Skip to main content
×
Home
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 135
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Caseras, X Tansey, K E Foley, S and Linden, D 2015. Association between genetic risk scoring for schizophrenia and bipolar disorder with regional subcortical volumes. Translational Psychiatry, Vol. 5, Issue. 12, p. e692.


    Cannon, Tyrone D. 2015. How Schizophrenia Develops: Cognitive and Brain Mechanisms Underlying Onset of Psychosis. Trends in Cognitive Sciences, Vol. 19, Issue. 12, p. 744.


    Chatziioannou, Sofia N. and Rizos, Emmanouil N. 2014. Imaging of the Human Brain in Health and Disease.


    Weinmann, Stefan and Aderhold, Volkmar 2010. Antipsychotic medication, mortality and neurodegeneration: The need for more selective use and lower doses. Psychosis, Vol. 2, Issue. 1, p. 50.


    Perlini, C. Bellani, M. and Brambilla, P. 2012. Structural imaging techniques in schizophrenia. Acta Psychiatrica Scandinavica, Vol. 126, Issue. 4, p. 235.


    Remington, Gary Foussias, George Agid, Ofer Fervaha, Gagan Takeuchi, Hiroyoshi and Hahn, Margaret 2014. The neurobiology of relapse in schizophrenia. Schizophrenia Research, Vol. 152, Issue. 2-3, p. 381.


    GRANT, PHILLIP 2013. Letter to the Editor: Haloperidol but not dopamine rapidly induces neuronal death: comments on ‘A systematic review of the effects of antipsychotic drugs on brain volume’. Psychological Medicine, Vol. 43, Issue. 07, p. 1568.


    Moncrieff, J. and Leo, J. 2010. A systematic review of the effects of antipsychotic drugs on brain volume. Psychological Medicine, Vol. 40, Issue. 09, p. 1409.


    Ehlkes, Tim Michie, Patricia T and Schall, Ulrich 2012. Brain imaging correlates of emerging schizophrenia. Neuropsychiatry, Vol. 2, Issue. 2, p. 147.


    Aderhold, V. Weinmann, S. Hägele, C. and Heinz, A. 2015. Frontale Hirnvolumenminderung durch Antipsychotika?. Der Nervenarzt, Vol. 86, Issue. 3, p. 302.


    Borgwardt, Stefan McGuire, Philip and Fusar-Poli, Paolo 2011. Gray matters! — Mapping the transition to psychosis. Schizophrenia Research, Vol. 133, Issue. 1-3, p. 63.


    Breggin, Peter R. 2014. The Rights of Children and Parents In Regard to Children Receiving Psychiatric Diagnoses and Drugs. Children & Society, Vol. 28, Issue. 3, p. 231.


    Cannon, Tyrone D. 2016. Brain Biomarkers of Vulnerability and Progression to Psychosis. Schizophrenia Bulletin, Vol. 42, Issue. suppl 1, p. S127.


    Bentall, Professor Richard and Morrison, Professor Tony 2011. Letter to the editor. Psychosis, Vol. 3, Issue. 2, p. 177.


    Modinos, Gemma Allen, Paul Grace, Anthony A. and McGuire, Philip 2015. Translating the MAM model of psychosis to humans. Trends in Neurosciences, Vol. 38, Issue. 3, p. 129.


    Jiang, Tianzi Zhou, Yuan Liu, Bing Liu, Yong and Song, Ming 2013. Brainnetome-wide association studies in schizophrenia: The advances and future. Neuroscience & Biobehavioral Reviews, Vol. 37, Issue. 10, p. 2818.


    Zipursky, R. B. Reilly, T. J. and Murray, R. M. 2013. The Myth of Schizophrenia as a Progressive Brain Disease. Schizophrenia Bulletin, Vol. 39, Issue. 6, p. 1363.


    Vita, A De Peri, L Deste, G and Sacchetti, E 2012. Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Translational Psychiatry, Vol. 2, Issue. 11, p. e190.


