Skip to main content Accessibility help
×
Home

Volume increases in putamen associated with positive symptom reduction in previously drug-naive schizophrenia after 6 weeks antipsychotic treatment

  • M. Li (a1), Z. Chen (a1), W. Deng (a1), Z. He (a1), Q. Wang (a1), L. Jiang (a1), X. Ma (a2), Y. Wang (a2), S. E. Chua (a3), C. Cheung (a3), G. M. McAlonan (a3), P. C. Sham (a3), D. A. Collier (a4), Q. Gong (a5) and T. Li (a1) (a2)...

Abstract

Background

Brain structure appears to alter after antipsychotic administration, but it is unknown whether these alterations are associated with improvement of psychopathology in patients with schizophrenia. In this study, the authors explore this relationship.

Method

Altogether, 66 first-episode, drug-naive patients with schizophrenia and 23 well-matched healthy controls underwent brain magnetic resonance imaging scans at baseline. All 23 healthy controls and 42 of the patients were rescanned after 6 weeks follow-up. The patients received regular antipsychotic treatment during the 6-week period and their psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and 6 weeks. The difference in PANSS scores between baseline and 6 weeks was expressed as a ratio of the scores at baseline – ‘PANSS reduction ratio’. A modified tensor-based morphometry procedure was applied to analyse longitudinal images. Correlations between regional volume changes, PANSS reduction ratio and antipsychotic drug dosages were explored.

Results

Compared with healthy controls, there was a significant increase in grey-matter volume of the right putamen in patients after 6 weeks treatment. This volume change was positively correlated with a positive PANSS reduction score but not related to drug dosages.

Conclusions

Putaminal volume increased after 6 weeks antipsychotic treatment in first-episode schizophrenia. The increased volume was closely correlated with improved psychopathology, suggesting the putamen might be a biomarker to predict the treatment response in schizophrenia.

Copyright

Corresponding author

*Address for correspondence: Professor T. Li, Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. (Email: xuntao26@hotmail.com)

