Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment

University of North Carolina at Chapel Hill, Department of Psychiatry, Chapel Hill, NC 27510-7160, USA.
Psychiatry Research (Impact Factor: 2.47). 01/2007; 148(2-3):121-32. DOI: 10.1016/j.pscychresns.2006.04.008
Source: PubMed


The purpose of this pilot study was to: (1) determine if regional brain volume change occurs in schizophrenia patients during very short periods of withdrawal from, or stable treatment with, antipsychotics, and; (2) compare results of region-of-interest (ROI) to voxel-based morphometry (VBM) methods. In two small groups of schizophrenic inpatients, magnetic resonance imaging was performed before and after antipsychotic withdrawal, and at two time points during stable chronic antipsychotic treatment. Regional brain volumes were measured using ROI methods. Grey matter volume was measured with VBM. The medication withdrawal group showed no effect of treatment state or antipsychotic type on regional brain volumes with ROI analysis, but effects of both treatment state and antipsychotic type on grey matter volume were observed with VBM in right middle frontal, right medial frontal, right and left superior frontal, right cingulate, and right superior temporal gyrii as well as in the right and left hippocampal gyrii. The chronic stable treatment group showed an effect of time on right caudate, left hippocampal, and total cerebrospinal fluid volumes with ROI analysis, while effects of both time and antipsychotic type were observed with VBM on grey matter volume in the left superior temporal lobe. No findings survived correction for multiple comparisons. A positive correlation between regional volume change and emerging psychopathology was demonstrated using ROI methods in the medication withdrawal group. Treatment state and emergent symptoms in schizophrenia patients were associated with regional volume change over very short time periods. Longitudinal regional brain volume change in schizophrenia patients is likely physiologic and therefore potentially reversible.

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    • "In original studies, antipsychotic medication exposure has been associated with, for example, decreases in frontal, temporal and parietal gray matter (Ho et al., 2011), hippocampal volume (Ebdrup et al., 2011; Mamah et al., 2012) and thalamic volume (Khorram et al., 2006), and increases in the volume of the basal ganglia (Lang et al., 2004) and lateral ventricles (Crespo-Facorro et al., 2008). However, this topic is controversial; furthermore, whether typical and atypical antipsychotic medication have the same effects on regional brain structure change in patients with schizophrenia remains disputable (Ebdrup et al., 2013; Lieberman et al., 2005; McClure et al., 2006; Navari and Dazzan, 2009; Smieskova et al., 2009). We recently reported that antipsychotic medication exposure predicted loss of total brain volume in schizophrenia over time (Veijola et al, 2014) even after controlling for symptom severity, alcohol use and weight gain; however, our recent study, like the majority of other papers on this topic, looked only at summary brain volume indices rather than a fine-grained (voxel or vertex based) level of resolution. "
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    ABSTRACT: Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions. Copyright © 2015. Published by Elsevier B.V.
    Schizophrenia Research 07/2015; 70(1). DOI:10.1016/j.schres.2015.06.016 · 3.92 Impact Factor
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    • "measures of CSP and may influence morphological alterations in brain regions related to CSP (Dickey et al., 2007; Chakos et al., 2005; McClure et al., 2006; Girgis et al., 2006), we examined the pattern of use of antipsychotics between groups. Fukuzako et al. (1996) found that higher doses of neuroleptics were used in patients of schizophrenia who had CSP. "
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    ABSTRACT: Like prevalence of abnormal cavum septum pellucidum in patients of schizophrenia remains controversial, its role in clinical outcome, duration of illness and effect on treatment remains less understood as well. Our study examined clinical correlates of enlarged cavum septum pellucidum in schizophrenia. A total of 139 patients diagnosed with schizophrenia during the year 2012 and 2013 were taken for the study. We compared them in respect to the presence and absence of enlarged cavum septum pellucidum. We found 16 patients with enlarged cavum septum pellucidum and were compared with those without enlarged cavum septum pellucidum for socio-demographic and clinical variables. We also correlated these clinical variables with dimension of cavum septum pellucidum. We found statistically significant increased current age and duration of illness in patients with enlarged cavum septum pellucidum. The implications of these findings are discussed with possible confounding effect of current age on neuroimaging. No meaningful correlation was found. No difference in clinical variables was found. Retrospective design and use of computed tomography were limitation of our study. Copyright © 2015 Elsevier B.V. All rights reserved.
    Asian Journal of Psychiatry 06/2015; 15:21-24. DOI:10.1016/j.ajp.2015.04.008
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    • "Treatment with olanzapine and risperidone has been associated with larger hippocampal volumes in patients with schizophrenia, compared to patients treated with haloperidol in a cross-sectional study [50]. Conversely, two longitudinal neuroimaging studies found no relationship between type of antipsychotic medication and hippocampal volume change [51], [52]. "
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    ABSTRACT: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs). We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024). The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.
    PLoS ONE 02/2014; 9(2):e87997. DOI:10.1371/journal.pone.0087997 · 3.23 Impact Factor
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