    Emsley, Robin Asmal, Laila du Plessis, Stéfan Chiliza, Bonginkosi Kidd, Martin Carr, Jonathan and Vink, Matthijs 2015. Dorsal striatal volumes in never-treated patients with first-episode schizophrenia before and during acute treatment. Schizophrenia Research, Vol. 169, Issue. 1-3, p. 89.


    Brauns, Stefan Gollub, Randy L. Walton, Esther Hass, Johanna Smolka, Michael N. White, Tonya Wassink, Thomas H. Calhoun, Vince D. and Ehrlich, Stefan 2013. Genetic variation in GAD1 is associated with cortical thickness in the parahippocampal gyrus. Journal of Psychiatric Research, Vol. 47, Issue. 7, p. 872.


    ×

Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings

  • S. Navari (a1) (a2) and P. Dazzan (a1)
  • DOI: http://dx.doi.org/10.1017/S0033291709005315
  • Published online: 02 April 2009
Abstract
Background

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?

Method

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.

Results

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.

Conclusions

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.

Copyright
Corresponding author
*Address for correspondence: S. Navari, M.D., Ph.D., Psychiatrist and Research Associate, Division of Psychological Medicine and Psychiatry, PO Box 63, Institute of Psychiatry, De Crespigny Park, LondonSE 8AF, UK. (Email: serena.navari@iop.kcl.ac.uk)
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

KL Narr , AW Toga , P Szeszko , PM Thompson , RP Woods , D Robinson , S Sevy , Y Wang , K Schrock , RM Bilder (2005). Cortical thinning in cingulate and occipital cortices in first episode schizophrenia. Biological Psychiatry 58, 3240.

F Angelucci , L Aloe , A Iannitelli , SH Gruber , AA Mathe (2005). Effect of chronic olanzapine treatment on nerve growth factor and brain-derived neurotrophic factor in the rat brain. European Neuropsychopharmacology 15, 311317.

W Cahn , HE Hulshoff Pol , EB Lems , NE van Haren , HG Schnack , JA van der Linden , PF Schothorst , H van Engeland , RS Kahn (2002). Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59, 10021010.

PC Nopoulos , JW Ceilley , EA Gailis , NC Andreasen (2001). An MRI study of midbrain morphology in patients with schizophrenia: relationship to psychosis, neuroleptics, and cerebellar neural circuitry. Biological Psychiatry 49, 1319.

L Shihabuddin , MS Buchsbaum , EA Hazlett , MM Haznedar , PD Harvey , A Newman , DB Schnur , J Spiegel-Cohen , T Wei , J Machac , K Knesaurek , S Vallabhajosula , MA Biren , TM Ciaravolo , C Luu-Hsia (1998). Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task. Archives of General Psychiatry 55, 235243.

MH Chakos , JA Lieberman , J Alvir , R Bilder , M Ashtari (1995). Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine. Lancet 345, 456457.

MH Chakos , SA Schobel , H Gu , G Gerig , D Bradford , C Charles , JA Lieberman (2005). Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia. British Journal of Psychiatry 186, 2631.

J Christensen , J Holcomb , DL Garver (2004). State-related changes in cerebral white matter may underlie psychosis exacerbation. Psychiatry Research 130, 7178.

PW Corson , P Nopoulos , NC Andreasen , D Heckel , S Arndt (1999 a). Caudate size in first-episode neuroleptic-naive schizophrenic patients measured using an artificial neural network. Biological Psychiatry 46, 712720.

CE Dean (2006). Antipsychotic-associated neuronal changes in the brain: toxic, therapeutic, or irrelevant to the long-term outcome of schizophrenia? Progress in Neuropsychopharmacology and Biological Psychiatry 30, 174189.

RF Deicken , Y Eliaz , L Chosiad , R Feiwell , L Rogers (2002). Magnetic resonance imaging of the thalamus in male patients with schizophrenia. Schizophrenia Research 58, 135144.

KA Dorph-Petersen , JN Pierri , JM Perel , Z Sun , AR Sampson , DA Lewis (2005). The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 30, 16491661.

GE Duncan , S Zorn , JA Lieberman (1999). Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia. Molecular Psychiatry 4, 418428.

L Farde , H Hall , E Ehrin , G Sedvall (1986). Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231, 258261.

