Meta-analysis reveals shared genetic factors between childhood psychopathology, adult depression

Childhood psychopathology traits starting at age 6 years and adult depression and its associated traits share genetic factors, according to results of a meta-analysis published in JAMA Psychiatry.

“Longitudinal studies indicate that the onset of mood disorders in adulthood, including depression and bipolar disorder, is often preceded by childhood problems,” Wonuola A. Akingbuwa, MSc, of the department of biological psychology at Vrije University Amsterdam, and colleagues wrote. “These include not only internalizing problems, such as depression and anxiety, but also externalizing traits, such as [ADHD] and aggression. Moreover, both in prospective and retrospective studies, behavioral and emotional problems during childhood and adolescence have been associated with other adult outcomes that are associated with adult mood disorders, including educational attainment, insomnia, subjective well-being, personality, and [BMI].”

Molecular genetic and twin/family studies reported heritability and stability of psychopathology over time. Further, studies among families at high risk for bipolar disorder showed that children whose parents had bipolar disorder were susceptible to psychiatric disorders and symptoms in childhood, adolescence and early adulthood. According to Akingbuwa and colleagues, these results suggest “genetic factors may underlie the persistence of symptoms or the transition from one disorder to another between childhood and adulthood.”

In the current meta-analysis, the investigators aimed to determine whether genetic risk for adult mood disorders and associated traits is linked to childhood disorders. They examined data from seven ongoing longitudinal birth and childhood cohorts from the U.K., the Netherlands, Sweden, Norway and Finland, with data collection starting points ranging from July 1985 to April 2002. Using data from genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment and BMI, the researchers constructed individual polygenic scores in children. They also conducted regression meta-analyses to determine associations between polygenic scores and ADHD symptoms and internalizing and social problems measured repeatedly across childhood and adolescence, as well as whether these associations depended on childhood phenotype, age and rater.

The study included 42,998 participants aged 6 years to 17 years. The proportion of male participants varied from 43% to 53.1% by age and across all cohorts. Results showed a positive association between polygenic scores of adult major depression, neuroticism, BMI and insomnia and childhood psychopathology (beta estimate range = 0.023-0.042; 95% CI, 0.017-0.049). The researchers reported negative associations between childhood psychopathology and polygenic scores of subjective well-being and educational attainment (beta = 0.026 to 0.046; 95% CI, 0.02 to 0.057). Further, they found no moderation of age, type of childhood phenotype or rater with the associations. However, exceptions included stronger associations between educational attainment polygenic score and ADHD compared with internalizing problems and social problems, and between BMI polygenic score and ADHD and social problems, compared with internalizing problems. Moreover, the association between educational attainment polygenic score and ADHD increased with age.

“We demonstrate the power of combining genetic longitudinal population data to elucidate developmental patterns in psychopathology,” the researchers wrote. “Our study provides novel evidence for the presence of shared genetic factors between childhood psychopathology and depression and associated adult traits, as well as their stability across development. Insight into these associations may aid identification of children at risk for a relatively chronic course of illness, ultimately facilitating targeted treatment to this vulnerable group.” – by Joe Gramigna

Disclosures: Akingbuwa reports grants from the Biobanking and Biomolecular Resources Research Infrastructure European Research Council, European Union FP7, European Union Horizon 2020 research and innovation program, Netherlands Organization for Health Research and Development, Netherlands Organization for Scientific Research, the NIH and the NIMH. Please see the study for all other authors’ relevant financial disclosures.