D2/D3 dopamine receptor binding with [F-18]fallypride correlates of executive function in medication-naïve 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...

Examination and Comparison of Cognitive and Executive Functions in Clinically Stable Schizophrenia Disorder, Bipolar Disorder, and Major Depressive Disorder

“…Poor performance in patients with SC is associated with poor cognitive flexibility, problem solving, and attention control in the Wisconsin Card Sorting Task. Executive dysfunction predicts poor performance in patients, failure in therapeutic interventions, and limited rehabilitation [ 10 ]. One of the important questions raised in the field of SC is whether the neuropsychological deficits in SC are more severe than other disorders such as bipolar disorder and major depressive disorder.…”

No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

“…Previous studies have reported associations between D2-R availability and cognition that differ between patients with schizophrenia and HC. In some cases, significant correlations have been reported in one group but not the other 20,21 , and in other cases, the direction of the relationship has been reversed between groups 19,21 . The idea of an altered impact of dopamine on cognitive function in schizophrenia motivated us to explore an interaction effect of FEP/HC status on the relationship between cognitive functioning and D2-R availability.…”

“…Given the role of D2-R in cognition, surprisingly few studies have investigated the relationship between D2-R availability and cognition in extrastriatal regions. Four studies have so far investigated this relationship in patients with schizophrenia revealing no clear pattern of associations [19][20][21][22] . Moreover, the observed correlations in these studies differ from those observed in HC; either showing associations in the opposite direction or a lack of a significant relationship [23][24][25][26] (see Supplementary Table 1).…”

Neural Correlates of Autobiographical Memory: Evidence From a Positron Emission Tomography Study in Patients With Mild Cognitive Impairment and Alzheimer's Disease

“…For analyses of the Brodmann areas, the gyri, hippocampus, insula, and subcortical structures, the FDG uptake values were obtained using AFNI regions of interest ( 25 ). Details on the quality and reliability of the co-registration procedure are described in another dataset in Vyas et al ( 26 ).…”