Skip to main content
    • Aa
    • Aa

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)...

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? *



Altmetric attention score

Full text views

Total number of HTML views: 2
Total number of PDF views: 36 *
Loading metrics...

Abstract views

Total abstract views: 317 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 26th June 2017. This data will be updated every 24 hours.