Refining the prediction of risk for schizophrenia: Combining putative genetic and neurodevelopmental measures to predict schizophrenia-spectrum pathology

Abstract

Social anhedonia may be a promising indicator of an underlying genetic liability for schizophrenia. However, among socially anhedonic individuals, only a minority shows schizophrenia-spectrum disorders. In attempting to understand who may develop schizophrenia-spectrum disorders, researchers have hypothesized that schizophrenia may require both genetic risk and the presence of early environmental stressors (e.g., obstetric complications). "Developmental instability," which pertains to such early environmental stressors, refers to an organism's inability to buffer the effects of environmental insults on development, and has been associated with genetic risk for schizophrenia. Although one might expect developmental instability to also be elevated in individuals at psychometrically-determined risk for schizophrenia, this hypothesis has not been well-tested. This study examined two related questions using a cohort of psychometrically-identified high risk (socially anhedonic) and control 18- year-olds, and their biological mothers: First, are measures of environmental insult (i.e., developmental instability and obstetric complications) higher in individuals at presumed genetic risk for schizophrenia-spectrum disorders (i.e., socially anhedonic individuals)? Second, do measures of environmental insult interact with putative genetic risk to predict poorer functioning on measures of clinical psychopathology and neurocognitive ability? Developmental instability was studied using fingerprints, minor physical anomalies and handedness. Obstetric history was obtained from biological mothers where possible. Results showed that socially anhedonic subjects had higher rates of one DI measure (minor physical anomalies) than controls. In addition, they were more clinically impaired in terms of mood disorders and schizophrenia-spectrum personality disorders, as well as overall functioning. Minor physical anomalies were also associated with higher ratings of schizophrenia-spectrum personality disorder symptoms within social anhedonics. Finally, there was an interaction between social anhedonia status and minor physical anomalies for Schizoid Personality Disorder symptoms, with the interaction associated with greater pathology over and above the contributions of each variable separately. These results support social anhedonia as an indicator of genetic liability for schizophrenia. Moreover, they suggest that developmental instability is associated with psychometrically-measured risk for schizophrenia, as well as with clinical pathology. The interaction between social anhedonia status and minor physical anomalies is in line with previous research demonstrating an interaction between genetic risk and environmental stressors.