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Early striatal hypertrophy in first-episode psychosis within 3 weeks of initiating antipsychotic drug treatment

Published online by Cambridge University Press:  20 August 2008

S. E. Chua ,
Y. Deng ,
E. Y. H. Chen ,
C. W. Law ,
C. P. Y. Chiu ,
C. Cheung ,
J. C. H. Wong ,
N. Lienenkaëmper ,
V. Cheung  and
J. Suckling
...Show all authors
S. E. Chua
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China State Key Laboratory for Cognitive Science, The University of Hong Kong, S.A.R. China
Y. Deng
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
E. Y. H. Chen
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
C. W. Law
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
C. P. Y. Chiu
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
C. Cheung
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
J. C. H. Wong
Affiliation:
Faculty of Medicine, University of Georgetown, Washington, DC, USA
N. Lienenkaëmper
Affiliation:
Department of Biomedical Sciences, The University of Utrecht, The Netherlands
V. Cheung
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China
J. Suckling
Affiliation:
Cambridge Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK
G. M. McAlonan*
Affiliation:
Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, S.A.R. China State Key Laboratory for Cognitive Science, The University of Hong Kong, S.A.R. China
*
*Address for correspondence: Dr G. M. McAlonan, Department of Psychiatry, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, S.A.R. China. (Email: [email protected])
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Abstract

Background

We and others have reported that patients experiencing their first episode of psychosis already have significant structural brain abnormalities. Antipsychotics seem to reverse subcortical volume deficits after months of treatment. However, the early impact of medication on brain morphology is not known.

Method

Forty-eight individuals in their first episode of psychosis underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were antipsychotic naive and 22 were newly treated with antipsychotic medication for a median period of 3 weeks. In each group, 80% of subjects received a diagnosis of schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity, height, years of education, paternal socio-economic status (SES) and Positive and Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey matter were compared voxel by voxel, using Brain Activation and Morphological Mapping (BAMM) software. We also conducted testing of group differences with region-of-interest (ROI) measurements of the caudate nucleus.

Results

Relative to the untreated group, those receiving antipsychotic medication for 3–4 weeks had significantly greater grey-matter volumes in the bilateral caudate and cingulate gyri, extending to the left medial frontal gyrus. ROI analysis confirmed that, in treated patients, the right and left caudate nuclei were significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed) respectively.

Conclusions

Early striatal grey-matter enlargement may occur within the first 3–4 weeks of antipsychotic treatment. Possible reasons for putative striatal hypertrophy and its implications are discussed.

Keywords

Antipsychoticbrainfirst episodeMRIschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 5 , May 2009 , pp. 793 - 800
Copyright
Copyright © Cambridge University Press 2008

