Identical twins concordant and discordant for schizophrenia: The roles of developmental instability and neurodevelopment in etiology

A major genetic component underlying the complex etiology of schizophrenia has been substantiated and the polygenic multifactorial threshold (PMFT) model continues to be the leading conceptual model for schizophrenia's transmission. Concordance rates among monozygotic (MZ) twin pairs around 50% indicate that epigenetic and environmental factors are also important in etiology. Evidence suggests that neurodevelopmental disturbances contribute to etiology, although integration of neurodevelopmental findings with a PMFT model remains challenging. Developmental instability, the inability of an individual to maintain its ontogenetic program in the presence of perturbations, enables the integration of neurodevelopmental processes and epigenetic explanations. The present study sought to characterize the factors contributing to concordance and discordance for schizophrenia among a rare sample of MZ twins, based upon concepts related to the PMFT model, neurodevelopmental contributors to etiology, and developmental instability.; The 23 discordant and 20 concordant twin pairs included in the present investigation were from a former study of MZ pairs concordant and discordant for schizophrenia (Torrey et al., 1994a), with newly formulated diagnostic groupings based upon recent follow-up information. Archival data sets compiled for analyses included: dermatoglyphics, minor physical anomalies, obstetric and birth measures, ratings of childhood personality, and neuroanatomical, neurological and neuropsychological measures. Few differences were detected between affected twins from discordant pairs and twins from concordant pairs. The largest differences supported increased developmental instability and more labor and delivery complications in affected discordant twins. Exploratory categorical analyses revealed considerable heterogeneity between the groups of affected twins, but suggested increased developmental instability characterized a subset of affected discordant twins. Intrapair differences among discordant pairs revealed reduced hippocampal volume, increased developmental instability, psychological maladjustment in childhood, and increased neurological and neuropsychological impairments among affected twins relative to their co-twins. Reduced hippocampal volume most accurately classified affected discordant twins. Regression analyses supported an association between developmental instability and differences in hippocampal volume within discordant pairs.; The findings from this study are discussed in the context of developmental instability as an important concept for understanding the heterogeneity of trajectories leading to the schizophrenia phenotype and as a means by which epigenetic processes in schizophrenia can be studied.