Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 24
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Bakker, G. Caan, M. W. A. Schluter, R. S. Bloemen, O. J. N da Silva- Alves, F. de Koning, M. B. Boot, E. Vingerhoets, W. A. M. Nieman, D. H. de Haan, L. Booij, J. and van Amelsvoort, T. A. M. J. 2016. Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis. Psychological Medicine, Vol. 46, Issue. 11, p. 2299.

    Domen, Patrick Peeters, Sanne Michielse, Stijn Gronenschild, Ed Viechtbauer, Wolfgang Roebroeck, Alard Os, Jim van and Marcelis, Machteld 2016. Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study. Schizophrenia Bulletin, p. sbw061.

    Hadley, Jennifer Ann Kraguljac, Nina Vanessa White, David Matthew Ver Hoef, Lawrence Tabora, Janell and Lahti, Adrienne Carol 2016. Change in brain network topology as a function of treatment response in schizophrenia: a longitudinal resting-state fMRI study using graph theory. npj Schizophrenia, Vol. 2, p. 16014.

    Hu, M. Zong, X. Zheng, J. Mann, J. J. Li, Z. Pantazatos, S. P. Li, Y. Liao, Y. He, Y. Zhou, J. Sang, D. Zhao, H. Tang, J. Chen, H. Lv, L. and Chen, X. 2016. Risperidone-induced topological alterations of anatomical brain network in first-episode drug-naive schizophrenia patients: a longitudinal diffusion tensor imaging study. Psychological Medicine, Vol. 46, Issue. 12, p. 2549.

    Karlsgodt, Katherine H. 2016. Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol. 1, Issue. 3, p. 209.

    Kraguljac, Nina Vanessa White, David Matthew Hadley, Nathan Hadley, Jennifer Ann ver Hoef, Lawrence Davis, Ebony and Lahti, Adrienne Carol 2016. Aberrant Hippocampal Connectivity in Unmedicated Patients With Schizophrenia and Effects of Antipsychotic Medication: A Longitudinal Resting State Functional MRI Study. Schizophrenia Bulletin, Vol. 42, Issue. 4, p. 1046.

    Sun, Yueji Zhang, Liang Ancharaz, S Shasheekant Cheng, Sijian Sun, Wenheng Wang, Hongjun and Sun, Yan 2016. Decreased fractional anisotropy values in two clusters of white matter in patients with schizotypal personality disorder: A DTI study. Behavioural Brain Research, Vol. 310, p. 68.

    Uhlmann, Anne Fouche, Jean-Paul Lederer, Katharina Meintjes, Ernesta M. Wilson, Don and Stein, Dan J. 2016. White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis. Human Brain Mapping, Vol. 37, Issue. 6, p. 2055.

    Zeng, Botao Ardekani, Babak A. Tang, Yingying Zhang, Tianhong Zhao, Shanshan Cui, Huiru Fan, Xiaoduo Zhuo, Kaiming Li, Chunbo Xu, Yifeng Goff, Donald C. and Wang, Jijun 2016. Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment. Schizophrenia Research, Vol. 172, Issue. 1-3, p. 1.

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

    Alvarado-Alanis, Patricia León-Ortiz, Pablo Reyes-Madrigal, Francisco Favila, Rafael Rodríguez-Mayoral, Oscar Nicolini, Humberto Azcárraga, Mariana Graff-Guerrero, Ariel Rowland, Laura M. and de la Fuente-Sandoval, Camilo 2015. Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis. Schizophrenia Research, Vol. 162, Issue. 1-3, p. 14.

    Canu, Elisa Agosta, Federica and Filippi, Massimo 2015. A selective review of structural connectivity abnormalities of schizophrenic patients at different stages of the disease. Schizophrenia Research, Vol. 161, Issue. 1, p. 19.

    Caprihan, Arvind Jones, Thomas Chen, Hongji Lemke, Nicholas Abbott, Christopher Qualls, Clifford Canive, Jose Gasparovic, Charles and Bustillo, Juan R 2015. The Paradoxical Relationship between White Matter, Psychopathology and Cognition in Schizophrenia: A Diffusion Tensor and Proton Spectroscopic Imaging Study. Neuropsychopharmacology, Vol. 40, Issue. 9, p. 2248.

    Hutcheson, Nathan L. Sreenivasan, Karthik R. Deshpande, Gopikrishna Reid, Meredith A. Hadley, Jennifer White, David M. Ver Hoef, Lawrence and Lahti, Adrienne C. 2015. Effective connectivity during episodic memory retrieval in schizophrenia participants before and after antipsychotic medication. Human Brain Mapping, Vol. 36, Issue. 4, p. 1442.

    Kahn, R S and Sommer, I E 2015. The neurobiology and treatment of first-episode schizophrenia. Molecular Psychiatry, Vol. 20, Issue. 1, p. 84.

    Lei, Wei Li, Na Deng, Wei Li, Mingli Huang, Chaohua Ma, Xiaohong Wang, Qiang Guo, Wanjun Li, Yinfei Jiang, Lijun Zhou, Yi Hu, Xun Mary McAlonan, Grainne and Li, Tao 2015. White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study. Scientific Reports, Vol. 5, p. 12994.

