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A systematic review of the effects of antipsychotic drugs on brain volume

Published online by Cambridge University Press:  20 January 2010

J. Moncrieff  and
J. Leo
J. Moncrieff*
Affiliation:
Department of Mental Health Sciences, University College London, UK
J. Leo
Affiliation:
Department of Anatomy, Lincoln Memorial University, Harrogate, TN, USA
*
*Address for correspondence: Dr J. Moncrieff, Department of Mental Health Sciences, University College London, Charles Bell House, 67-73, Riding House Street, London, WIW7EJ, UK. (Email: [email protected])
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Abstract

Background

People with schizophrenia are often found to have smaller brains and larger brain ventricles than normal, but the role of antipsychotic medication remains unclear.

Method

We conducted a systematic review of magnetic resonance imaging (MRI) studies. We included longitudinal studies of brain changes in patients taking antipsychotic drugs and we examined studies of antipsychotic-naive patients for comparison purposes.

Results

Fourteen out of 26 longitudinal studies showed a decline in global brain or grey-matter volume or an increase in ventricular or cerebrospinal fluid (CSF) volume during the course of drug treatment, including the largest studies conducted. The frontal lobe was most consistently affected, but overall changes were diffuse. One large study found different degrees of volume loss with different antipsychotics, and another found that volume changes were associated with taking medication compared with taking none. Analyses of linear associations between drug exposure and brain volume changes produced mixed results. Five out of 21 studies of patients who were drug naive, or had only minimal prior treatment, showed some differences from controls in volumes of interest. No global differences were reported in three studies of drug-naive patients with long-term illness. Studies of high-risk groups have not demonstrated differences from controls in global or lobar brain volumes.

Conclusions

Some evidence points towards the possibility that antipsychotic drugs reduce the volume of brain matter and increase ventricular or fluid volume. Antipsychotics may contribute to the genesis of some of the abnormalities usually attributed to schizophrenia.

Keywords

Antipsychoticsbrain volumeMRIneuroimagingschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 40 , Issue 9 , September 2010 , pp. 1409 - 1422
Copyright
Copyright © Cambridge University Press 2010

