Bendfeldt, K.

Borgwardt, S. J.

Fusar-Poli, P.

Riecher-Rössler, A.

Smieskova, R.

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The eﬀects of antipsychotics on brain structure:what have we learnt from structural imagingof schizophrenia?A commentary on ‘Do antipsychotic drugs aﬀect brain structure? A systematic and critical reviewof MRI ﬁndings ’ by Navari & Dazzan (2009)S. J. Borgwardt1,2,3*, R. Smieskova1,2, P. Fusar-Poli3, K. Bendfeldt2 and A. Riecher-Ro¨ssler11 Psychiatric Outpatient Department, 2 Medical Image Analysis Centre, University Hospital Basel, Switzerland3 Section of Neuroimaging, King’s College London, Institute of Psychiatry, London, UKReceived 11 April 2009 ; Accepted 22 April 2009 ; First published online 29 May 2009Key words : Antipsychotics, ARMS, brain structure, MRI, schizophrenia.IntroductionWe read with great interest the article by Navari &Dazzan (2009) recently published in Psychological Medi-cine. These authors found that antipsychotic treatmentmay contribute to brain structural changes observedin psychosis and that antipsychotics act regionallyrather than globally on the brain, with speciﬁc eﬀectson diﬀerent brain structures.In an own systematic review on the eﬀects of anti-psychotics on the brain (Smieskova et al. in press) wesummarized ﬁndings from structural imaging studiesof schizophrenia. We focused on studies investigat-ing schizophrenia patients using neuroimaging tech-niques according to antipsychotic medication andstudies considering the diﬀerences in medicationeither in various antipsychotic medications or overthe time or in various groups of patients. Overall,we found that patients with schizophrenia receiv-ing treatment with antipsychotics had reduced greymatter (GM) volume, particularly in frontal and tem-poral lobes. Medication with typical antipsychoticsalso leads to increased volume of the basal ganglia,while atypical antipsychotics reversed the eﬀect afterswitching. Studies with typical antipsychotics havereported increased GM volume in cingulate cortex,in contrast to atypical antipsychotics with the excessmore often seen in thalamus volume.Confounding eﬀects of antipsychoticsAs discussed by Navari & Dazzan (2009), the potentialconfounding impact of antipsychotics on progressivebrain changes in schizophrenia is considered contro-versial (DeLisi, 2008). Although there is evidence forGM loss and ventricular enlargement from prospec-tive studies of patients with ﬁrst-episode and chronicschizophrenia (Wood et al. 2008), most neuroimagingstudies of schizophrenia to date have not included theexamination of non-medicated patients, making con-clusions about medication eﬀects on neuroimagingmeasures diﬃcult. Investigation of subjects at the on-set of the disease avoids potential confounders suchas antipsychotic treatment (Riecher-Rossler et al. 2007).A clinical high-risk status for psychosis (at-risk mentalstate, ARMS) is associated with a set of neurofunc-tional abnormalities that are qualitatively similar tothose observed in patients with the disorder (Fusar-Poli et al. 2007). As these ﬁndings are not attributableto chronic psychotic symptoms or antipsychotic treat-ment, they may solely represent markers of increasedvulnerability to psychotic disorders. Cross-sectionalstructural MRI studies of non-medicated patients in aprodromal phase of psychosis or ARMS demonstratedthat neuroanatomical abnormalities are already evi-dent in the very early phase of psychosis (Wood et al.2008) whereas longitudinal MRI studies found that thesubset of patients who developed psychosis showeda longitudinal reduction in GM in the orbito-frontal,temporal lobe, parietal lobe and cerebellum (Panteliset al. 2003 ; Job et al. 2005 ; Borgwardt et al. 2008).Conclusions and future directionsNeuroimaging studies have provided compelling evi-dence that despite antipsychotic medication (bothtypical and atypical) there are detectable anatomicalchanges at the level of total and regional brain vol-umes. To date, it remains elusive whether the eﬀects ofantipsychotic medication on GM volume are simply* Address for correspondence : Dr S. J. Borgwardt, PsychiatricOutpatient Department, University Hospital Basel, Petersgraben 4,CH-4031 Basel, Switzerland.