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Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

ABSTRACT: Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MRI) scans, and SAA assays were collected from 47 early course, stabilized outpatients with schizophrenia or schizoaffective disorder. Voxel-based morphometry analyses employing general linear models, adjusting for demographic and illness-related confounds, were used to investigate the associations between SAA, gray matter morphology, and neurocognitive impairment. SAA was related to working memory and executive function impairments. Higher SAA was significantly associated with lower gray matter density in broad regions of the frontal and medial-temporal lobes, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left DLPFC was found to significantly mediate the association between SAA and working memory impairment. Disease- and/or medication-related cholinergic dysfunction may be associated with brain volume abnormalities in early course schizophrenia, which may account for the association between SAA and cognitive dysfunction in the disorder.

SUBMITTER: Wojtalik JA

PROVIDER: S-EPMC3518587 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

Wojtalik Jessica A JA Eack Shaun M SM Pollock Bruce G BG Keshavan Matcheri S MS

Psychiatry research 20121115 2-3

Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MR ...[more]

PMID: 23158779

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Project description:Prior postmortem studies have shown gray matter (GM) microstructural abnormalities in schizophrenia. However, few studies to date have examined GM microstructural integrity in schizophrenia in vivo. Here, we employed diffusion kurtosis imaging (DKI) to test for differences in GM microstructure in eighteen schizophrenia (SZ) patients versus nineteen healthy controls (HC). GM microstructure was characterized in each participant using DKI-derived metrics of mean kurtosis (MK) and mean diffusivity (MD). Individual T1-weighted images were used to create subject-specific cortically-labelled regions of interest (ROIs) of the four cortical lobes and sixty-eight cortical GM regions delineated by the Desikan-Killiany atlas, and to derive the associated cortical thickness and area measures. The derived ROIs were also registered to the diffusion space of each subject and used to generate region-specific mean MK and MD values. We additionally administered the Wisconsin Card Sorting Test (WCST), Stroop test, and Trail Making Test part B (Trails-B) to test the relationship between GM metrics and executive function in SZ. We found significantly increased MK and MD in SZ compared to HC participants in the temporal lobe, sub-lobar temporal cortical regions (fusiform, inferior temporal, middle temporal and temporal pole), and posterior cingulate cortex after correcting for multiple comparisons. Correlational analyses revealed significant associations of MK and MD with executive function scores derived from the WCST, Stroop, and Trails-B tests, along with an inverse relationship between MK and MD and cortical thickness and area. A hierarchical multiple linear regression analysis showed that up to 85% of the inter-subject variability in cognitive function in schizophrenia measured by the WCST could be explained by MK in combination with either GM thickness or area. MK and MD appear to be sensitive to GM microstructural pathology in schizophrenia and may provide useful biomarkers of abnormal cortical microstructure in this disorder.

Dataset Information

Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

Publications

Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

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