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References

Arango, C, Moreno, C, Martinez, S, Parellada, M, Desco, M, Moreno, D, Fraguas, D, Gogtay, N, James, A, Rapoport, J (2008). Longitudinal brain changes in early-onset psychosis. Schizophrenia Bulletin 34, 341–353.CrossRefGoogle ScholarPubMed
Arnone, D, Cavanagh, J, Gerber, D, Lawrie, SM, Ebmeier, KP, McIntosh, AM (2009). Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. British Journal of Psychiatry 195, 194–201.CrossRefGoogle ScholarPubMed
Bachmann, S, Bottmer, C, Pantel, J, Schroder, J, Amann, M, Essig, M, Schad, LR (2004). MRI-morphometric changes in first-episode schizophrenic patients at 14 months follow-up. Schizophrenia Research 67, 301–303.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, Riecher-Rossler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, Gschwandtner, U, Haller, S, Pfluger, M, Rechsteiner, E, D'Souza, M, Stieglitz, RD, Radu, EW, McGuire, PK (2007). Regional gray matter volume abnormalities in the at risk mental state. Biological Psychiatry 61, 1148–1156.CrossRefGoogle ScholarPubMed
Bottmer, C, Bachmann, S, Pantel, J, Essig, M, Amann, M, Schad, LR, Magnotta, V, Schroder, J (2005). Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia. Psychiatry Research 140, 239–250.CrossRefGoogle ScholarPubMed
Bruton, CJ, Crow, TJ, Frith, CD, Johnstone, EC, Owens, DG, Roberts, GW (1990). Schizophrenia and the brain: a prospective clinico-neuropathological study. Psychological Medicine 20, 285–304.CrossRefGoogle Scholar
Buchsbaum, MS, Someya, T, Teng, CY, Abel, L, Chin, S, Najafi, A, Haier, RJ, Wu, J, Bunney, Jr. WE (1996). PET and MRI of the thalamus in never-medicated patients with schizophrenia. American Journal of Psychiatry 153, 191–199.Google ScholarPubMed
Cahn, W, Hulshoff Pol, HE, Bongers, M, Schnack, HG, Mandl, RC, van Haren, NE, Durston, S, Koning, H, van der Linden, JA, Kahn, RS (2002 a). Brain morphology in antipsychotic-naive schizophrenia: a study of multiple brain structures. British Journal of Psychiatry (Suppl.) 43, s66–s72.CrossRefGoogle ScholarPubMed
Cahn, W, Hulshoff Pol, HE, Lems, EB, van Haren, NE, Schnack, HG, van der Linden, JA, Schothorst, PF, van Engeland, H, Kahn, RS (2002 b). Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59, 1002–1010.CrossRefGoogle ScholarPubMed
Cahn, W, Rais, M, Stigter, FP, van Haren, NE, Caspers, E, Hulshoff Pol, HE, Xu, Z, Schnack, HG, Kahn, RS (2009). Psychosis and brain volume changes during the first five years of schizophrenia. European Neuropsychopharmacology 19, 147–151.CrossRefGoogle ScholarPubMed
Chakos, MH, Lieberman, JA, Alvir, J, Bilder, R, Ashtari, M (1995). Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine. Lancet 345, 456–457.CrossRefGoogle ScholarPubMed
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
Crespo-Facorro, B, Roiz-Santianez, R, Perez-Iglesias, R, Pelayo-Teran, JM, Rodriguez-Sanchez, JM, Tordesillas-Gutierrez, D, Ramirez, M, Martinez, O, Gutierrez, A, de Lucas, EM, Vazquez-Barquero, JL (2008). Effect of antipsychotic drugs on brain morphometry. A randomized controlled one-year follow-up study of haloperidol, risperidone and olanzapine. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 1936–1943.CrossRefGoogle ScholarPubMed
Davatzikos, C, Shen, D, Gur, RC, Wu, X, Liu, D, Fan, Y, Hughett, P, Turetsky, BI, Gur, RE (2005). Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities. Archives of General Psychiatry 62, 1218–1227.CrossRefGoogle ScholarPubMed
