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

Abstract

ObjectivesAberrant 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. MethodsAnatomical 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. ResultsA repeated measure Analysis of Variance with 5 sulci and 2 hemispheres as within-subject 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. ConclusionOur results suggest that the gestational cortical disruption underlying schizophrenia is likely to predate, if not, coincide with the appearance of calcarine sulcus (early 2nd 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 2nd trimester.