References

Hide All
Abi-Dargham, A (2004). Do we still believe in the dopamine hypothesis? New data bring new evidence. International Journal of Neuropsychopharmacology 7, S1S5.
Agid, O, Kapur, S, Arenovich, T, Zipursky, RB (2003). Delayed-onset hypothesis of antipsychotic action – a hypothesis tested and rejected. Archives of General Psychiatry 60, 12281235.
Annett, M (1970). A classification of hand preference by association analysis. British Journal of Psychiatry 61, 303321.
Ashburner, J, Friston, KJ (2004). Morphometry. In Human Brain Function (ed. Frackowiak, R. S. J.). Academic Press, Elsevier Science: California, USA.
Atkins, M, Burgess, A, Bottomley, C, Riccio, M (1997). Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psychiatric Bulletin 21, 224226.
Backman, L, Ginovart, N, Dixon, RA, Wahlin, TBR, Wahlin, A, Halldin, C, Farde, L (2000). Age-related cognitive deficits mediated by changes in the striatal dopamine system. American Journal of Psychiatry 157, 635637.
Beckmann, H, Lauer, M (1997). The human striatum in schizophrenia. II. Increased number of striatal neurons in schizophrenics. Psychiatry Research Neuroimaging 68, 99–109.
Beng-Choon, H, Andreasen, NC, Ziebell, S, Pierson, R, Magnotta, V (2011). Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry 68, 128137.
Boonstra, G, van Haren, N, Schnack, HG, Cahn, W, Burger, H, Boersma, M, de Kroon, B, Grobbee, DE, Hulshoff Pol, HE, Kahn, RS (2011). Brain volume changes after withdrawal of atypical antipsychotics in patients with first-episode schizophrenia. Journal of Clinical Psychopharmacology 31, 146153.
Borta, A, Hoglinger, GU (2007). Dopamine and adult neurogenesis. Journal of Neurochemistry 100, 587595.
Chakos, MH, Lieberman, JA, Bilder, RM, Borenstein, M, Lerner, G, Bogerts, B, Wu, HW, Kinon, B, Ashtari, M (1994). Increase in caudate nuclei volumes of first-episode schizophrenia-patients taking antipsychotic-drugs. American Journal of Psychiatry 151, 14301436.
Chua, SE, Cheung, C, Cheung, V, Tsang, JTK, Chen, EYH, Wong, JCH, Cheung, JPY, Yip, L, Tai, KS, Suckling, J, McAlonan, GM (2007). Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 1221.
Chua, SE, Deng, Y, Chen, EYH, Law, CW, Chiu, CPY, Cheung, C, McAlonan, GM (2009). Early striatal hypertrophy in first-episode psychosis within 3 weeks of initiating antipsychotic drug treatment. Psychological Medicine 39, 793800.
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, 765774.
Deng, MY, McAlonan, GM, Cheung, C, Chiu, CPY, Law, CW, Cheung, V, Sham, PC, Chen, EYH, Chua, SE (2009). A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naive, newly diagnosed schizophrenia. Psychopharmacology 206, 437446.
Emsley, R, Rabinowitz, J, Medori, R (2006). Time course for antipsychotic treatment response in first-episode schizophrenia. American Journal of Psychiatry 163, 743745.
Falkai, P, Wobrock, T, Lieberman, J, Glenthoj, B, Gattaz, WF, Moller, HJ (2005). World Federation of Societies of Biological Psychiatry (WFSBP) – guidelines for biological treatment of schizophrenia. Part 1: Acute treatment of schizophrenia. World Journal of Biological Psychiatry 6, 132191.
First, MB, Spitzer, RL, Gibbon, M, Williams, JB (1996). Structured Clinical Interview for DSM-IV Axis I Disorders—Non-Patient Edition (SCID-I/NP), version 2.0. New York State Psychiatric Institute, Biometrics Research: New York.
Glenthoj, A, Glenthoj, BY, Mackeprang, T, Pagsberg, AK, Hemmingsen, RP, Jernigan, TL, Baare, WFC (2007). Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug. Psychiatry Research: Neuroimaging 154, 199208.
Gunduz, H, Wu, HW, Ashtari, M, Bogerts, B, Crandall, D, Robinson, DG, Alvir, J, Lieberman, J, Kane, J, Bilder, R (2002). Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects. Biological Psychiatry 51, 801808.
Gur, RE, Maany, V, Mozley, D, Swanson, C, Bilker, W, Gur, RC (1998). Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. American Journal of Psychiatry 155, 17111717.
Harris, MSH, Reilly, JL, Keshavan, MS, Sweeney, JA (2006). Longitudinal studies of antisaccades in antipsychotic-naive first-episode schizophrenia. Psychological Medicine 36, 485494.
Heinz, A, Schlagenhauf, F (2010). Dopaminergic dysfunction in schizophrenia: salience attribution revisited. Schizophrenia Bulletin 36, 472485.
Honea, R, Crow, TJ, Passingham, D, Mackay, CE (2005). Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. American Journal of Psychiatry 162, 22332245.
Howes, OD, Kapur, S (2009). The dopamine hypothesis of schizophrenia: version III-025EF. The final common pathway. Schizophrenia Bulletin 35, 549562.
Huang, XQ, Lui, S, Deng, W, Chan, RCK, Wu, QZ, Jiang, LJ, Zhang, JR, Jia, ZY, Li, F, Li, XL, Chen, L, Li, T, Gong, QY (2009). Localization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI. NeuroImage 49, 29012906.
Ifthikharuddin, SF, Shrier, DA, Numaguchi, Y, Tang, X, Ning, R, Shibata, DK, Kurlan, R (2000). MR volumetric analysis of the human basal ganglia: normative data. Academic Radiology 7, 627634.
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 & Biological Psychiatry 29, 587591.
Jentsch, JD, Roth, RH (1999). The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20, 201225.
Kawasaki, Y, Suzuki, M, Takahashi, T, Nohara, S, McGuire, PK, Seto, H, Kurachi, M (2008). Anomalous cerebral asymmetry in patients with schizophrenia demonstrated by voxel-based morphometry. Biological Psychiatry 63, 793800.
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.
Keilhoff, G, Grecksch, G, Bernstein, HG, Roskoden, T, Becker, A (2010). Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. European Archives of Psychiatry & Clinical Neuroscience 260, 151162.