F Fumagalli , R Molteni , F Bedogni , M Pennarelli , J Perez , G Racagni , MA Riva (2004). Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals treated with MK-801. Neuroreport 15, 21092112.

DL Garver , JA Holcomb , JD Christensen (2005). Cerebral cortical gray expansion associated with two second-generation antipsychotics. Biological Psychiatry 58, 6266.

RR Girgis , VA Diwadkar , JJ Nutche , JA Sweeney , MS Keshavan , AY Hardan (2006). Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study. Schizophrenia Research 82, 8994.

RE Gur , P Cowell , BI Turetsky , F Gallacher , T Cannon , W Bilker , RC Gur (1998 a). A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Archives of General Psychiatry 55, 145152.

RE Gur , PE Cowell , A Latshaw , BI Turetsky , RI Grossman , SE Arnold , WB Bilker , RC Gur (2000). Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Archives of General Psychiatry 57, 761768.

RE Gur , V Maany , PD Mozley , C Swanson , W Bilker , RC Gur (1998 b). Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. American Journal of Psychiatry 155, 17111717.

ND Halim , CS Weickert , BW McClintock , DR Weinberger , BK Lipska (2004). Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus. Neuropsychopharmacology 29, 10631069.

DR Heitmiller , PC Nopoulos , NC Andreasen (2004). Changes in caudate volume after exposure to atypical neuroleptics in patients with schizophrenia may be sex-dependent. Schizophrenia Research 66, 137142.

BC Ho , NC Andreasen , P Nopoulos , S Arndt , V Magnotta , M Flaum (2003). Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Archives of General Psychiatry 60, 585594.

HE Hulshoff Pol , RS Kahn (2008). What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophrenia Bulletin 34, 354366.

MS Keshavan , WW Bagwell , GL Haas , JA Sweeney , NR Schooler , JW Pettegrew (1994). Changes in caudate volume with neuroleptic treatment. Lancet 344, 1434.

B Khorram , DJ Lang , LC Kopala , RA Vandorpe , Q Rui , VM Goghari , GN Smith , WG Honer (2006). Reduced thalamic volume in patients with chronic schizophrenia after switching from typical antipsychotic medications to olanzapine. American Journal of Psychiatry 163, 20052007.

DJ Lang , LC Kopala , RA Vandorpe , Q Rui , GN Smith , VM Goghari , WG Honer (2001). An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. American Journal of Psychiatry 158, 625631.

DJ Lang , LC Kopala , RA Vandorpe , Q Rui , GN Smith , VM Goghari , JS Lapointe , WG Honer (2004). Reduced basal ganglia volumes after switching to olanzapine in chronically treated patients with schizophrenia. American Journal of Psychiatry 161, 18291836.

SM Lawrie , SS Abukmeil (1998). Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172, 110120.

J Lieberman , M Chakos , H Wu , J Alvir , E Hoffman , D Robinson , R Bilder (2001). Longitudinal study of brain morphology in first episode schizophrenia. Biological Psychiatry 49, 487499.

JA Lieberman , GD Tollefson , C Charles , R Zipursky , T Sharma , RS Kahn , RS Keefe , AI Green , RE Gur , J McEvoy , D Perkins , RM Hamer , H Gu , M Tohen (2005). Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry 62, 361370.

G Massana , P Salgado-Pineda , C Dunque , M Perez , I Baeza , A Pons , J Massana , V Navarro , J Blanch , A Morer , JM Mercader , M Bernardo (2005). Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone. Journal of Clinical Psychopharmacology 25, 111117.

DH Mathalon , EV Sullivan , KO Lim , A Pfefferbaum (2001). Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Archives of General Psychiatry 58, 148157.

RW McCarley , CG Wible , M Frumin , Y Hirayasu , JJ Levitt , IA Fischer , ME Shenton (1999). MRI anatomy of schizophrenia. Biological Psychiatry 45, 10991119.

RK McClure , I Phillips , R Jazayerli , A Barnett , R Coppola , DR Weinberger (2006). Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment. Psychiatry Research 148, 121132.

MJ Millan (2005). N-Methyl-D-aspartate receptors as a target for improved antipsychotic agents: novel insights and clinical perspectives. Psychopharmacology (Berlin) 179, 3053.

