Polygenetic Scores Help Predict Adult Mood Disorders

Childhood polygenetic scores (PGS), along with other risk factors, could help predict adult mood disorders.

A team, led by Wonuola A. Akingbuwa, MSc, Department of Biological Psychology, Vrije University Amsterdam, examined whether genetic factors underlie the link between psychopathology and adult mood disorders and associated traits.

The meta-analysis of 7 ongoing longitudinal birth and childhood cohorts from the UK, Netherlands, Sweden, Norway, and Finland included the data from 42,998 participants.

Each participant was repeatedly assessed for childhood psychopathology from ages 6-17 and the starting points of data collection ranged from July 1985 to April 2002.

The team constructed individual polygenic scores in children based on genome-wide association studies of adults with major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI)

The investigators used regression meta-analyses to test the link between individual polygenetic scores and ADHD symptoms, as well as internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depend on childhood phenotype, age, and rater.

The investigators discovered significant links between childhood psychopathology and adult polygenic scores of major depression, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index. However, they did not find an association between childhood psychopathology and adult polygenic scores of bipolar disorder.

The polygenic scores of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042; 95% CI, 0.017—0.049). On the other hand, the associations of polygenetic scores of subjective well-being and educational attainment were negative (β, −0.026 to −0.046; 95% CI, −0.020 to −0.057).

There was no moderation of age, type of childhood phenotype, or rate with the associations and the exceptions were stronger associations between educational attainment polygenic scores and ADHD compared with internalizing problems Δβ, 0.0561; Δ95% CI, 0.0318-0.0804; ΔSE, 0.0124), and social problems (Δβ, 0.0528; Δ95% CI, 0.0282-0.0775; ΔSE, 0.0126).

This was also true for body mass index polygenic scores and ADHD and social problems (Δβ, −0.0001 Δ95% CI, −0.0102-0.0100; ΔSE, 0.0052), compared with internalizing problems (Δβ, −0.0310 Δ95% CI, −0.0456 to −0.0164; ΔSE, 0.0074).

In addition, the association between educational attainment polygenic scores and ADHD increased with age (Δβ, −0.0032; Δ 95% CI, −0.0048 to −0.0017; ΔSE, 0.0008).

Ultimately, shared genetic factors exist between childhood psychopathology traits from at least age 6 and adult depression and associated traits.

“Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood,” the authors wrote. “Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.”

Most longitudinal studies have found the onset of mood disorders in adulthood, including depression and bipolar disorder, is preceded by childhood problems, including not only internalizing problems like depression and anxiety, but also externalizing traits like ADHD and aggression.

Investigators have found in both prospective and retrospective studies, behavioral and emotional problems during childhood and adolescents are linked to other adult outcomes that are associated with adult mood disorders.

The study, “Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals,” was published online in JAMA Psychiatry.