    Li, Q Leung, Y O Zhou, I Ho, L C Kong, W Basil, P Wei, R Lam, S Zhang, X Law, A C K Chua, S E Sham, P C Wu, E X and McAlonan, G M 2015. Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model. Translational Psychiatry, Vol. 5, Issue. 9, p. e641.

    Prasad, Konasale M. Upton, Catherine H. Schirda, Claudiu S. Nimgaonkar, Vishwajit L. and Keshavan, Matcheri S. 2015. White matter diffusivity and microarchitecture among schizophrenia subjects and first-degree relatives. Schizophrenia Research, Vol. 161, Issue. 1, p. 70.

    White, T. Langen, C. Schmidt, M. Hough, M. and James, A. 2015. Comparative neuropsychiatry: White matter abnormalities in children and adolescents with schizophrenia, bipolar affective disorder, and obsessive-compulsive disorder. European Psychiatry, Vol. 30, Issue. 2, p. 205.

    Chiapponi, Chiara Piras, Fabrizio Fagioli, Sabrina Girardi, Paolo Caltagirone, Carlo and Spalletta, Gianfranco 2014. Hippocampus age-related microstructural changes in schizophrenia: A case–control mean diffusivity study. Schizophrenia Research, Vol. 157, Issue. 1-3, p. 214.


White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

  • Q. Wang (a1) (a2), C. Cheung (a3), W. Deng (a1) (a2), M. Li (a1), C. Huang (a1), X. Ma (a1) (a2), Y. Wang (a1) (a2), L. Jiang (a1), P. C. Sham (a3), D. A. Collier (a4), Q. Gong (a5), S. E. Chua (a3), G. M. McAlonan (a6) and T. Li (a1) (a2)
  • DOI:
  • Published online: 27 February 2013

It is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.


Thirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.


Compared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.


During the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

Corresponding author
*Author for correspondence: Professor T. Li, Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. (Email: [T. Li] (Email: [G. McAlonan]
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.

M Annett (1970). A classification of hand preference by association analysis. British Journal of Psychology 61, 303321.

BA Ardekani , J Nierenberg , MJ Hoptman , DC Javitt , KO Lim (2003). MRI study of white matter diffusion anisotropy in schizophrenia. Neuroreport 14, 20252029.

E Bora , A Fornito , J Radua , M Walterfang , M Seal , SJ Wood , M Yucel , D Velakoulis , C Pantelis (2011). Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophrenia Research 127, 4657.

W Cahn , M Rais , FP Stigter , NE van Haren , E Caspers , HE Hulshoff Pol , Z Xu , HG Schnack , RS Kahn (2009). Psychosis and brain volume changes during the first five years of schizophrenia. European Neuropsychopharmacology 19, 147151.

JH Callicott , VS Mattay , BA Verchinski , S Marenco , MF Egan , DR Weinberger (2003). Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry 160, 22092215.

A Carlsson , M Lindqvist (1963). Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica 20, 140144.

RC Chan , X Di , GM McAlonan , QY Gong (2011). Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophrenia Bulletin 37, 177188.

MY Deng , GM McAlonan , C Cheung , CP Chiu , CW Law , V Cheung , PC Sham , EY Chen , SE Chua (2009). A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naive, newly diagnosed schizophrenia. Psychopharmacology 206, 437446.

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.

A Federspiel , S Begre , C Kiefer , G Schroth , WK Strik , T Dierks (2006). Alterations of white matter connectivity in first episode schizophrenia. Neurobiology of Disease 22, 702709.

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.

BC Ho , NC Andreasen , S Ziebell , R Pierson , V Magnotta (2011). Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry 68, 128137.

BC Ho , P Milev , DS O'Leary , A Librant , NC Andreasen , TH Wassink (2006). Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Archives of General Psychiatry 63, 731740.

CE Hugenschmidt , AM Peiffer , RA Kraft , R Casanova , AR Deibler , JH Burdette , JA Maldjian , PJ Laurienti (2008). Relating imaging indices of white matter integrity and volume in healthy older adults. Cerebral Cortex 18, 433442.

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.

R Kanaan , G Barker , M Brammer , V Giampietro , S Shergill , J Woolley , M Picchioni , T Toulopoulou , P McGuire (2009 a). White matter microstructure in schizophrenia: effects of disorder, duration and medication. British Journal of Psychiatry 194, 236242.

RA Kanaan , S Borgwardt , PK McGuire , MC Craig , DG Murphy , M Picchioni , SS Shergill , DK Jones , M Catani (2009 b). Microstructural organization of cerebellar tracts in schizophrenia. Biological Psychiatry 66, 10671069.

RA Kanaan , SS Shergill , GJ Barker , M Catani , VW Ng , R Howard , PK McGuire , DK Jones (2006). Tract-specific anisotropy measurements in diffusion tensor imaging. Psychiatry Research 146, 7382.

