Abstract
ObjectivesAberrant 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.MethodsAnatomical 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.ResultsA 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.ConclusionOur 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.
Highlights
An emerging body of evidence implicates aberrations in fetal cortical development to cognitive and mental health outcomes later in life [1,2]
Our results suggest that the gestational disruption underlying schizophrenia is likely to predate, if not coincide with the appearance of calcarine sulcus
The ANOVA showed a significant between-subject effect for diagnosis (F[1,134] = 14.8, p = 0.0002), with significant effects identified for gender (F[1,134] = 7.4, p = 0.007, sulcal depth for females > males) and age (F[1,134] = 4.5, p = 0.035; reduced depth with increasing age)
Summary
An emerging body of evidence implicates aberrations in fetal cortical development to cognitive and mental health outcomes later in life [1,2]. The primary sulci of the human brain follow a course of programmed progressive development that occurs in a time-locked fashion and is highly sensitive to fetal disruptions [1]. The development of the primary sulci defining lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, intraparietal sulcus and inferior frontal sulcus) is so precise in the developing fetuses (with emergence at 16, 23, 25, 26 and 28 weeks, respectively [1]) that these structures can be used to estimate gestational age and brain maturation [2]. Studying the location of aberrations in cortical folding in adult life can serve as a window to the time-locked disruptions suffered by the developing cortical architecture [3]
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