DD Miller , NC Andreasen , DS O'Leary , K Rezai , GL Watkins , LL Ponto , RD Hichwa (1997 a). Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography. Neuropsychopharmacology 17, 230240.

DD Miller , NC Andreasen , DS O'Leary , GL Watkins , LL Boles Ponto , RD Hichwa (2001). Comparison of the effects of risperidone and haloperidol on regional cerebral blood flow in schizophrenia. Biological Psychiatry 49, 704715.

DD Miller , K Rezai , R Alliger , NC Andreasen (1997 b). The effect of antipsychotic medication on relative cerebral blood perfusion in schizophrenia: assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography. Biological Psychiatry 41, 550559.

S Nyberg , B Eriksson , G Oxenstierna , C Halldin , L Farde (1999). Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients. American Journal of Psychiatry 156, 869875.

P Oosthuizen , R Emsley , H Jadri Turner , N Keyter (2004). A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis. International Journal of Neuropsychopharmacology 7, 125131.

C Pantelis , D Velakoulis , PD McGorry , SJ Wood , J Suckling , LJ Phillips , AR Yung , ET Bullmore , W Brewer , B Soulsby , P Desmond , PK McGuire (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281288.

BK Puri , SB Hutton , N Saeed , A Oatridge , JV Hajnal , L Duncan , MJ Chapman , TR Barnes , GM Bydder , EM Joyce (2001). A serial longitudinal quantitative MRI study of cerebral changes in first-episode schizophrenia using image segmentation and subvoxel registration. Psychiatry Research 106, 141150.

FE Scheepers , CC de Wied , HE Hulshoff Pol , W van de Flier , JA van der Linden , RS Kahn (2001 a). The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics. Neuropsychopharmacology 24, 4754.

FE Scheepers , CC Gispen de Wied , HE Hulshoff Pol , RS Kahn (2001 b). Effect of clozapine on caudate nucleus volume in relation to symptoms of schizophrenia. American Journal of Psychiatry 158, 644646.

H Scherk , P Falkai (2006). Effects of antipsychotics on brain structure. Current Opinion in Psychiatry 19, 145150.

P Seeman (2005). An update of fast-off dopamine D2 atypical antipsychotics. American Journal of Psychiatry 162, 19841985.

ME Shenton , CC Dickey , M Frumin , RW McCarley (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 152.

S Tauscher-Wisniewski , J Tauscher , J Logan , BK Christensen , DJ Mikulis , RB Zipursky (2002). Caudate volume changes in first episode psychosis parallel the effects of normal aging: a 5-year follow-up study. Schizophrenia Research 58, 185188.

S Taylor , JD Christensen , JM Holcomb , DL Garver (2005). Volume increases in striatum associated with positive symptom reduction in schizophrenia: a preliminary observation. Psychiatry Research 140, 8589.

PM Thompson , C Vidal , JN Giedd , P Gochman , J Blumenthal , R Nicolson , AW Toga , JL Rapoport (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proceedings of the National Academy of USA 98, 1165011655.

D Velakoulis , C Pantelis , PD McGorry , P Dudgeon , W Brewer , M Cook , P Desmond , N Bridle , P Tierney , V Murrie , B Singh , D Copolov (1999). Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. Archives of General Psychiatry 56, 133141.

HD Wang , FD Dunnavant , T Jarman , AY Deutch (2004). Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29, 12301238.

DR Weinberger , RK McClure (2002). Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain? Archives of General Psychiatry 59, 553558.

AM Wright , J Bempong , ML Kirby , RL Barlow , JR Bloomquist (1998). Effects of haloperidol metabolites on neurotransmitter uptake and release: possible role in neurotoxicity and tardive dyskinesia. Brain Research 788, 215222.

RB Zipursky , J Zhang-Wong , EK Lambe , G Bean , M Beiser (1998). MRI correlates of treatment response in first episode psychosis. Schizophrenia Research 30, 8190.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Type Description Title
UNKNOWN
Supplementary Materials

Navari supplementary material
Tables.pdf

 Unknown (61 KB)
61 KB