Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development

Background Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. Methods We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. Results We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology ( p = 0.041) as well as interactions between NSS and ACC morphology ( p = 0.005), between NSS and handedness ( p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume ( p = 0.005) on CC measured using the TMT-B score – the TMT-A score. Limitations No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis. Conclusion To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.