RT Journal Article SR Electronic T1 Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness JF Journal of Psychiatry and Neuroscience JO J Psychiatry Neurosci FD Canadian Medical Association SP 125 OP 133 DO 10.1503/jpn.180144 VO 45 IS 2 A1 Vladislav Drobinin A1 Holly Van Gestel A1 Alyson Zwicker A1 Lynn MacKenzie A1 Jill Cumby A1 Victoria C. Patterson A1 Emily Howes Vallis A1 Niamh Campbell A1 Tomas Hajek A1 Carl A. Helmick A1 Matthias H. Schmidt A1 Martin Alda A1 Chris V. Bowen A1 Rudolf Uher YR 2020 UL http://jpn.ca/content/45/2/125.abstract AB 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.