Dazzan, P, Morgan, KD, Orr, K, Hutchinson, G, Chitnis, X, Suckling, J, Fearon, P, McGuire, PK, Mallett, RM, Jones, PB, Leff, J, Murray, RM (2005). Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study. Neuropsychopharmacology 30, 765–774.CrossRefGoogle ScholarPubMed
Dazzan, P, Morgan, K, Reinders, AAST, Morgan, C, Fearon, P, Zanelli, J, Fisher, H, Jones, P, Murray, R, McGuire, P, Lappin, J (2008). Grey and white matter volume changes 6 years after the onset of psychosis. Schizophrenia Research 102 (Suppl. 2), 69.CrossRefGoogle Scholar
Dean, CE (2006). Antipsychotic-associated neuronal changes in the brain: toxic, therapeutic, or irrelevant to the long-term outcome of schizophrenia? Progress in Neuro-Psychopharmacology and Biological Psychiatry 30, 174–189.CrossRefGoogle ScholarPubMed
DeLisi, LE, Hoff, AL, Schwartz, JE, Shields, GW, Halthore, SN, Gupta, SM, Henn, FA, Anand, AK (1991). Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study. Biological Psychiatry 29, 159–175.CrossRefGoogle ScholarPubMed
DeLisi, LE, Sakuma, M, Maurizio, AM, Relja, M, Hoff, AL (2004). Cerebral ventricular change over the first 10 years after the onset of schizophrenia. Psychiatry Research 130, 57–70.CrossRefGoogle ScholarPubMed
DeLisi, LE, Sakuma, M, Tew, W, Kushner, M, Hoff, AL, Grimson, R (1997). Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiatry Research 74, 129–140.CrossRefGoogle Scholar
Dorph-Petersen, KA, Pierri, JN, Perel, JM, Sun, Z, Sampson, AR, Lewis, DA (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, 1649–1661.CrossRefGoogle ScholarPubMed
Ettinger, U, Chitnis, XA, Kumari, V, Fannon, DG, Sumich, AL, O'Ceallaigh, S, Doku, VC, Sharma, T (2001). Magnetic resonance imaging of the thalamus in first-episode psychosis. American Journal of Psychiatry 158, 116–118.CrossRefGoogle ScholarPubMed
Gilbert, AR, Rosenberg, DR, Harenski, K, Spencer, S, Sweeney, JA, Keshavan, MS (2001). Thalamic volumes in patients with first-episode schizophrenia. American Journal of Psychiatry 158, 618–624.CrossRefGoogle ScholarPubMed
Gogtay, N, Sporn, A, Clasen, LS, Nugent, TF III, Greenstein, D, Nicolson, R, Giedd, JN, Lenane, M, Gochman, P, Evans, A, Rapoport, JL (2004). Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. Archives of General Psychiatry 61, 17–22.CrossRefGoogle ScholarPubMed
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
Gur, RE, Turetsky, BI, Bilker, WB, Gur, RC (1999). Reduced gray matter volume in schizophrenia. Archives of General Psychiatry 56, 905–911.CrossRefGoogle ScholarPubMed
Harrison, PJ (1999 a). The neuropathological effects of antipsychotic drugs. Schizophrenia Research 40, 87–99.CrossRefGoogle ScholarPubMed
Harrison, PJ (1999 b). The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122, 593–624.CrossRefGoogle ScholarPubMed
Ho, BC, Andreasen, NC, Nopoulos, P, Arndt, S, Magnotta, V, Flaum, M (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, 585–594.CrossRefGoogle ScholarPubMed
Hulshoff Pol, HE, Kahn, RS (2008). What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophrenia Bulletin 34, 354–366.CrossRefGoogle ScholarPubMed
Ichimiya, T, Okubo, Y, Suhara, T, Sudo, Y (2001). Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia. Biological Psychiatry 49, 20–27.CrossRefGoogle ScholarPubMed
James, AC, James, S, Smith, DM, Javaloyes, A (2004). Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia. American Journal of Psychiatry 161, 1023–1029.CrossRefGoogle ScholarPubMed
Jayakumar, PN, Venkatasubramanian, G, Gangadhar, BN, Janakiramaiah, N, Keshavan, MS (2005). Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29, 587–591.CrossRefGoogle ScholarPubMed
