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Crum W.R.,Center for Neuroimaging science | Lerch J.P.,University of Toronto | Modo M.,Kings College London | Cooper J.D.,Kings College London | Williams S.C.R.,Center for Neuroimaging science
Biological Psychiatry | Year: 2014

Background Increasing evidence suggests that antipsychotic drugs (APD) might affect brain structure directly, particularly the cerebral cortex. However, the precise anatomical loci of these effects and their underlying cellular basis remain unclear. Methods With ex vivo magnetic resonance imaging in rats treated chronically with APDs, we used automated analysis techniques to map the regions that show maximal impact of chronic (8 weeks) treatment with either haloperidol or olanzapine on the rat cortex. Guided by these imaging findings, we undertook a focused postmortem investigation with stereology. Results We identified decreases in the volume and thickness of the anterior cingulate cortex (ACC) after chronic APD treatment, regardless of the APD administered. Postmortem analysis confirmed these volumetric findings and demonstrated that chronic APD treatment had no effect on the total number of neurons or S100β+ astrocytes in the ACC. In contrast, an increase in the density of these cells was observed. Conclusions This study demonstrates region-specific structural effects of chronic APD treatment on the rat cortex, primarily but not exclusively localized to the ACC. At least in the rat, these changes are not due to a loss of either neurons or astrocytes and are likely to reflect a loss of neuropil. Although caution needs to be exerted when extrapolating results from animals to patients, this study highlights the power of this approach to link magnetic resonance imaging findings to their histopathological origins. © 2014 Society of Biological Psychiatry.

Perez-Iglesias R.,Marques Of Valdecilla University Hospital | Perez-Iglesias R.,Center for Neuroimaging science | Perez-Iglesias R.,Kings College London | Perez-Iglesias R.,Cibersam Research Center Biomedica En Red En El Area Of Salud Mental | And 40 more authors.
American Journal of Psychiatry | Year: 2010

Objective: Impaired cognitive function has been identified as a core feature of schizophrenia. However, a significant proportion of patients do not show any cognitive deficits. The aim of this study was to assess if there were differences in white matter integrity between patients with and without cognitive impairment. Method: A diffusion tensor imaging study and neurocognitive assessment were conducted in 49 patients with firstepisode psychosis and 41 healthy comparison subjects. Subjects were assessed using the Continuous Performance Test, the Grooved Pegboard Test, the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B. For each test, the patient sample was subdivided according to performance, with those scoring more than one standard deviation below the normative mean categorized as impaired. For each cognitive domain, white matter fractional anisotropy in deficit and nondeficit subgroups was compared using a voxel-based analysis. A nonparametric statistical method, controlling for multiple comparisons, was applied. Results: Impairment on the Trail Making Test Part B was associated with reduced fractional anisotropy in the right/left anterior thalamic radiation and inferior frontooccipital fasciculus, forceps minor, and left superior and inferior longitudinal fasciculi. Patients exhibiting Grooved Pegboard Test impairment showed reduced fractional anisotropy in the forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal and corticopontine tracts. Impaired performance on the Rey Auditory Verbal Learning Test and Continuous Performance Test was not associated with significant differences in fractional anisotropy. Conclusions: deficits in executive and motor functioning in patients with firstepisode psychosis are associated with reductions in white matter integrity in the major fasciculi that connect the frontal and temporal cortices as well as in pathways connecting cortical and subcortical regions. Their presence at the onset of illness, in minimally medicated patients, indicates that these findings are not attributable to effects of chronic illness or its treatment.

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