Four-modality imaging of unmedicated subjects with schizophrenia: 18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, and MRI.

Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.

Reading abilities and dopamine D2/D3 receptor availability: An inverted U-shaped association in subjects with schizophrenia.

Reading impairments are prominent trait-like features of cognitive deficits in schizophrenia, predictive of overall cognitive functioning and presumably linked to dopaminergic abnormalities. To evaluate this, we used 18F-fallypride PET in 19 healthy and 21 antipsychotic-naïve schizophrenia subjects and correlated dopamine receptor binding potentials in relevant AFNI-derived regions and voxelwise with group performance on WRAT4 single-word reading subtest. Healthy subjects' scores were positively and linearly associated with D2/D3 receptor availability in the rectus, orbital and superior frontal gyri, fusiform and middle temporal gyri, as well as middle occipital gyrus and precuneus, all predominantly in the left hemisphere and previously implicated in reading, hence suggesting that higher dopamine receptor density is cognitively advantageous. This relationship was weakened in schizophrenia subjects and in contrast to healthy participants followed an inverted U-shaped curve both in the cortex and dorsal striatum, indicating restricted optimal range of dopamine D2/D3 receptor availability for cognitive performance in schizophrenia.

Relationship between white matter glucose metabolism and fractional anisotropy in healthy and schizophrenia subjects.

Decreased fractional anisotropy and increased glucose utilization in the white matter have been reported in schizophrenia. These findings may be indicative of an inverse relationship between these measures of white matter integrity and metabolism. We used 18F-fluorodeoxyglucose positron emission tomography and diffusion-tensor imaging in 19 healthy and 25 schizophrenia subjects to assess and compare coterritorial correlation patterns between glucose utilization and fractional anisotropy on a voxel-by-voxel basis and across a range of automatically placed representative white matter regions of interest. We found a pattern of predominantly negative correlations between white matter metabolism and fractional anisotropy in both healthy and schizophrenia subjects. The overall strength of the relationship was attenuated in subjects with schizophrenia, who displayed significantly fewer and weaker correlations in all regions assessed with the exception of the corpus callosum. This attenuation was most prominent in the left prefrontal white matter and this region also best predicted the diagnosis of schizophrenia. There exists an inverse relationship between the measures of white matter integrity and metabolism, which may therefore be physiologically linked. In subjects with schizophrenia, hypermetabolism in the white matter may be a function of lower white matter integrity, with lower efficiency and increased energetic cost of task-related computations.

Positive association between cerebral grey matter metabolism and dopamine D2/D3 receptor availability in healthy and schizophrenia subjects: An 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography study.

Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.Results:18F-fluorodeoxyglucose uptake and 18F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.

Dopamine receptor density and white mater integrity: 18F-fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects.

Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and 18F-fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D2/D3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch's t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and 18F-fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between 18F-fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D2/D3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.

Addiction Disorder Considerations for Patients Seeking Psychotherapy.

Substance use disorders are widespread and cause significant dysfunction. Substance use disorders often co-occur with other psychiatric disorders. Because of this overlap, clinicians commonly encounter patients at risk for substance abuse disorders. This article reviews strategies to aid the practicing clinician in the screening, assessment, intervention, and referral of their parents at risk for substance use disorders.

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.