Expanding the schizophrenia phenotype: a composite evaluation of neurodevelopmental markers

Minor physical anomalies (MPAs) and neurologic soft signs (NSSs) have been consistently reported to be more frequent in schizophrenia subjects and their first-degree relatives. We aimed at coassessing both these neurodevelopmental markers in neuroleptic-naive recent-onset schizophrenia (NRS) subjects in comparison to healthy control (HC) subjects to explore the predictive validity of this composite endophenotype. We administered the Modified Waldrop Scale (MWS) and the Neurological Evaluation Scale (NES) to evaluate MPAs and NSSs, respectively, in 40 NRS and 30 matched HC subjects. Schizophrenia subjects had significantly higher frequencies of MPAs and NSSs than HC. Minor physical anomaly total scores were correlated with greater severity of illness, whereas NES scores did not show any relationship with clinical variables. Schizophrenia and HC subjects were most accurately classified (82.9%) when MPAs and NSSs were considered as a composite phenotype rather than independently. Minor physical anomalies and NSSs constitute independent neurodevelopmental markers of schizophrenia and would afford greater predictive validity when used as a composite endophenotype in genetic association studies.