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Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment

Published online by Cambridge University Press:  28 March 2017

R. Emsley ,
L. Asmal ,
S. du Plessis ,
B. Chiliza ,
L. Phahladira  and
S. Kilian
R. Emsley*
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
L. Asmal
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
S. du Plessis
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
B. Chiliza
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
L. Phahladira
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
S. Kilian
Affiliation:
Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
*
*Address for correspondence: R. Emsley, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, 8000, Cape Town, South Africa. (Email: [email protected])
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Abstract

Background

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.

Methods

We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).

Results

Excessive cortical volume reductions were observed in patients [−4.6 (6.6)%] v. controls [−1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.

Conclusions

Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

Keywords

Brain-volumecortex-volumeschizophreniaantipsychoticflupenthixoldose-response
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 12 , September 2017 , pp. 2187 - 2196
Copyright
Copyright © Cambridge University Press 2017 

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