Deviant cortical sulcation related to schizophrenia, but not cognitive deficits, likely predate brain development in the second trimester

Abstract

Objectives: Aberrant cortical development, inferred from cortical folding measures, is linked to the risk of schizophrenia. Cortical folds develop in a time-locked fashion during fetal growth.We leveraged this temporal specificity of sulcation to investigate the approximate timing of the prenatal insult linked to schizophrenia as well as the cognitive impairment seen in this illness. Methods: Anatomical T1 MRI scans from a publicly available dataset of 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth. 5 major primary sulci that are invariable, representing lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, intraparietal sulcus and inferior frontal sulcus) with formation representing distinct developmental periods were chosen. Sulcal depth was measured using BrainVISA software. Results: A repeated measure Analysis of Variance with 5 sulci and 2 hemispheres as withinsubject factors and gender, age and intracranial volume as covariates revealed a significant effect of diagnosis (F[1,134]=14.8, p=0.0002). Control subjects had had deeper superior temporal (left t=3.2, p=0.002; right t=2.8, p=0.006), right inferior frontal (t=2.7, p=0.007) and left calcarine (t=2.2, p=0.03) sulci. A deeper superior frontal sulcus predicted better overall cognitive scores (F[1,54]=8.7, p=0.005) among patients. Conclusion:Our results suggest that the gestational cortical disruption underlying schizophrenia is likely to predate, if not, coincide with the appearance of calcarine sulcus (early 2 nd trimester) and affects frontal, temporal and occipital lobes. Nevertheless, the burden of cognitive deficits may relate specifically to aberrant superior frontal development occurring in late 2 nd trimester.

Longitudinal allometry of sulcal morphology in health and schizophrenia

“…Early-life neurodevelopmental processes are thought to be aberrant in first-episode psychosis (FEP) and schizophrenia (SZ). This notion is corroborated by consistently reported average reductions in the degree of folding and sulcation of FEP and SZ relative to healthy individuals (HI) (Penttilä et al, 2009;Palaniyappan et al, 2011;Janssen et al, 2014;Lavoie et al, 2014;Nanda et al, 2014;Nesvåg et al, 2014;Cachia et al, 2015;Gay et al, 2017;MacKinley et al, 2019;Dazzan et al, 2020) . However, the degree of folding is not static throughout life in HI and reduces postnatally, during adolescence, and beyond (Alemán-Gómez et al, 2013;Mutlu et al, 2013;Li et al, 2014;Cao et al, 2017) .…”