Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder: a high-risk prospective investigation

The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample. Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n = 94); children with a parent with a non-psychotic mental health diagnosis (n = 84); and children with a parent with no records of psychiatric hospitalization (n = 66). Variables measured included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models.