SR Kay , A Fiszbein , LA Opler (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.

GT Konopaske , KA Dorph-Petersen , JN Pierri , Q Wu , AR Sampson , DA Lewis (2007). Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology 32, 12161223.

GT Konopaske , KA Dorph-Petersen , RA Sweet , JN Pierri , W Zhang , AR Sampson , DA Lewis (2008). Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biological Psychiatry 63, 759765.

N Koutsouleris , C Gaser , R Bottlender , C Davatzikos , P Decker , M Jager , G Schmitt , M Reiser , HJ Moller , EM Meisenzahl (2010). Use of neuroanatomical pattern regression to predict the structural brain dynamics of vulnerability and transition to psychosis. Schizophrenia Research 123, 175187.

M Kubicki , CF Westin , PG Nestor , CG Wible , M Frumin , SE Maier , R Kikinis , FA Jolesz , RW McCarley , ME Shenton (2003). Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biological Psychiatry 54, 11711180.

M Leung , C Cheung , K Yu , B Yip , P Sham , Q Li , S Chua , G McAlonan (2011). Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting. Schizophrenia Bulletin 37, 199211.

DA Lewis (2011). Antipsychotic medications and brain volume: do we have cause for concern? Archives of General Psychiatry 68, 126127.

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.

S Lui , W Deng , X Huang , L Jiang , X Ma , H Chen , T Zhang , X Li , D Li , L Zou , H Tang , XJ Zhou , A Mechelli , DA Collier , JA Sweeney , T Li , Q Gong (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.

S Lui , T Li , W Deng , L Jiang , Q Wu , H Tang , Q Yue , X Huang , RC Chan , DA Collier , SA Meda , G Pearlson , A Mechelli , JA Sweeney , Q Gong (2010). Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by ‘resting state’ functional magnetic resonance imaging. Archives of General Psychiatry 67, 783792.

L McCormick , L Decker , P Nopoulos , BC Ho , N Andreasen (2005). Effects of atypical and typical neuroleptics on anterior cingulate volume in schizophrenia. Schizophrenia Research 80, 7384.

B Olabi , I Ellison-Wright , AM McIntosh , SJ Wood , E Bullmore , SM Lawrie (2011). Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biological Psychiatry 70, 8896.

BD Peters , J Blaas , L de Haan (2010). Diffusion tensor imaging in the early phase of schizophrenia: what have we learned? Journal of Psychiatry Research 44, 9931004.

BD Peters , L de Haan , N Dekker , J Blaas , HE Becker , PM Dingemans , EM Akkerman , CB Majoie , T van Amelsvoort , GJ den Heeten , DH Linszen (2008). White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis. Neuropsychobiology 58, 1928.

BD Peters , N Schmitz , PM Dingemans , TA van Amelsvoort , DH Linszen , L de Haan , CB Majoie , GJ den Heeten (2009). Preliminary evidence for reduced frontal white matter integrity in subjects at ultra-high-risk for psychosis. Schizophrenia Research 111, 192193.

G Rosenberger , M Kubicki , PG Nestor , E Connor , GB Bushell , D Markant , M Niznikiewicz , CF Westin , R Kikinis , AJ Saykin , RW McCarley , ME Shenton (2008). Age-related deficits in fronto-temporal connections in schizophrenia: a diffusion tensor imaging study. Schizophrenia Research 102, 181188.

M Pressler , P Nopoulos , BC Ho , NC Andreasen (2005). Insular cortex abnormalities in schizophrenia: relationship to symptoms and typical neuroleptic exposure. Biological Psychiatry 57, 394398.

D Segal , JR Koschnick , LH Slegers , PR Hof (2007). Oligodendrocyte pathophysiology: a new view of schizophrenia. International Journal of Neuropsychopharmacology 10, 503511.

KE Stephan , T Baldeweg , KJ Friston (2006). Synaptic plasticity and dysconnection in schizophrenia. Biological Psychiatry 59, 929939.

NE van Haren , HE Hulshoff Pol , HG Schnack , W Cahn , RC Mandl , DL Collins , AC Evans , RS Kahn (2007). Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology 32, 20572066.

AC Vernon , S Natesan , M Modo , S Kapur (2011). Effect of chronic antipsychotic treatment on brain structure: a serial magnetic resonance imaging study with ex vivo and postmortem confirmation. Biological Psychiatry 69, 936944.

F Wang , Z Sun , L Cui , X Du , X Wang , H Zhang , Z Cong , N Hong , D Zhang (2004). Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging. American Journal of Psychiatry 161, 573575.

T White , VA Magnotta , HJ Bockholt , S Williams , S Wallace , S Ehrlich , BA Mueller , BC Ho , RE Jung , VP Clark , J Lauriello , JR Bustillo , SC Schulz , RL Gollub , NC Andreasen , VD Calhoun , KO Lim (2011). Global white matter abnormalities in schizophrenia: a multisite diffusion tensor imaging study. Schizophrenia Bulletin 37, 222232.

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? *