King's College London

Research portal

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number13
Issue number1
Early online date2 Mar 2022
E-pub ahead of print2 Mar 2022
Published2 Mar 2022

Bibliographical note

Funding Information: This work was funded by the Medical Research Council, UK, Grant MR/L003988/1 to A.E. and by the European Community’s Seventh Framework Programme (FP7/2007–2013), grant 279227 to J.H.M. This study presents independent research funded in part by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London, and Maudsley National Health Service (NHS) Foundation Trust and King’s College London. Funding Information: G.J.B. receives honoraria for teaching from General Electric Healthcare, who also part-fund a PhD studentship. A.A. is receiving funding from the Portuguese Foundation for Science and Technology (FCT). J.H.M. has received investigator-initiated grant support from H Lundbeck, independently of this work. O.D.H. is a part-time employee of H Lundbeck A/s. He has received investigator-initiated research funding from and/or participated in advisory/ speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Recordati, Roche and Viatris/Mylan. The remaining authors report no relevant financial interests or potential conflicts of interest. Publisher Copyright: © 2022, The Author(s).

King's Authors


The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454