychiatry, conventional SPECT has been used in humans to perform quantitative measurement of brain neuroreceptor availability in vivo, making this technique valuable for the study of neuropsychiatric disorders such as depression, 2 schizophrenia, 3 and feeding disorders. 4 However, despite this demonstrated potential in humans, the use of SPECT in combination with animal models of neuropsychiatric diseases has barely been investigated.…”