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

Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-fallypride positron emission tomography was performed on 20 medication-naïve and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications

Neurobiology and phenotypic expression in early onset schizophrenia

AIM: Early-onset schizophrenia (onset before adulthood) is a rare and severe form of the disorder that shows phenotypic and neurobiological continuity with adult-onset schizophrenia. Here, we provide a synthesis of keynote findings in this enriched population to understand better the neurobiology and pathophysiology of early-onset schizophrenia. METHODS: A synthetic and integrative approach is applied to review studies stemming from epidemiology, phenomenology, cognition, genetics and neuroimaging data. We provide conclusions and future directions of research on early-onset schizophrenia. RESULTS: Childhood and adolescent-onset schizophrenia is associated with severe clinical course, greater rates of premorbid abnormalities, poor psychosocial functioning and increased severity of brain abnormalities. Early-onset cases show similar neurobiological correlates and phenotypic deficits to adult-onset schizophrenia, but show worse long-term psychopathological outcome. Emerging technological advances have provided important insights into the genomic architecture of early-onset schizophrenia, suggesting that some genetic variations may occur more frequently and at a higher rate in young-onset than adult-onset cases. CONCLUSIONS: Clinical, cognitive, genetic and imaging data suggest increased severity in early-onset schizophrenia. Studying younger-onset cases can provide useful insights into the neurobiological mechanisms of schizophrenia and the complexity of gene-environment interactions leading to the emergence of this debilitating disorder

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

Background: Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine D2/D3 dopamine correlates with frontal cortical related cognitive task performance in schizophrenia. Methods: Resting-state 18F-fallypride positron emission tomography was performed on 20 medication-naïve and 5 previously medicated (for brief earlier periods) patients with schizophrenia and 19 age- and sex-matched normal controls. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Results: Images of the voxel-by-voxel correlation coefficient between Fallypride binding and WCST and CVLT performance showed predominantly negative correlations in patients in contrast to positive correlations in healthy volunteers. This was especially marked for the temporal lobe, Brodmann areas 46 and 47, striatum, and thalamus. Examination of the distribution of correlation coefficients between neuropsychological scores and binding potential in regions of interest showed healthy volunteer correlations significantly more positive correlations with a more positive skewed distribution. Patients with schizophrenia had a negative skew to the distribution. Permutation analysis is used to confirm correlation differences, addressing the issue of regional intercorrelations. Conclusions: The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance and consistent with previous studies that failed to find cognitive improvement with typical dopamine-blocking medications. Our findings in this study reinforce the concept of distributed influence of dopamine on performance involving both striatal and extrastriatal regions. These influences are trait-like in nature extending across cognitive tasks in healthy subjects. Patients with schizophrenia show relationships between performance and binding potential that are anomalous and likely heterogeneous, leaving a disturbed distribution of regional binding potential versus performance correlations. Our findings are also consistent with the widely interconnected network patterns observed in fMRI connectivity studies rather than with a restricted network of several small, localized, and specialized neural loci

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

Background: Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine D2/D3 dopamine correlates with frontal cortical related cognitive task performance in schizophrenia. Methods: Resting-state 18F-fallypride positron emission tomography was performed on 20 medication-naïve and 5 previously medicated (for brief earlier periods) patients with schizophrenia and 19 age- and sex-matched normal controls. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Results: Images of the voxel-by-voxel correlation coefficient between Fallypride binding and WCST and CVLT performance showed predominantly negative correlations in patients in contrast to positive correlations in healthy volunteers. This was especially marked for the temporal lobe, Brodmann areas 46 and 47, striatum, and thalamus. Examination of the distribution of correlation coefficients between neuropsychological scores and binding potential in regions of interest showed healthy volunteer correlations significantly more positive correlations with a more positive skewed distribution. Patients with schizophrenia had a negative skew to the distribution. Permutation analysis is used to confirm correlation differences, addressing the issue of regional intercorrelations. Conclusions: The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance and consistent with previous studies that failed to find cognitive improvement with typical dopamine-blocking medications. Our findings in this study reinforce the concept of distributed influence of dopamine on performance involving both striatal and extrastriatal regions. These influences are trait-like in nature extending across cognitive tasks in healthy subjects. Patients with schizophrenia show relationships between performance and binding potential that are anomalous and likely heterogeneous, leaving a disturbed distribution of regional binding potential versus performance correlations. Our findings are also consistent with the widely interconnected network patterns observed in fMRI connectivity studies rather than with a restricted network of several small, localized, and specialized neural loci