John, JP, Burgess, PW, Yashavantha, BS, Shakeel, MK, Halahalli, HN, Jain, S (2009). Differential relationship of frontal pole and whole brain volumetric measures with age in neuroleptic-naive schizophrenia and healthy subjects. Schizophrenia Research 109, 148–158.CrossRefGoogle ScholarPubMed
Joyal, CC, Laakso, MP, Tiihonen, J, Syvalahti, E, Vilkman, H, Laakso, A, Alakare, B, Rakkolainen, V, Salokangas, RK, Hietala, J (2002). A volumetric MRI study of the entorhinal cortex in first episode neuroleptic-naive schizophrenia. Biological Psychiatry 51, 1005–1007.CrossRefGoogle ScholarPubMed
Joyal, CC, Laakso, MP, Tiihonen, J, Syvalahti, E, Vilkman, H, Laakso, A, Alakare, B, Rakkolainen, V, Salokangas, RK, Hietala, J (2003). The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naive patients. Biological Psychiatry 54, 1302–1304.CrossRefGoogle ScholarPubMed
Kasai, K, Shenton, ME, Salisbury, DF, Hirayasu, Y, Lee, CU, Ciszewski, AA, Yurgelun-Todd, D, Kikinis, R, Jolesz, FA, McCarley, RW (2003 a). Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia. American Journal of Psychiatry 160, 156–164.CrossRefGoogle ScholarPubMed
Kasai, K, Shenton, ME, Salisbury, DF, Hirayasu, Y, Onitsuka, T, Spencer, MH, Yurgelun-Todd, DA, Kikinis, R, Jolesz, FA, McCarley, RW (2003 b). Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Archives of General Psychiatry 60, 766–775.CrossRefGoogle ScholarPubMed
Keshavan, MS, Haas, GL, Kahn, CE, Aguilar, E, Dick, EL, Schooler, NR, Sweeney, JA, Pettegrew, JW (1998 a). Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? Journal of Psychiatric Research 32, 161–167.CrossRefGoogle ScholarPubMed
Keshavan, MS, Rosenberg, D, Sweeney, JA, Pettegrew, JW (1998 b). Decreased caudate volume in neuroleptic-naive psychotic patients. American Journal of Psychiatry 155, 774–778.Google ScholarPubMed
Khorram, B, Lang, DJ, Kopala, LC, Vandorpe, RA, Rui, Q, Goghari, VM, Smith, GN, Honer, WG (2006). Reduced thalamic volume in patients with chronic schizophrenia after switching from typical antipsychotic medications to olanzapine. American Journal of Psychiatry 163, 2005–2007.CrossRefGoogle ScholarPubMed
Lacerda, AL, Hardan, AY, Yorbik, O, Vemulapalli, M, Prasad, KM, Keshavan, MS (2007). Morphology of the orbitofrontal cortex in first-episode schizophrenia: relationship with negative symptomatology. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 510–516.CrossRefGoogle ScholarPubMed
Lawrie, SM, Whalley, HC, Abukmeil, SS, Kestelman, JN, Donnelly, L, Miller, P, Best, JJ, Owens, DG, Johnstone, EC (2001). Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia. Biological Psychiatry 49, 811–823.CrossRefGoogle ScholarPubMed
Lawrie, SM, Whalley, HC, Abukmeil, SS, Kestelman, JN, Miller, P, Best, JJ, Owens, DG, Johnstone, EC (2002). Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms. British Journal of Psychiatry 181, 138–143.CrossRefGoogle ScholarPubMed
Lieberman, J, Chakos, M, Wu, H, Alvir, J, Hoffman, E, Robinson, D, Bilder, R (2001). Longitudinal study of brain morphology in first episode schizophrenia. Biological Psychiatry 49, 487–499.CrossRefGoogle ScholarPubMed
Lieberman, JA, Tollefson, GD, Charles, C, Zipursky, R, Sharma, T, Kahn, RS, Keefe, RS, Green, AI, Gur, RE, McEvoy, J, Perkins, D, Hamer, RM, Gu, H, Tohen, M (2005). Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry 62, 361–370.CrossRefGoogle ScholarPubMed
