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Cortical structures and their clinical correlates in antipsychotic-naïve schizophrenia patients before and after 6 weeks of dopamine D2/3 receptor antagonist treatment

Published online by Cambridge University Press:  08 May 2018

Kasper Jessen ,
Egill Rostrup ,
Rene C.W. Mandl ,
Mette Ø. Nielsen ,
Nikolaj Bak ,
Birgitte Fagerlund ,
Birte Y. Glenthøj  and
Bjørn H. Ebdrup
Kasper Jessen*
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
Egill Rostrup
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet – Glostrup, University of Copenhagen, Glostrup, Denmark
Rene C.W. Mandl
Affiliation:
Brain Center Rudolf Magnus, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
Mette Ø. Nielsen
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
Nikolaj Bak
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
Birgitte Fagerlund
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Psychology, University of Copenhagen, Copenhagen, Denmark
Birte Y. Glenthøj
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
Bjørn H. Ebdrup
Affiliation:
Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark
*
Author for correspondence: Kasper Jessen, E-mail: kasper.jessen@regionh.dk
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Abstract

Background

Schizophrenia has been associated with changes in both cortical thickness and surface area, but antipsychotic exposure, illness progression and substance use may confound observations. In antipsychotic-naïve schizophrenia patients, we investigated cortical thickness and surface area as well as mean curvature before and after monotherapy with amisulpride, a relatively selective dopamine D2/3 receptor antagonist.

Methods

Fifty-six patients and 59 matched healthy controls (HCs) underwent T1-weighted 3T magnetic resonance imaging. Forty-one patients and 51 HCs were re-scanned. FreeSurfer-processed baseline, follow-up values and symmetrized percentage changes (SPC) in cortical structures were analysed using univariate analysis of variance. Clinical measures comprised psychopathology ratings, assessment of functioning and tests of premorbid and current intelligence. We applied false discovery rate correction to account for multiple comparisons.

Results

At baseline, groups did not differ in cortical thickness or surface area; however, curvature in the left hemisphere was higher in patients (p = 0.015). In both patients and HCs, higher curvature was associated with lower premorbid (p = 0.009) and current intelligence (p < 0.001). Lower surface area was associated with lower premorbid intelligence (p = 0.017). After 6 weeks, the cortical structures did not differ between groups. Amisulpride dose (275.0 mg/day) did not correlate with any cortical structures (p > 0.43). Cortical thickness SPC was negatively associated with symptom improvement (p = 0.002).

Conclusions

Schizophrenia appears associated with subtle, yet clinically relevant aberrations in cortical structures. Mean curvature holds promise as a sensitive supplement to cortical thickness and surface area to detect complex structural brain abnormalities.

Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 5 , April 2019 , pp. 754 - 763
Copyright
Copyright © Cambridge University Press 2018 

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