79. D2/D3 Dopamine Receptor Binding With [F-18] Fallypride Correlates of Executive Function in Medication-Naive Patients With Schizophrenia

Abstract

individuals at clinical high risk (CHR) for developing schizophrenia is not well characterized. Methods: We studied youth (ages 11-30) meeting CHR for psychosis criteria (n = 30), individuals early in their schizophrenia illness (ESZ; n = 22), and healthy adolescents and young adults (HC; n = 72). Functional magnetic resonance imaging was collected during Go/NoGo response inhibition task performance. Voxelwise main effects of Group (p<.001 height threshold, family-wise error corrected P < .05) for incorrect NoGo versus correct Go activations were examined, and correlated with the signal detection measure d'. Results: Error rates and error-related activations in anterior cingulate and dorsolateral prefrontal cortex were equivalent across the three groups. A significant main effect of Group for the contrast of NoGo errors relative to correct Go responses was detected in the left cerebellum. This main effect of Group was explained by the ESZ group showing significantly less errorrelated activation, relative to the HC group (with the CHR group differing from neither). In HC individuals, higher error-related contrast values in this cerebellar region significantly related to better d', a relationship that was not present in either of the clinical groups (group slopes difference, P < .05). Conclusion: ESZ patients showed significantly less cerebellar activation during error processing, relative to HC participants. In HCs, cerebellar activation in this region was significantly related to better signal detection. A role for the cerebellum in performance monitoring is increasingly recognized, and these data suggest that the normal relationship between cerebellar error-related responses and task performance breaks down in both CHR and ESZ groups. Background: Schizophrenia has been associated with thalamic hyperconnectivity with sensory regions, including the middle and superior temporal gyrus, and hypoconnectivity with cerebellar and prefrontal regions. While thalamic dysconnectivity has been consistently replicated in chronic schizophrenia samples, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. Methods: Resting-state fMRI data were collected from clinical high-risk youth (n = 45; CHR), early illness schizophrenia (n = 74; ESZ) patients, and healthy controls (n = 85; HC). Age-adjusted whole-brain functional connectivity, seeded from the thalamus, was compared among the three groups. Main effects of group (FDR-corrected, p = .01) were followed up with Tukey-corrected pairwise comparisons. Results: Significant main effects of group were observed in 8 regions: 2 left middle temporal regions, 2 right middle temporal regions, a left superior temporal region, a right superior temporal region, a left cerebellar region, and a bilateral thalamic region. Pairwise follow-up tests (P < .05) conducted on extracted mean connectivity values revealed that, consistent with data comparing chronic schizophrenia patients to HCs, ESZ patients demonstrated greater thalam...

In Silico Study of Metoclopramide as A Small Molecule of Dopamine D2 Receptor: a Quantum-Mechanical (QM) Based Molecular Docking Treatment

“…In recent years, antagonist drugs have shown better properties than agonist compounds for binding with dopamine D2 receptor. The main antagonist drugs are atypical antipsychotics [26], cinnarizine [27], chloroethylnorapomorphine [28], desmethoxyfallypride [29], domperidone [30], metoclopramide [31], eticlopride [32], fallypride [33], hydroxyzine [34] and itopride [35].…”