Antipsychotic dose and diminished neural modulation: a multi-site fMRI study |
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Authors: | Abbott C Juárez M White T Gollub R L Pearlson G D Bustillo J Lauriello J Ho B Bockholt H J Clark V P Magnotta V Calhoun V D |
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Institution: | a Dept. of Psychiatry, University of New Mexico, Albuquerque, New Mexico 87131, United Statesb The Mind Research Network, Albuquerque, New Mexico 87131, United Statesc Dept. of ECE, University of New Mexico, Albuquerque, New Mexico 87131, United Statesd Dept. of Psychology, University of New Mexico, Albuquerque, New Mexico 87131, United Statese Dept. of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, United Statesf Dept. of Radiology, University of Iowa, Iowa City, Iowa 52242, United Statesg Dept. of Psychiatry, University of Iowa, Iowa City, Iowa 52242, United Statesh Dept. of Psychiatry, Yale University School of Medicine, Hartford, Connecticut 06106, United Statesi Division of Child Psychiatry, University of Minnesota, Minneapolis, Minnesota 55454, United Statesj Olin Neuropsychiatry Research Center, Hartford, Connecticut 06106, United Statesk Department of Child Psychiatry, Erasmus MC, Sophia, Rotterdam, The Netherlandsl Depatment of Psychiatry, University of Missouri-Columbia, Columbia, Missouri 65212, United States |
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Abstract: | BackgroundThe effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.MethodsSeventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.ResultsGroup differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t77 = 2.01, P = 0.048).ConclusionThe results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia. |
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Keywords: | BOLD Blood Oxygen Level Dependent fMRI functional Magnetic Resonance Imaging MCIC Mind Clinical Imaging Consortium UNM University of New Mexico MGH Massachusetts General Hospital (Boston) IOWA Iowa Minn Minnesota CPZ Chlorpromazine SAPS Scale for the Assessment of Positive Symptoms SANS Scale for the Assessment of Negative Symptoms SOA Stimulus Onset Asynchrony EPI Echo-Planar Imaging GIFT Group Independent component analysis fMRI Toolbox ICA Independent Component Analysis PCA Principle Component Analysis SPM Statistical Parametric Mapping ANOVA Analysis of Variance WRAT3 Wide Range Achievement Test Third Edition |
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