Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness

Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness

J Psychiatry Neurosci 2020;45(2):125-133 | PDF | Appendix

Vladislav Drobinin, BSc; Holly Van Gestel, MSc; Alyson Zwicker, PhD; Lynn MacKenzie, PhD; Jill Cumby, MN; Victoria C. Patterson, BA; Emily Howes Vallis, MSc; Niamh Campbell, BSc; Tomas Hajek, MD, PhD; Carl A. Helmick, BSC; Matthias H. Schmidt, MSc, MD; Martin Alda, MD; Chris V. Bowen, PhD; Rudolf Uher, MD, PhD

Background: Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms.

Methods: We collected MRIs and examined the local gyrification index in a sample of 110 youth (mean age ± standard deviation 14.0 ± 3.7 yr; range 9–25 yr) with a family history of severe mental illness: 48 with psychotic symptoms and 62 without. Images were processed using the Human Connectome Pipeline and FreeSurfer. We tested for group differences in local gyrification index using mixed-effects generalized linear models controlling for age, sex and familial clustering. Sensitivity analysis further controlled for intracranial volume, IQ, and stimulant and cannabis use.

Results: Youth with psychotic symptoms displayed an overall trend toward lower cortical folding across all brain regions. After adjusting for multiple comparisons and confounders, regional reductions were localized to the frontal and occipital lobes. Specifically, the medial (B = –0.42, pFDR = 0.04) and lateral (B = –0.39, pFDR = 0.04) orbitofrontal cortices as well as the cuneus (B = –0.47, pFDR = 0.03) and the pericalcarine (B = –0.45, pFDR = 0.03) and lingual (B = –0.38, pFDR = 0.04) gyri.

Limitations: Inference about developmental trajectories was limited by the cross-sectional data.

Conclusion: Psychotic symptoms in youth are associated with cortical folding deficits, even in the absence of psychotic illness. The current study helps clarify the neurodevelopmental basis of psychosis at an early stage, before medication, drug use and other confounds have had a persistent effect on the brain.


Submitted Aug. 21, 2018; Revised Jun. 17, 2019; Accepted Jul. 3, 2019; Published online Nov. 1, 2019

Acknowledgements: This project was supported by the Independent Investigator Award, Brain & Behavior Research Foundation (R. Uher; grant number 24684), the Canada Research Chairs Program (award number 231397), the Canadian Institutes of Health Research (grant reference numbers 124976, 142738 and 148394), the Nova Scotia Health Authority and the Dalhousie Medical Research Foundation. V. Drobinin was supported by the Canadian Institutes of Health Research doctoral award (157975). The Biomedical Translational Imaging Centre (BIOTIC) has received funding support from Brain Canada.

Affiliations: From the Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada (Drobinin, Schmidt, Uher); the Nova Scotia Health Authority, Halifax, NS (Drobinin, van Gestel, Zwicker, MacKenzie, Cumby, Patterson, Vallis, Campbell, Helmick, Alda, Bowen, Uher); the Department of Pathology, Dalhousie University, Halifax, NS (Zwicker, Uher); the Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS (MacKenzie, Patterson, Uher); the Department of Psychiatry, Dalhousie University, Halifax, NS (Vallis, Helmick, Alda, Uher); the Department of Medicine, Dalhousie University, Halifax, NS (Campbell); and the Department of Diagnostic Radiology, Dalhousie University, Halifax, NS (Bowen).

Competing interests: None declared.

Contributors: V. Drobinin, M. Schmidt, M. Alda, C. Bowen and R. Uher designed the study. V. Drobinin, H. van Gestel, A. Zwicker, L. MacKenzie, J. Cumby, V. Patterson, E. Howes Vallis, N. Campbell, T. Hajek, C. Helmick and R. Uher acquired the data, which V. Drobinin and R. Uher analyzed. V. Drobinin wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.180144

Correspondence to: V. Drobinin, 13E, 5850 College St., Halifax, NS, B3H 4H7; vlad.drobinin@dal.ca