Lui, S, Deng, W, Huang, X, Jiang, L, Ma, X, Chen, H, Zhang, T, Li, X, Li, D, Zou, L, Tang, H, Zhou, XJ, Mechelli, A, Collier, DA, Sweeney, JA, Li, T, Gong, Q (2009). Association of cerebral deficits with clinical symptoms in antipsychotic-naive first–episode schizophrenia: an optimized voxel-based morphometry and resting state functional connectivity study. American Journal of Psychiatry 166, 196–205.CrossRefGoogle ScholarPubMed
MacMaster, FP, El Sheikh, R, Upadhyaya, AR, Nutche, J, Rosenberg, DR, Keshavan, M (2007). Effect of antipsychotics on pituitary gland volume in treatment-naive first-episode schizophrenia: a pilot study. Schizophrenia Research 92, 207–210.CrossRefGoogle ScholarPubMed
Mathalon, DH, Sullivan, EV, Lim, KO, Pfefferbaum, A (2001). Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Archives of General Psychiatry 58, 148–157.CrossRefGoogle Scholar
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: Neuroimaging 148, 121–132.CrossRefGoogle ScholarPubMed
McCreadie, RG, Thara, R, Padmavati, R, Srinivasan, TN, Jaipurkar, SD (2002). Structural brain differences between never-treated patients with schizophrenia, with and without dyskinesia, and normal control subjects: a magnetic resonance imaging study. Archives of General Psychiatry 59, 332–336.CrossRefGoogle ScholarPubMed
Molina, V, Reig, S, Sanz, J, Palomo, T, Benito, C, Sanchez, J, Sarramea, F, Pascau, J, Desco, M (2005). Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia. Schizophrenia Research 80, 61–71.CrossRefGoogle ScholarPubMed
Molina, V, Sanz, J, Benito, C, Palomo, T (2004). Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia. International Clinical Psychopharmacology 19, 221–228.CrossRefGoogle ScholarPubMed
Moorhead, TW, McKirdy, J, Sussmann, JE, Hall, J, Lawrie, SM, Johnstone, EC, McIntosh, AM (2007). Progressive gray matter loss in patients with bipolar disorder. Biological Psychiatry 62, 894–900.CrossRefGoogle ScholarPubMed
Moreno, D, Burdalo, M, Reig, S, Parellada, M, Zabala, A, Desco, M, Baca-Baldomero, E, Arango, C (2005). Structural neuroimaging in adolescents with a first psychotic episode. Journal of the American Academy of Child and Adolescent Psychiatry 44, 1151–1157.CrossRefGoogle ScholarPubMed
Nair, TR, Christensen, JD, Kingsbury, SJ, Kumar, NG, Terry, WM, Garver, DL (1997) Progression of cerebroventricular enlargement and the subtyping of schizophrenia. Psychiatry Research 74, 141–150.CrossRefGoogle ScholarPubMed
Nakamura, M, Salisbury, DF, Hirayasu, Y, Bouix, S, Pohl, KM, Yoshida, T, Koo, MS, Shenton, ME, McCarley, RW (2007). Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study. Biological Psychiatry 62, 773–783.CrossRefGoogle ScholarPubMed
Narr, KL, Bilder, RM, Toga, AW, Woods, RP, Rex, DE, Szeszko, PR, Robinson, D, Sevy, S, Gunduz-Bruce, H, Wang, YP, Deluca, H, Thompson, PM (2005). Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex 15, 708–719.CrossRefGoogle ScholarPubMed
Narr, KL, Thompson, PM, Szeszko, P, Robinson, D, Jang, S, Woods, RP, Kim, S, Hayashi, KM, Asunction, D, Toga, AW, Bilder, RM (2004). Regional specificity of hippocampal volume reductions in first-episode schizophrenia. NeuroImage 21, 1563–1575.CrossRefGoogle ScholarPubMed
Navari, S, Dazzan, P (2009). Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychological Medicine 39, 1763–1777.CrossRefGoogle ScholarPubMed
Okugawa, G, Nobuhara, K, Takase, K, Kinoshita, T (2007) Cerebellar posterior superior vermis and cognitive cluster scores in drug-naive patients with first-episode schizophrenia. Neuropsychobiology 56, 216–219.CrossRefGoogle ScholarPubMed
Owens, DG, Johnstone, EC, Crow, TJ, Frith, CD, Jagoe, JR, Kreel, L (1985). Lateral ventricular size in schizophrenia: relationship to the disease process and its clinical manifestations. Psychological Medicine 15, 27–41.CrossRefGoogle Scholar