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, 58155823.
Konradi, C, Heckers, S (2001). Antipsychotic drugs and neuroplasticity: insights into the treatment and neurobiology of schizophrenia. Biological Psychiatry 50, 729742.
Lahti, AC, Weiler, MA, Holcomb, HH, Tamminga, CA, Cropsey, KL (2009). Modulation of limbic circuitry predicts treatment response to antipsychotic medication: a functional imaging study in schizophrenia. Neuropsychopharmacology 34, 26752690.
Lang, DJ, Kopala, LC, Vandorpe, RA, Rui, Q, Smith, GN, Goghari, VM, Honer, WG (2001). An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. American Journal of Psychiatry 158, 625631.
Larisch, R, Meyer, W, Klimke, A, Kehren, F, Vosberg, H, Muller-Gartner, HW (1998). Left-right asymmetry of striatal dopamine D2 receptors. Nuclear Medicine Communication 19, 781787.
Lehman, AF, Lieberman, JA, Dixon, LB, McGlashan, TH, Miller, AL, Perkins, DO, Kreyenbuhl, J, McIntyre, JS, Charles, SC, Altshuler, K, Cook, I, Cross, CD, Mellman, L, Moench, LA, Norquist, G, Twemlow, SW, Woods, S, Yager, J, Gray, SH, Askland, K, Pandya, R, Prasad, K, Johnston, R, Nininger, J, Peele, R, Anzia, DJ, Benson, RS, Lurie, L, Walker, RD, Kunkle, R, Simpson, A, Fochtmann, LJ, Hart, C, Regier, D (2004). Practice guideline for the treatment of patients with schizophrenia, second edition. American Journal of Psychiatry 161, 156.
Leow, AD, Klunder, AD, Jack, CR, Toga, AW, Dale, AM, Bernstein, MA, Britson, PJ, Gunter, JL, Ward, CP, Whitwell, JL, Borowski, BJ, Fleisher, AS, Fox, NC, Harvey, D, Kornak, J, Schuff, N, Studholme, C, Alexander, GE, Weiner, MW, Thompson, PM (2006). Longitudinal stability of MRI for mapping brain change using tensor-based morphometry. NeuroImage 31, 627640.
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, 15431549.
Lui, S, Deng, W, Huang, XQ, Jiang, LJ, Ma, XH, Chen, HF, Zhang, TJ, Li, XL, Li, DM, Zou, L, Tang, HH, Zhou, XHJ, Mechelli, A, Collier, DA, Sweeney, JA, Li, T, Gong, QY (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, 196205.
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, 111117.
Morosini, PL, Magliano, L, Brambilla, L, Ugolini, S, Pioli, R (2000). Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica 101, 323329.
Navari, S, Dazzan, P (2009). Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychological Medicine 39, 17631777.
Okugawa, G, Nobuhara, K, Takase, K, Saito, Y, Yoshimura, M, Kinoshita, T (2007). Olanzapine increases grey and white matter volumes in the caudate nucleus of patients with schizophrenia. Neuropsychobiology 55, 4346.
Premkumar, P, Kumari, V, Corr, PJJ, Sharma, T (2006). Frontal lobe volumes in schizophrenia: effects of stage and duration of illness. Journal of Psychiatric Research 40, 627637.
Reeves, SJ, Grasby, PM, Howard, RJ, Bantick, RA, Asselin, MC, Mehta, MA (2005). A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition. NeuroImage 28, 216226.
Schultz, W (2007). Behavioral dopamine signals. Trends in Neurosciences 30, 203210.
Seeman, P, Kapur, S (2000). Schizophrenia: more dopamine, more D2 receptors. Proceedings of the National Academy of Sciences USA 97, 76737675.
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 152.
Shihabuddin, L, Buchsbaum, MS, Hazlett, EA, Haznedar, MM, Harvey, PD, Newman, A, Schnur, DB, Spiegel-Cohen, J, Wei, TS, Machac, J, Knesaurek, K, Vallabhajosula, S, Biren, MA, Ciaravolo, TM, Luu-Hsia, C (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.
Smieskova, R, Fusar-Poli, P, Allen, P, Bendfeldt, K, Stieglitz, RD, Drewe, J, Radue, EW, McGuire, PK, Riecher-Rossler, A, Borgwardt, SJ (2009). The effects of antipsychotics on the brain: what have we learnt from structural imaging of schizophrenia? – A systematic review. Current Pharmaceutical Design 15, 25352549.
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, 510518.
Takao, H, Abe, O, Yamasue, H, Aoki, S, Kasai, K, Ohtomo, K (2010). Cerebral asymmetry in patients with schizophrenia: a voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study. Journal of Magnetic Resonance Imagine 31, 221226.
Taylor, S, Christensen, JD, Holcomb, JM, Garver, DL (2005). Volume increases in striatum associated with positive symptom reduction in schizophrenia: a preliminary observation. Psychiatry Research Neuroimaging 140, 8589.
Toda, M, Abi-Dargham, A (2007). Dopamine hypothesis of schizophrenia: making sense of it all. Current Psychiatry Reports 9, 329336.
Tomelleri, L, Jogia, J, Perlini, C, Bellani, M, Ferro, A, Rambaldelli, G, Tansella, M, Frangou, S, Brambilla, P (2009). Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia. European Neuropsychopharmacology 19, 835840.
Volkow, ND, Gur, RC, Wang, GJ, Fowler, JS, Moberg, PJ, Ding, YS, Hitzemann, R, Smith, G, Logan, J (1998). Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. American Journal of Psychiatry 155, 344349.
Wang, HD, Dunnavant, FD, Jarman, T, Deutch, AY (2004). Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29, 12301238.
Watkins, KE, Paus, T, Lerch, JP, Zijdenbos, A, Collins, DL, Neelin, P, Taylor, J, Worsley, KJ, Evans, AC (2001). Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cerebral Cortex 11, 868877.
Woods, SW (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663667.
Yamashita, K, Yoshiura, T, Hiwatashi, A, Noguchi, T, Togao, O, Takayama, Y, Nagao, E, Kamano, H, Hatakenaka, M, Honda, H (2011). Volumetric asymmetry and differential aging effect of the human caudate nucleus in normal individuals: a prospective MR imaging study. Journal of Neuroimaging 21, 3437.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed