From bench to bedside: Translating new research from genetics and neuroimaging into treatment development for early-onset schizophrenia

Objective: Children and adolescents with schizophrenia share a similar pattern of phenomenological, genetic and cognitive abnormalities to adults with schizophrenia. However, an early-onset of schizophrenia (EOS) (prior to 18 years of age) is associated with a higher frequency of risk indicators associated with schizophrenia (e.g. developmental delays and familial spectrum disorders) and a worse long-term outcome. This overview examines recent research on the neurobiological alterations, possible causes, developmental trajectory and treatment of EOS and attempts to identify gaps in the field. Method: The authors provide a selective review of major findings from genetics, neuroimaging and treatment studies of pediatric schizophrenia that were presented at a workshop sponsored by the National Institute of Mental Health. These data are synthesized in conjunction with preclinical studies into a model of the pathophysiology of EOS. Results: EOS is associated with a high frequency of cytogenetic abnormalities (e.g. velocardiofacial syndrome, sex chromosome anomalies) and other rare denovo chromosomal aberrations. Brain imaging research in adolescents with EOS has revealed a progressive loss of cortical grey matter post-onset of psychosis and subtle abnormalities in white matter microstructure. Although EOS patients are more likely to be treatment-refractory than their adult counterparts, there are substantial data that this subgroup is particularly responsive to clozapine. Conclusions: Genetic or environmental factors operating during adolescence that reduce frontal capacity might contribute to an EOS in susceptible individuals. Additional longitudinal studies of adolescents with schizophrenia are needed to better understand the relationship between structural changes in fronto-limbic regions, stress responsivity, and cognitive and neurochemical development.