Panenka, WJ, Khorram, B, Barr, AM, Smith, GN, Lang, DJ, Kopala, LC, Vandorpe, RA, Honer, WG (2007). A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia. Schizophrenia Research 94, 288–292.CrossRefGoogle ScholarPubMed
Prasad, KM, Patel, AR, Muddasani, S, Sweeney, J, Keshavan, MS (2004 a). The entorhinal cortex in first-episode psychotic disorders: a structural magnetic resonance imaging study. American Journal of Psychiatry 161, 1612–1619.CrossRefGoogle ScholarPubMed
Prasad, KM, Rohm, BR, Keshavan, MS (2004 b). Parahippocampal gyrus in first episode psychotic disorders: a structural magnetic resonance imaging study. Progress in Neuro-Psychopharmacology and Biological Psychiatry 28, 651–658.CrossRefGoogle ScholarPubMed
Puri, BK, Hutton, SB, Saeed, N, Oatridge, A, Hajnal, JV, Duncan, L, Chapman, MJ, Barnes, TR, Bydder, GM, Joyce, EM (2001). A serial longitudinal quantitative MRI study of cerebral changes in first-episode schizophrenia using image segmentation and subvoxel registration. Psychiatry Research 106, 141–150.CrossRefGoogle ScholarPubMed
Rapoport, JL, Giedd, JN, Blumenthal, J, Hamburger, S, Jeffries, N, Fernandez, T, Nicolson, R, Bedwell, J, Lenane, M, Zijdenbos, A, Paus, T, Evans, A (1999) Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study. Archives of General Psychiatry 56 649–654.CrossRefGoogle ScholarPubMed
Reig, S, Moreno, C, Moreno, D, Burdalo, M, Janssen, J, Parellada, M, Zabala, A, Desco, M, Arango, C (2009). Progression of brain volume changes in adolescent-onset psychosis. Schizophrenia Bulletin 35, 233–243.CrossRefGoogle ScholarPubMed
Saijo, T, Abe, T, Someya, Y, Sassa, T, Sudo, Y, Suhara, T, Shuno, T, Asai, K, Okubo, Y (2001). Ten year progressive ventricular enlargement in schizophrenia: an MRI morphometrical study. Psychiatry and Clinical Neurosciences 55, 41–47.CrossRefGoogle ScholarPubMed
Salgado-Pineda, P, Baeza, I, Perez-Gomez, M, Vendrell, P, Junque, C, Bargallo, N, Bernardo, M (2003) Sustained attention impairment correlates to gray matter decreases in first episode neutroleptic-naive schizophrenic patients. Neuroimage 19, 365–375.CrossRefGoogle ScholarPubMed
Schaufelberger, MS, Duran, FL, Lappin, JM, Scazufca, M, Amaro, Jr. E, Leite, CC, de Castro, CC, Murray, RM, McGuire, PK, Menezes, PR, Busatto, GF (2007). Grey matter abnormalities in Brazilians with first-episode psychosis. British Journal of Psychiatry (Suppl.) 51, s117–s122.CrossRefGoogle ScholarPubMed
Scherk, H, Falkai, P (2006). Effects of antipsychotics on brain structure. Current Opinion in Psychiatry 19, 145–150.CrossRefGoogle ScholarPubMed
Schulz, SC, Koller, M, Kishore, PR, Hamer, RM, Friedel, RO (1982). Abnormal scans in young schizophrenics. Psychopharmacological Bulletin 18, 163–164.Google ScholarPubMed
Selemon, LD, Lidow, MS, Goldman-Rakic, PS (1999). Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biological Psychiatry 46, 161–172.CrossRefGoogle ScholarPubMed
Sporn, AL, Greenstein, DK, Gogtay, N, Jeffries, NO, Lenane, M, Gochman, P, Clasen, LS, Blumenthal, J, Giedd, JN, Rapoport, JL (2003). Progressive brain volume loss during adolescence in childhood-onset schizophrenia. American Journal of Psychiatry 160, 2181–2189.CrossRefGoogle ScholarPubMed
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510–518.CrossRefGoogle ScholarPubMed
Sullivan, EV, Shear, PK, Lim, KO, Zipursky, RB, Pfefferbaum, A (1996). Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia. Biological Psychiatry 39, 234–240.CrossRefGoogle ScholarPubMed
