Internalizing and Externalizing Traits During Adolescence: Using Epigenetics and Perinatal Risks to Differentiate Clusters of Symptoms

This cross-sectional study aims to identify clusters of internalizing and externalizing traits during adolescence using a bottom-up approach. The second aim is to investigate whether the different clusters differ by environmental risk factors and specific epigenetic profiles. A total of 205 adolescents, who had been referred for psychopathology in childhood, were recruited. Behavioral problems were assessed using the Child Behavior Checklist/6–18 (CBCL). Different clusters of psychopathological profiles were analyzed using a Finite mixture model. Differences in environmental risk factors and epigenetic profiles were tested with χ2-tests and Bonferroni-corrected t-tests. Two clusters were identified: a LOW cluster (51% of the sample), characterized by the presence of subclinical mean scores in both internalizing and externalizing problems, and a HIGH cluster (49% of the sample), characterized by high mean scores in both domains. The HIGH cluster had a significantly greater number of perinatal complications and changes in methylation of specific CpG sites of Brain-derived neurotrophic factor, Insulin-like growth factor-2, and Oxytocin receptor, whereas no difference was found for FK506-binding protein 5. Our results confirm the existence of a strong association between early adverse events, DNA methylation, and the presence of behavioral problems and psychopathological traits in adolescence.