Genetic liability to psychiatric disorders in early childhood : phenotypic effects and differing sensitivity to environmental influences

The large genome-wide association studies conducted during the past fifteen years have broadly increased our understanding of the genetic basis of psychiatric disorders. These studies have shown that not only are all psychiatric disorders highly polygenic, but the implicated genetic factors are largely common variation that all of us carry. This raises the question of whether the common genetic liability is also manifested in the unaffected general population, and, whether they have detectable effects, or phenotypic effects, already in childhood, suggesting genetically influenced psychopathological developmental pathways. Furthermore, the genetic factors may have indirect effects by affecting the sensitivity to the environment. Studying these effects may increase our understanding of genetically influenced developmental pathways to mental health problems, which is essential in considering preventive measures and interventions. The main aim of this thesis was to examine the effect of genetic liability for psychiatric disorders on childhood development and on the sensitivity to environmental influences in the first two years of life. The focus was on the genetic liability for two phenotypes: schizophrenia, a severe mental disorder profoundly affecting the function of neuronal networks and typically manifesting with cognitive impairments, and neuroticism, a trait associated with problems in emotion regulation and general susceptibility to mental health problems. The childhood phenotypes covered a wide range of indicators, from markers of neurophysiological maturation to motor as well as socio-emotional development. The study utilized three Finnish birth cohorts, the Northern Finland Birth Cohort 1966 (Study I), CHILD-SLEEP (Studies II and III), and FinnBrain (Study III). Additionally, a Finnish schizophrenia family sample was used as a replication sample (Study I). Polysomnography recordings analyzed in Study II were available for a subsample (N = 92) of the CHILD-SLEEP birth cohort. Motor development (Study II) and socio-emotional development measured by internalizing and externalizing symptoms (Study III) were parentally assessed and neurophysiological development was based on sleep-electroencephalogram (EEG) recordings (Study II). Additionally, we used information on schizophrenia diagnosis in adulthood (Study I). We found the genetic liabilities for schizophrenia and neuroticism to be associated with childhood development, including neurophysiological, motor, and socio-emotional development, and with sensitivity to the environment, in the first two years of life. More specifically, we found higher genetic risk for neuroticism was associated with more externalizing symptoms in two-year-old boys and higher genetic risk for schizophrenia was associated with slower motor development in eight-month-old girls. Both genetic risk scores were associated with sleep-EEG traits, although there were age-dependent differences. Genetic risk for schizophrenia was additionally associated with higher sensitivity to early environmental factors; in women, higher genetic risk together with high birthweight, reflecting pre- and perinatal environmental factors, were associated with a higher likelihood of schizophrenia diagnosis in adulthood. In conclusion, this thesis suggests that the genetic risk factors for schizophrenia and neuroticism may already have age- and developmental phase–dependent phenotypic effects in the first two years of life, partially in a gender-specific manner. However, whether this implies that the developmental process leading to an increased risk for mental health problems may already start soon after birth is not yet clear and more research, including longitudinal studies, is needed before we can fully understand the implications. Our study also suggests that genetic liability for psychiatric disorders may affect the child’s sensitivity to environmental effects. The role of the environment in shaping the influence of genetic effects on development should be considered more extensively in future studies in order to advance our understanding of the possibly harmful and protective elements of the environment – vital information in considering preventive measures and intervention.