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References

Agid, O, Kapur, S, Warrington, L, Loebel, A, Siu, C (2008). Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders. Schizophrenia Research 102, 241–248.CrossRefGoogle ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC.Google Scholar
Barta, PE, Dhingra, L, Royall, R, Schwartz, E (1997). Improving stereological estimates for the volume of structures identified in three-dimensional arrays of spatial data. Journal of Neuroscience Methods 75, 111–118.Google Scholar
Bullmore, ET, Suckling, J, Overmeyer, S, Rabe-Hesketh, S, Taylor, E, Brammer, MJ (1999). Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Transactions on Medical Imaging 18, 32–42.Google Scholar
Chakos, MH, Lieberman, JA, Bilder, RM, Borenstein, M, Lerner, G, Bogerts, B, Wu, H, Kinon, B, Ashtari, M (1994). Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. American Journal of Psychiatry 151, 1430–1436.Google Scholar
Chen, EY, Dunn, EL, Miao, MY, Yeung, WS, Wong, CK, Chan, WF, Chen, RY, Chung, KF, Tang, WN (2005). The impact of family experience on the duration of untreated psychosis (DUP) in Hong Kong. Social Psychiatry and Psychiatric Epidemiology 40, 350–356.Google Scholar
Chua, SE, Cheung, C, Cheung, V, Tsang, JT, Chen, EY, Wong, JC, Cheung, JP, Yip, L, Tai, KS, Suckling, J, McAlonan, GM (2007). Cerebral grey, white matter and CSF in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 12–21.CrossRefGoogle ScholarPubMed
Corson, PW, Nopoulos, P, Andreasen, NC, Heckel, D, Arndt, S (1999). Caudate size in first-episode neuroleptic-naive schizophrenic patients measured using an artificial neural network. Biological Psychiatry 46, 712–720.Google Scholar
Corson, PW, O'Leary, DS, Miller, DD, Andreasen, NC (2002). The effects of neuroleptic medications on basal ganglia blood flow in schizophreniform disorders: a comparison between the neuroleptic-naive and medicated states. Biological Psychiatry 52, 855–862.CrossRefGoogle ScholarPubMed
Crespo-Facorro, B, Perez-Iglesias, R, Ramirez-Bonilla, M, Martinez-Garcia, O, Llorca, J, Vazquez-Barquero, JL (2006). A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis. Journal of Clinical Psychiatry 67, 1511–1521.CrossRefGoogle ScholarPubMed
Dazzan, P, Morgan, KD, Orr, KG, Hutchinson, G, Chitnis, X, Suckling, J, Fearon, P, Salvo, J, McGuire, PK, Mallett, RM, Jones, PB, Leff, J, Murray, RM (2004). The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study. Brain 127, 143–153.Google Scholar
Garver, DL, Holcomb, JA, Christensen, JD (2005). Cerebral cortical gray expansion associated with two second-generation antipsychotics. Biological Psychiatry 58, 62–66.Google Scholar
Girgis, RR, Diwadkar, VA, Nutche, JJ, Sweeney, JA, Keshavan, MS, Hardan, AY (2006). Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study. Schizophrenia Research 82, 89–94.Google Scholar
Gur, RE, Cowell, P, Turetsky, BI, Gallacher, F, Cannon, T, Bilker, W, Gur, RC (1998). A follow-up magnetic resonance imaging study of schizophrenia: relationship of neuroanatomical changes to clinical and neurobehavioral measures. Archives of General Psychiatry 55, 145–152.CrossRefGoogle ScholarPubMed
Hafner, H, Riecher-Rossler, A, Hambrecht, M, Maurer, K, Meissner, S, Schmidtke, A, Fatkenheuer, B, Loffler, W, van der Heiden, W (1992). IRAOS: an instrument for the assessment of onset and early course of schizophrenia. Schizophrenia Research 6, 209–223.CrossRefGoogle ScholarPubMed
Harrison, PJ (1999). The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 122, 593–624.Google Scholar
Jayakumar, PN, Venkatasubramanian, G, Keshavan, MS, Srinivas, JS, Gangadhar, BN (2006). MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in antipsychotic-naive schizophrenia. Acta Psychiatrica Scandinavica 114, 346–351.Google Scholar
Johnstone, EC, Crow, TJ, Frith, CD, Carney, MW, Price, JS (1978). Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet 1, 848–851.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Keshavan, MS (1999). Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. Journal of Psychiatric Research 33, 513–521.Google Scholar
Kippin, TE, Kapur, S, van der Kooy, D (2005). Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. Journal of Neuroscience 25, 5815–5823.Google Scholar
Konradi, C, Heckers, S (2001). Antipsychotic drugs and neuroplasticity: insights into the treatment and neurobiology of schizophrenia. Biological Psychiatry 50, 729–742.Google Scholar
Laruelle, M (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain-imaging studies. Brain Research Reviews 31, 371–384.CrossRefGoogle ScholarPubMed
Leucht, S, Busch, R, Hamann, J, Kissling, W, Kane, JM (2005). Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended. Biological Psychiatry 57, 1543–1549.CrossRefGoogle Scholar
Massana, G, Salgado-Pineda, P, Junque, C, Perez, M, Baeza, I, Pons, A, Massana, J, Navarro, V, Blanch, J, Morer, A, Mercader, JM, Bernardo, M (2005). Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone. Journal of Clinical Psychopharmacology 25, 111–117.Google Scholar
McAlonan, GM, Cheung, V, Cheung, C, Suckling, J, Lam, GY, Tai, KS, Yip, L, Murphy, DG, Chua, SE (2005). Mapping the brain in autism: a voxel-based MRI study of volumetric differences and intercorrelations in autism. Brain 128, 268–276.CrossRefGoogle ScholarPubMed
McAlonan, GM, Daly, E, Kumari, V, Critchley, HD, van Amelsvoort, T, Suckling, J, Simmons, A, Sigmundsson, T, Greenwood, K, Russell, A, Schmitz, N, Happe, F, Howlin, P, Murphy, DG (2002). Brain anatomy and sensorimotor gating in Asperger's syndrome. Brain 125, 1594–1606.CrossRefGoogle ScholarPubMed
McClure, RK, Phillips, I, Jazayerli, R, Barnett, A, Coppola, R, Weinberger, DR (2006). Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment. Psychiatry Research 148, 121–132.Google Scholar
Murphy, DG, DeCarli, C, Schapiro, MB, Rapoport, SI, Horwitz, B (1992). Age-related differences in volumes of subcortical nuclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging. Archives of Neurology 49, 839–845.Google Scholar
Pilowsky, LS (2001). Probing targets for antipsychotic drug action with PET and SPET receptor imaging. Nuclear Medicine Communications 22, 829–833.Google Scholar
Rushworth, MF, Buckley, MJ, Behrens, TE, Walton, ME, Bannerman, DM (2007). Functional organization of the medial frontal cortex. Current Opinion in Neurobiology 17, 220–227.Google Scholar
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 1–52.Google Scholar
Sigmundsson, T, Suckling, J, Maier, M, Williams, S, Bullmore, E, Greenwood, K, Fukuda, R, Ron, M, Toone, B (2001). Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. American Journal of Psychiatry 158, 234–243.CrossRefGoogle ScholarPubMed
Suckling, J, Brammer, MJ, Lingford-Hughes, A, Bullmore, ET (1999 a). Removal of extracerebral tissues in dual-echo magnetic resonance images via linear scale-space features. Magnetic Resonance Imaging 17, 247–256.Google Scholar
Suckling, J, Bullmore, E (2004). Permutation tests for factorially designed neuroimaging experiments. Human Brain Mapping 22, 193–205.Google Scholar
Suckling, J, Sigmundsson, T, Greenwood, K, Bullmore, ET (1999 b). A modified fuzzy clustering algorithm for operator independent brain tissue classification of dual echo MR images. Magnetic Resonance Imaging 17, 1065–1076.Google Scholar
Tamminga, CA, Vogel, M, Gao, X, Lahti, AC, Holcomb, HH (2000). The limbic cortex in schizophrenia: focus on the anterior cingulate. Brain Research Reviews 31, 364–370.Google Scholar
Thompson, PM, Vidal, C, Giedd, JN, Gochman, P, Blumenthal, J, Nicolson, R, Toga, AW, Rapoport, JL (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proceedings of the National Academy of Sciences USA 98, 11650–11655.Google Scholar
Talairach, J, Tournoux, P (1988). Co-planar Stereotaxic Atlas of the Human Brain. Thieme: Stuttgart.Google Scholar
Wang, H-D, Dunnavant, FD, Jarman, T, Deutch, AY (2004). Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29, 1230–1238.Google Scholar
Weinberger, DR, Lipska, BK (1995). Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophrenia Research 16, 87–110.Google Scholar