Navari S, Dazzan P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med 39: 1763-1777

Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, UK.
Psychological Medicine (Impact Factor: 5.94). 05/2009; 39(11):1763-77. DOI: 10.1017/S0033291709005315
Source: PubMed


The potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type?
A systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: 'antipsychotics' AND 'brain' AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed.
Thirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal.
Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.

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Available from: Paola Dazzan, Apr 10, 2015
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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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    • "There were even two studies reporting an absence of progressive brain changes in patients over the first 2–3 years of follow-up (James et al., 2002; James et al., 2004). Discrepant volumetric findings in young people may be at least partly attributable to different factors and conditions that moderate the detected pattern of structural brain changes, i.e., 1) differences in sex proportion (Lenroot et al., 2007; Janssen et al., 2012), 2) age at onset (Vita et al., 2012), 3) duration of illness (Haijma et al., 2013), 4) duration of follow-up (Vita et al., 2012; Haijma et al., 2013), 5) brain regions of interest (ROIs) under study (Arango et al., 2008), 6) use of voxelbased morphometry (VBM) versus ROI-based approaches (Giuliani et al., 2005), 7) exposure to lithium or antipsychotic treatment (Navari and Dazzan, 2009; Ho et al., 2011; Hafeman et al., 2012; Fusar-Poli et al., 2013; Haijma et al., 2013), 8) symptom presentation and severity (DeLisi et al., 1998; Strakowski et al., 2002; Nery et al., 2009; Arango et al., 2012), and 9) diagnostic heterogeneity (Arango et al., 2008; Arango et al., 2012). Childhood-onset schizophrenia (COS) is defined as schizophrenia with onset prior to age 13 years. "
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    ABSTRACT: Studies on longitudinal brain volume changes in patients with early-onset psychosis (EOP) are particularly valuable for understanding the neurobiological basis of brain abnormalities associated with psychosis. However, findings have not been consistent across studies in this population. We aimed to conduct a meta-analysis on progressive brain volume changes in children and adolescents with EOP. A systematic literature search of magnetic resonance imaging (MRI) studies comparing longitudinal brain volume changes in children and adolescents with EOP and healthy controls was conducted. The annualized rates of relative change in brain volume by region of interest (ROI) were used as raw data for the meta-analysis. The effect of age, sex, duration of illness, and specific diagnosis on volume change was also evaluated. Five original studies with 156 EOP patients (mean age at baseline MRI in the five studies ranged from 13.3 to 16.6years, 67.31% males) and 163 age- and sex-matched healthy controls, with a mean duration of follow-up of 2.46years (range 2.02-3.40), were included. Frontal gray matter (GM) was the only region in which significant differences in volume change over time were found between patients and controls (Hedges' g -0.435, 95% confidence interval (CI): -0.678 to -0.193, p<0.001). Younger age at baseline MRI was associated with greater loss of temporal GM volume over time in patients as compared with controls (p=0.005). Within patients, a diagnosis of schizophrenia was related to greater occipital GM volume loss over time (p=0.001). Compared with healthy individuals, EOP patients show greater progressive frontal GM loss over the first few years after illness onset. Age at baseline MRI and diagnosis of schizophrenia appear to be significant moderators of particular specific brain volume changes. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; DOI:10.1016/j.schres.2014.12.022 · 3.92 Impact Factor
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    • "Atypical antipsychotics and cannabis have been associated with brain structural change (46, 47) and were widely used in our patients. Based on two systematic reviews, antipsychotics may alter gray matter volume (48, 49). However, there has been no consensus regarding the directionality of the effect (i.e., increasing or decreasing). "
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    ABSTRACT: Negative symptoms occur in several major mental health disorders with undetermined mechanisms and unsatisfactory treatments; identification of their neural correlates might unveil the underlying pathophysiological basis and pinpoint the therapeutic targets. In this study, participants with major depressive disorder (n = 24), schizophrenia (n = 22), and healthy controls (n = 20) were assessed with 10 frequently used negative symptom scales followed by principal component analysis (PCA) of the scores. A linear model with the prominent components identified by PCA was then regressed on gray and white-matter volumes estimated from T1-weighted magnetic resonance imaging. In depressed patients, negative symptoms such as blunted affect, alogia, withdrawal, and cognitive impairment, assessed mostly via clinician-rated scales were inversely associated with gray matter volume in the bilateral cerebellum. In patients with schizophrenia, anhedonia, and avolition evaluated via self-rated scales inversely related to white-matter volume in the left anterior limb of internal capsule/anterior thalamic radiation and positively in the left superior longitudinal fasiculus. The pathophysiological mechanisms underlying negative symptoms might differ between depression and schizophrenia. These results also point to future negative symptom scale development primarily focused on detecting and monitoring the corresponding changes to brain structure or function.
    Frontiers in Psychiatry 08/2014; 5:116. DOI:10.3389/fpsyt.2014.00116
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