Shared genetic influences between depression and conduct disorder in children and adolescents: A systematic review.

INTRODUCTION: The co-occurrence between major depression disorder (MDD) and conduct disorder (CD) is common across development and represents a significant risk factor for future psychiatric problems and long-term impairment. Large-scale quantitative genetic studies suggest that the MDD-CD co-occurrence may be partly explained by shared genetic vulnerability factors, in line with transdiagnostic models of psychopathology, but no systematic synthesis of the literature is currently available. METHODS: We therefore conducted a systematic review of the available genetic literature on the co-occurrence between MDD and CD in children and adolescents. We identified 10 eligible studies, including 5 cross-sectional bivariate/multivariate twin studies, 3 longitudinal bivariate/multivariate twin studies, and 2 latent profile/trajectory twin studies. RESULTS: Most of the reviewed studies found a strong contribution of shared genetic factors on the covariation between depression and conduct problems, in line with the prominent effect of a common genetic liability across development. LIMITATIONS: The scientific literature on this psychiatric comorbidity is still limited, as it solely consists of twin studies from high income countries. CONCLUSION: Considering the joint burden of MDD and CD on youth, families and society worldwide, future studies are needed to better investigate the shared risk processes of these frequently co-occurring conditions, in order to inform new treatments through personalized medicine.

Genome-wide DNA methylation patterns associated with general psychopathology in children.

Psychiatric symptoms are interrelated and found to be largely captured by a general psychopathology factor (GPF). Although epigenetic mechanisms, such as DNA methylation (DNAm), have been linked to individual psychiatric outcomes, associations with GPF remain unclear. Using data from 440 children aged 10 years participating in the Generation R Study, we examined the associations of DNAm with both general and specific (internalizing, externalizing) factors of psychopathology. Genome-wide DNAm levels, measured in peripheral blood using the Illumina 450K array, were clustered into wider co-methylation networks ('modules') using a weighted gene co-expression network analysis. One co-methylated module associated with GPF after multiple testing correction, while none associated with the specific factors. This module comprised of 218 CpG probes, of which 198 mapped onto different genes. The CpG most strongly driving the association with GPF was annotated to FZD1, a gene that has been implicated in schizophrenia and wider neurological processes. Associations between the probes contained in the co-methylated module and GPF were supported in an independent sample of children from the Avon Longitudinal Study of Parents and Children (ALSPAC), as evidenced by significant correlations in effect sizes. These findings might contribute to improving our understanding of dynamic molecular processes underlying complex psychiatric phenotypes.