Brain Volume Changes After Withdrawal of Atypical Antipsychotics in Patients With First-Episode Schizophrenia

Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
Journal of clinical psychopharmacology (Impact Factor: 3.24). 02/2011; 31(2):146-53. DOI: 10.1097/JCP.0b013e31820e3f58
Source: PubMed


The influence of antipsychotic medication on brain morphology in schizophrenia may confound interpretation of brain changes over time. We aimed to assess the effect of discontinuation of atypical antipsychotic medication on change in brain volume in patients. Sixteen remitted, stable patients with first-episode schizophrenia, schizoaffective or schizophreniform disorder and 20 healthy controls were included. Two magnetic resonance imaging brain scans were obtained from all subjects with a 1-year interval. The patients either discontinued (n = 8) their atypical antipsychotic medication (olanzapine, risperidone, or quetiapine) or did not (n = 8) discontinue during the follow-up period. Intracranial volume and volumes of total brain, cerebral gray and white matter, cerebellum, third and lateral ventricle, nucleus caudatus, nucleus accumbens, and putamen were obtained. Multiple linear regression analyses were used to assess main effects for group (patient-control) and discontinuation (yes-no) for brain volume (change) while correcting for age, sex, and intracranial volume. Decrease in cerebral gray matter and caudate nucleus volume over time was significantly more pronounced in patients relative to controls. Our data suggest decreases in the nucleus accumbens and putamen volumes during the interval in patients who discontinued antipsychotic medication, whereas increases were found in patients who continued their antipsychotics. We confirmed earlier findings of excessive gray matter volume decrements in patients with schizophrenia compared with normal controls. We found evidence suggestive of decreasing volumes of the putamen and nucleus accumbens over time after discontinuation of medication. This might suggest that discontinuation reverses effects of atypical medication.

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    • "Speculatively, these changes in the morphology of Iba1 + microglia may therefore be linked to potential loss of neuropil in the ACC and S2 cortices, leading to a volume decrease. This hypothesis is consistent with recent evidence that microglia are critical mediators of activity-dependent synaptic remodelling and plasticity in the healthy brain (Boonstra et al., 2011; Cazorla et al., 2014; Kettenmann et al., 2013; Wake et al., 2009; Zatorre et al., 2012). In contrast, increases in "
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    • "We also indicate which of the findings pass the more conservative Bonferroni multiple comparison-corrected threshold of p o0.00625 (two-tailed). Based on evidence for the effects of antipsychotic medication on basal ganglia volumes (Gur et al., 1998; Hulshoff Pol and Kahn, 2008; Boonstra et al., 2011; Li et al., 2011), we examined the effect of current antipsychotic medication type (typical/atypical) and dose (chlorpromazine-equivalent dose) on basal ganglia volumes, using mixed model regression and correlation analysis, respectively. Cohen's d weighted mean effect sizes based on each of the seven single site samples and also based on the full sample were computed. "
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