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Antipsychotic medication and longitudinal changes in brain volume in schizophrenia

Antipsychotic medication and longitudinal changes in brain volume in schizophrenia - meta-analysis and results from the Northern Finland 1966 Birth Cohort Study. Jouko Miettunen jouko.miettunen@oulu.fi Department of Psychiatry, University of Oulu, Finland. Conflicts of interest: None.

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Antipsychotic medication and longitudinal changes in brain volume in schizophrenia

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  1. Antipsychotic medication and longitudinal changes in brain volume in schizophrenia - meta-analysis and results from the Northern Finland 1966 Birth Cohort Study Jouko Miettunen jouko.miettunen@oulu.fi Department of Psychiatry, University of Oulu, Finland

  2. Conflicts of interest:None

  3. SYSTEMATIC REVIEW AND META-ANALYSIS • Relatively little is known on factors associating with longitudinal changes in brain morphometry in schizophrenia after the illness onset. • Our aim was to systematically review longitudinal MRI studies with at least two-year scan-interval on the relation between the dose or type of antipsychotic medication and brain morphometric changes in schizophrenia and related psychoses.

  4. Previous reviews • decreases in grey matter and global brain volume and increments in cerebrospinal fluid (CSF) or ventricular volume during drug treatment • contradictory findings when comparing typical and atypical medications • basal ganglia volume increment after treatment with especially typical antipsychotics • have included also short follow-ups! Moncrieff & Leo (Psychol Med 2010); Navari & Dazzan (Psychol Med 2009); Smieskova et al. (Curr Pharm Des 2009); Shepherd et al. (Neurosci Biobehav Rev 2012); Fusar-Poli et al. (Neurosci Biobehav Rev 2013)

  5. meta-analysis • Studies were systematically collected using the databases of PubMed, Scopus, Web of Knowledge, and PsycINFO (1223 hits). • We calculated correlations between antipsychotic dose and brain volume changes. • 2-year scan-interval was required • Results reported only as “non-significant” were also included (correlation = zero)

  6. meta-analysis brain regions (12) • total brain, cerebrum, frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebellum, limbic area, basal ganglia, pituitary gland, paracentral lobule, and CSF and ventricles. brain tissue types (4) • grey matter (GM), white matter (WM), CSF, and volumes

  7. FE = first episode, PT = previously treated

  8. meta-analysis • Most (83%) of the reported correlations were statistically non-significant. • In the studies with significant findings, use of antipsychotics more often associated with decrease than increase of brain volumes, even in the very few studies taking into account illness severity.

  9. meta-analysis by tissue type and brain area combinations

  10. Statistically significant findings ***=large (r ≤ 0.5), **=moderate (0.3 ≤ r < 0.5), *=small (r > 0.1), ^=smaller than 0.1 correlation

  11. meta-analysis • In performed meta-analyses of specific brain areas no significant associations were found. • We did not find any clear differences between typical and atypical exposure and brain volume change. • Studies focusing on first episode patients were more likely to find an effect than studies on previously treated patients. • In the studies with significant findings in grey matter, high antipsychotic dose was more frequently associated with decrease (27% of correlations) than with increase (10%).

  12. Northern Finland 1966 Birth Cohort • All members of the general population-based Northern Finland Birth Cohort 1966 with any psychotic disorder were invited for a MRI brain scan at the age of 34 years. • A follow-up was conducted on average 9 years later. • Brain scans at both time points were obtained from 33 subjects with schizophrenia.

  13. scan-interval antipsychotic cumulative dose associated with total brain volume loss, even when adjusted with symptoms (beta =-0.43, p=0.018). SOFAS = Social and Occupational Functioning Assessment Scale, PANSS = Positive and Negative Syndrome Scale Veijola J, et al. Manuscript

  14. conclusions • Antipsychotic medication may contribute to changes in brain structure in some areas of the brain. • The current available data is inconclusive and therefore more good quality long-term follow-up studies are needed focusing on the possible association between antipsychotic medication and brain structures. • Covariates ? • severity of illness, substance abuse, smoking, duration of illness • Combine data sets ?

  15. Sanna Huhtaniska, BMed; Juha Veijola, prof.; Matti Isohanni, prof.; Erika Jääskeläinen, MScD;Jouko Miettunen, PhD • Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland & Department of Psychiatry, Oulu University Hospital, Oulu, Finland Noora Hirvonen, MA • Information Studies, Faculty of Humanities, University of Oulu, Oulu, Finland Jukka Remes, MSc • Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland Graham K Murray, MScD • Department of Psychiatry, University of Cambridge, Cambridge, UK Email: jouko.miettunen@oulu.fi

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