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

Fanni Krajner; Laila Hadaya; Grant McQueen; Kyra-Verena Sendt; Amy Gillespie; Alessia Avila; John Lally; Emily P. Hedges; Kelly Diederen; Oliver D. Howes; Gareth J. Barker; David J. Lythgoe; Matthew J. Kempton; Philip McGuire; James H. MacCabe; Alice Egerton

doi:10.1038/s41537-022-00230-2

npj Schizophrenia (Mar 2022)

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

Fanni Krajner,
Laila Hadaya,
Grant McQueen,
Kyra-Verena Sendt,
Amy Gillespie,
Alessia Avila,
John Lally,
Emily P. Hedges,
Kelly Diederen,
Oliver D. Howes,
Gareth J. Barker,
David J. Lythgoe,
Matthew J. Kempton,
Philip McGuire,
James H. MacCabe,
Alice Egerton

Affiliations

Fanni Krajner: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Laila Hadaya: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Grant McQueen: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Kyra-Verena Sendt: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Amy Gillespie: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Alessia Avila: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
John Lally: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Emily P. Hedges: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Kelly Diederen: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Oliver D. Howes: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Gareth J. Barker: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
David J. Lythgoe: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Matthew J. Kempton: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Philip McGuire: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
James H. MacCabe: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park
Alice Egerton: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, De Crespigny Park

DOI: https://doi.org/10.1038/s41537-022-00230-2
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 8

Abstract

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Abstract 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.

Published in npj Schizophrenia

ISSN: 2334-265X (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system: Psychiatry
Website: https://www.nature.com/npjschz/

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