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Original Investigation |

Cortical Folding Defects as Markers of Poor Treatment Response in First-Episode Psychosis

Lena Palaniyappan, MRCPsych1; Tiago Reis Marques, MD2; Heather Taylor, MSc2; Rowena Handley, PhD2,6; Valeria Mondelli, MD, PhD3; Stefania Bonaccorso, MD, PhD2; Annalisa Giordano, MD2,4; Grant McQueen, BSc2; Marta DiForti, MD2; Andrew Simmons, PhD5; Anthony S. David, MD, FRCPsych2; Carmine M. Pariante, MD, MRCPsych, PhD3; Robin M. Murray, FRS, DSc2; Paola Dazzan, MD, MRCPsych, PhD2,4
[+] Author Affiliations
1Translational Neuroimaging, Division of Psychiatry, Institute of Mental Health, University of Nottingham and Nottinghamshire Healthcare National Health Service Trust, Nottingham, England
2Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, England
3Department of Psychological Medicine, Institute of Psychiatry, King’s College London, London, England
4National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust, King’s College London, London, England
5Department of Neuroimaging, Institute of Psychiatry, King’s College London, London, England
6now with Bristol-Myers Squibb
JAMA Psychiatry. 2013;70(10):1031-1040. doi:10.1001/jamapsychiatry.2013.203.
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Importance  At present, no reliable predictors exist to distinguish future responders from nonresponders to treatment during the first episode of psychosis. Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterize, already at illness onset, a subgroup of patients with particularly poor outcome.

Objective  To determine whether patients with first-episode psychosis who do not respond to 12 weeks of antipsychotic treatment already have significant gyrification defects at illness onset.

Design  Case-control study with 12 weeks’ longitudinal follow-up to determine treatment response.

Setting  Secondary psychiatric services in an inner-city area (South London, England).

Participants  A total of 126 subjects, including 80 patients presenting with first-episode psychosis and 46 healthy controls. Patients were scanned at the outset and received various antipsychotic medications in a naturalistic clinical setting. They were followed up for 12 weeks and classified as responders or nonresponders if they reached criteria for symptom remission, evaluated with the Psychiatric and Personal History Schedule.

Observation  Patients were exposed to naturalistic antipsychotic treatment for 12 weeks following a magnetic resonance imaging scan.

Main Outcomes and Measures  Cortical gyrification was assessed using local gyrification index in a vertexwise fashion across the entire cortical surface with correction for multiple testing using permutation analysis. Differences in local gyrification index were assessed between responders, nonresponders, and healthy controls. The effect of diagnosis (affective vs nonaffective psychosis) on the local gyrification index was also investigated in responders and nonresponders.

Results  Patients with first-episode psychosis showed a significant reduction in gyrification (hypogyria) across multiple brain regions compared with healthy controls. Interestingly, nonresponders showed prominent hypogyria at bilateral insular, left frontal, and right temporal regions when compared with responders (all clusters significant at P < .05). These effects were present for both affective and nonaffective psychoses.

Conclusions and Relevance  Gyrification appears to be a useful predictor of antipsychotic treatment response. Early neurodevelopmental aberrations may predict unfavorable prognosis in psychosis, irrespective of the existing diagnostic boundaries.

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Figure.
Clusters Showing Differences in Gyrification Among Responders, Nonresponders, and Controls

No clusters showed significant results in the opposite directions to the contrasts shown in the Figure. All clusters are displayed on a reconstructed average white matter surface (fsaverage in FreeSurfer software) and survived multiple testing using Monte-Carlo simulation with a cluster inclusion criterion of P = .05. The left hemisphere is on the left side of the image, and the right hemisphere is on the right side. The exact values of clusterwise probability for the clusters are presented in Table 2.

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