Deviant cortical sulcation related to schizophrenia and cognitive deficits in the second trimester

Aberrant cortical development, inferred from cortical folding, 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 timing of the prenatal insult linked to schizophrenia and the cognitive impairment seen in this illness. Anatomical MRI scans from 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth of five major invariable primary sulci representing lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, intraparietal sulcus and inferior frontal sulcus) with formation representing the distinct developmental periods. A repeated-measure ANOVA with five sulci and two hemispheres as the 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 deeper bilateral superior temporal, right inferior frontal and left calcarine sulci. A deeper superior frontal sulcus predicted better cognitive scores among patients. Our results suggest that the gestational disruption underlying schizophrenia is likely to predate, if not coincide with the appearance of calcarine sulcus (early second trimester). Nevertheless, the burden of cognitive deficits may relate specifically to the aberrant superior frontal development apparent in late second trimester