(Email : sborgwardt@uhbs.ch)Psychological Medicine (2009), 39, 1781–1782. f Cambridge University Press 2009doi:10.1017/S0033291709006060 Printed in the United KingdomCOMMENTARYhttps:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0033291709006060Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 17:03:20, subject to the Cambridge Core terms of use, available atbeneﬁcial. Experimental studies of macaque monkeysshowed that chronic administration of either halo-peridol or olanzapine was associated with smaller GMvolume (Konopaske et al. 2008). These results, if con-ﬁrmed, raise ethical questions on antipsychotic use.If antipsychotic medication may lead – at least in somepatients – to GM volume reduction careful beneﬁt–risk decisions have to be made for individual patients.Patients with schizophrenia should be very carefullyinformed about the potential risks (and of coursebeneﬁts) of antipsychotic medication.It is questionable whether the eﬀects we are obser-ving are the direct eﬀects of antipsychotics or due tothe illness process. Until we have more reliable studiesfrom non-medicated patients, the potential impactof the confounding eﬀect of medication must be bornein mind. For future studies, we therefore suggestfocusing on longitudinal designs that represent thegold standard for investigation of medication eﬀects.These studies clearly have the advantage of powerful,within-subject designs. Small sample sizes, hetero-geneity in the sociodemographic characteristics ofsubjects, and lack of consistency between scanningparameters should be addressed by future multi-sitestudies that have shown the potential to overcomemost of these problems and to bridge basic neuro-science with clinical psychiatry. So far, the investi-gation of patients at risk or with a ﬁrst episodeof schizophrenia seems to be the most promisingalternative.AcknowledgementsThis research was supported by the Swiss NationalScience Foundation (PBBSB-106936) and the NovartisFoundation. The sponsor of the study had no rolein study design, collection, analysis, interpretation ofdata, writing of this report, or in the decision to submitthe paper for publication.Declaration of InterestNone.ReferencesBorgwardt SJ, McGuire PK, Aston J, Gschwandtner U,Pﬂuger MO, Stieglitz RD, Radue EW, Riecher-Rossler A(2008). Reductions in frontal, temporal and parietal volumeassociated with the onset of psychosis. SchizophreniaResearch 106, 108–114.DeLisi LE (2008). Reviewing the ‘ facts about schizophrenia ’ :a possible or impossible task? Schizophrenia Research 102,19–20.Fusar-Poli P, Perez J, BroomeM, Borgwardt S, Placentino A,Caverzasi E, Cortesi M, Veggiotti P, Politi P, Barale F,McGuire P (2007). Neurofunctional correlates ofvulnerability to psychosis : a systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews 31, 465–484.Job DE, Whalley HC, Johnstone EC, Lawrie SM (2005).Grey matter changes over time in high risk subjectsdeveloping schizophrenia. Neuroimage 25, 1023–1030.Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri JN,ZhangW, Sampson AR, Lewis DA (2008). Eﬀect of chronicantipsychotic exposure on astrocyte and oligodendrocytenumbers in macaque monkeys. Biological Psychiatry 63,759–765.Navari S, Dazzan P (2009). Do antipsychotic drugs aﬀectbrain structure? A systematic and critical review of MRIﬁndings. Psychological Medicine. Published online : 2 April2009. doi :10.1017/S0033291709005315.Pantelis C, Velakoulis D, McGorry PD, Wood SJ,Suckling J, Phillips LJ, Yung AR, Bullmore ET, BrewerW, Soulsby B, Desmond P, McGuire PK (2003).Neuroanatomical abnormalities before and after onset ofpsychosis : a cross-sectional and longitudinal MRIcomparison. Lancet 361, 281–288.Riecher-Rossler A, Gschwandtner U, Aston J, Borgwardt S,Drewe M, Fuhr P, Pﬂuger M, Radu W, Schindler C,Stieglitz RD (2007). The Basel early-detection-of-psychosis(FEPSY) study – design and preliminary results. ActaPsychiatrica Scandinavica 115, 114–125.Smieskova R, Fusar-Poli P, Allen P, Bendfeldt K,Stieglitz RD, Drewe J, Radu EW, McGuire PK, Riecher A,Borgwardt SJ (in press). The eﬀects of antipsychotics onthe brain : What have we learnt from structuralneuroimaging of schizophrenia? – a systematic review.Current Pharmaceutical Design.Wood SJ, Pantelis C, Velakoulis D, Yucel M, Fornito A,McGorry PD (2008). Progressive changes in thedevelopment toward schizophrenia : studies in subjectsat increased symptomatic risk. Schizophrenia Bulletin 34,322–329.1782 S. J. Borgwardt et al.https:/www.cambridge.org/core/terms. https://doi.org/10.1017/S0033291709006060Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 30 May 2017 at 17:03:20, subject to the Cambridge Core terms of use, available at

The effects of antipsychotics on brain structure: what have we learnt from structural imaging of schizophrenia?: A commentary on ‘Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings' by Navari & Dazzan (2009)

The effects of antipsychotics on brain structure: what have we learnt from structural imaging of schizophrenia?: A commentary on ‘Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings' by Navari & Dazzan (2009)

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