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. 2013 Oct;70(10):1031-40.
doi: 10.1001/jamapsychiatry.2013.203.

Cortical folding defects as markers of poor treatment response in first-episode psychosis

Lena Palaniyappan  1 , Tiago Reis Marques, Heather Taylor, Rowena Handley, Valeria Mondelli, Stefania Bonaccorso, Annalisa Giordano, Grant McQueen, Marta DiForti, Andrew Simmons, Anthony S David, Carmine M Pariante, Robin M Murray, Paola Dazzan
Affiliations

Cortical folding defects as markers of poor treatment response in first-episode psychosis

Lena Palaniyappan et al. JAMA Psychiatry. 2013 Oct.

Abstract

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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Conflict of interest statement

Declaration of Interest:

Robin M Murray has received honoraria for lectures from Janssen, Astra-Zeneca, Lilly, Novartis, and BMS. Anthony David has received honoraria for lectures from Janssen and has served on advisory boards for Eli-Lilly and Novartis. Lena Palaniyappan received a Young Investigator travel fellowship sponsored by Eli Lilly. Rowena Handley (formerly employed by the Institute of Psychiatry) is an employee of Bristol Myers-Squibb. Drs. T.M., H.T., C.C., A.G., V.M., S.B., M.F., A.S., C.P., and P.D. report no competing interests.

Figures

Figure 1
Figure 1. Clusters showing differences in gyrification among Responders, Non-Responders and controls.
The contrast for Responders > Non responders is shown in red; Controls > Non-responders is shown in yellow; Controls > Responders is shown in purple. No clusters showed significant results in the opposite directions. All clusters are displayed on a reconstructed average white matter surface (fsaverage) and survived multiple testing using Monte-Carlo simulation with a cluster inclusion criterion of p=0.05. Left hemisphere is on the left side and right hemisphere on the right side of the image. The exact values of clusterwise probability for the clusters are presented in Table 2.
See this image and copyright information in PMC

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