Brain Disorders and InjuryDevelopmentJournalLanguage and Communication

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, Nless than or equal to5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.

The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but which exert their maximum influence during different periods of development”, explained Beate St Pourcain, senior investigator at the MPI and lead author of the study.

St Pourcain, B., Robinson, E. B., Anttila, V., Sullivan, B. B., Maller, J., Golding, J., Skuse, D., Ring, S., Evans, D. M., Zammit, S., Fisher, S. E., Neale, B. M., Anney, R., Ripke, S., Hollegaard, M. V., Werge, T., iPSYCH-SSI-Broad Autism Group, Ronald, A., Grove, J., Hougaard, D. M., Børglum, A. D., Mortensen, P. B., Daly, M., & Davey Smith, G. (2017). ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social-communication difficulties. Molecular Psychiatry. Advance online publication.