Takahashi, T, Wood, SJ, Soulsby, B, McGorry, PD, Tanino, R, Suzuki, M, Velakoulis, D, Pantelis, C (2009 a). Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophrenia Research 108, 49–56.CrossRefGoogle ScholarPubMed
Takahashi, T, Wood, SJ, Yung, AR, Phillips, LJ, Soulsby, B, McGorry, PD, Tanino, R, Zhou, SY, Suzuki, M, Velakoulis, D, Pantelis, C (2009 b). Insular cortex gray matter changes in individuals at ultra-high-risk of developing psychosis. Schizophrenia Research 111, 94–102.CrossRefGoogle ScholarPubMed
Takahashi, T, Wood, SJ, Yung, AR, Soulsby, B, McGorry, PD, Suzuki, M, Kawasaki, Y, Phillips, LJ, Velakoulis, D, Pantelis, C (2009 c). Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Archives of General Psychiatry 66, 366–376.CrossRefGoogle ScholarPubMed
Tauscher-Wisniewski, S, Tauscher, J, Christensen, BK, Mikulis, DJ, Zipursky, RB (2005) Volumetric MRI measurement of caudate nuclei in antipsychotic-naive patients suffering from a first episode of psychosis. Journal of Psychiatry Research 39, 365–370.CrossRefGoogle ScholarPubMed
Theberge, J, Williamson, KE, Aoyama, N, Drost, DJ, Manchanda, R, Malla, AK, Northcott, S, Menon, RS, Neufeld, RW, Rajakumar, N, Pavlosky, W, Densmore, M, Schaefer, B, Williamson, PC (2007). Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia. British Journal of Psychiatry 191, 325–334.CrossRefGoogle ScholarPubMed
Torrey, EF (2002). Studies of individuals with schizophrenia never treated with antipsychotic medications: a review. Schizophrenia Research 58, 101–115.CrossRefGoogle ScholarPubMed
Upadhyaya, AR, El Sheikh, R, MacMaster, FP, Diwadkar, VA, Keshavan, MS (2007). Pituitary volume in neuroleptic-naive schizophrenia: a structural MRI study. Schizophrenia Research 90, 266–273.CrossRefGoogle ScholarPubMed
van Haren, NE, Pol, HE, Schnack, HG, Cahn, W, Brans, R, Carati, I, Rais, M, Kahn, RS (2008). Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biological Psychiatry 63, 106–113.CrossRefGoogle ScholarPubMed
Venkatasubramanian, G, Jayakumar, PN, Gangadhar, BN, Keshavan, MS (2008). Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naive schizophrenia. Acta Psychiatrica Scandinavica 117, 420–431.CrossRefGoogle ScholarPubMed
Vita, A, De Peri, L (2007). The effects of antipsychotic treatment on cerebral structure and function in schizophrenia. International Review of Psychiatry 19, 429–436.CrossRefGoogle ScholarPubMed
Weinberger, DR, DeLisi, LE, Perman, GP, Targum, S, Wyatt, RJ (1982). Computed tomography in schizophreniform disorder and other acute psychiatric disorders. Archives of General Psychiatry 39, 778–783.CrossRefGoogle ScholarPubMed
Whitford, TJ, Grieve, SM, Farrow, TF, Gomes, L, Brennan, J, Harris, AW, Gordon, E, Williams, LM (2006). Progressive grey matter atrophy over the first 2–3 years of illness in first-episode schizophrenia: a tensor-based morphometry study. NeuroImage 32, 511–519.CrossRefGoogle ScholarPubMed
Whitworth, AB, Kemmler, G, Honeder, M, Kremser, C, Felber, S, Hausmann, A, Walch, T, Wanko, C, Weiss, EM, Stuppaeck, CH, Fleischhacker, WW (2005). Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients. Psychiatry Research 140, 225–237.CrossRefGoogle ScholarPubMed
Wood, SJ, Velakoulis, D, Smith, DJ, Bond, D, Stuart, GW, McGorry, PD, Brewer, WJ, Bridle, N, Eritaia, J, Desmond, P, Singh, B, Copolov, D, Pantelis, C (2001). A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophrenia Research 52, 37–46.CrossRefGoogle ScholarPubMed
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed