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Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study.

ABSTRACT: Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure. METHODS:Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [11C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [11C]PBR28 distribution volume ratio (DVR). RESULTS:The total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm3: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=-0.72; p=0.006). CONCLUSIONS:These findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.

SUBMITTER: Selvaraj S

PROVIDER: S-EPMC6027955 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [<sup>11</sup>C]PBR28 study.

Selvaraj Sudhakar S Bloomfield Peter S PS Cao Bo B Veronese Mattia M Turkheimer Federico F Howes Oliver D OD

Schizophrenia research 20171012

Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure.<h4>Methods</h4>Fourteen patients with schizophrenia a ...[more]

PMID: 28893493

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Project description:ObjectiveThe study examined gray matter volume across psychosis diagnoses organized by dimensional and DSM-IV categories from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) sample.MethodIn total, 351 probands with psychosis (146 with schizophrenia, 90 with schizoaffective disorder, and 115 with psychotic bipolar I disorder), 369 of their first-degree relatives (134 were relatives of individuals with schizophrenia, 106 of individuals with schizoaffective disorder, and 129 of individuals with psychotic bipolar I disorder), and 200 healthy comparison subjects were assessed. Gray matter volumes from 3-T T1-weighted images were analyzed using the VBM8 toolbox for SPM8, and outcomes were determined at a false discovery rate-corrected threshold of p<0.005.ResultsAcross the psychosis dimension, probands (N=351) and relatives with psychosis spectrum disorders (N=34) showed substantial overlapping gray matter reductions throughout the neocortex, whereas relatives without psychosis spectrum (N=332) had normal gray matter volumes relative to comparison subjects. Across DSM-IV diagnoses, schizophrenia and schizoaffective probands showed overlapping gray matter reductions in numerous cortical and subcortical regions, whereas psychotic bipolar probands showed limited gray matter reductions localized to the frontotemporal cortex relative to comparison subjects. All relative groups had gray matter volumes that did not differ from comparison subjects.ConclusionsAcross the dimensional psychosis categories, these findings indicate extensive neocortical gray matter reductions in psychosis probands and relatives with psychosis spectrum disorders, possibly reflecting lifetime psychosis burden, but normal gray matter in nonpsychotic relatives. Traditional DSM-IV psychosis grouping revealed partially divergent gray matter phenotypes for probands with schizophrenia or schizoaffective disorder (extensive neocortical or subcortical gray matter reductions) relative to those with psychotic bipolar disorder (smaller reductions were limited to frontotemporal regions). The dimensional conceptualization of psychosis appears useful in defining more homogenous disease categories that may help identify underlying psychosis biomarkers and develop a biologically driven diagnostic system and targeted treatments.

Dataset Information

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study.

Publications

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [<sup>11</sup>C]PBR28 study.

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