Polygenic Risk Scores May Predict Depression Outcomes in Youth

Depression polygenic risk score may support the identification of youths at risk for major depression before the emergence of clinically significant symptoms.

Depression polygenic risk scores (PRSs) and exposure to childhood abuse may predict depression onset and severity in youths, according to a study published in the American Journal of Psychiatry.

Investigators assessed the predictive validity of depression PRSs for depressive symptoms in clinical and epidemiological youth cohorts. The PRS for the present study was derived from a prior genome-wide association study in adults. The clinical cohort comprised 279 youths with major depression (mean age, 14.76±2.00 years; 68% girls) and 187 healthy control subjects (mean age, 14.67±2.45 years; 63% girls). Depression was assessed in the clinical cohort, using the Beck Depression Inventory; exposure to childhood abuse was captured via self-report.

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Two epidemiological cohorts were used. The first included 1450 youths (mean age, 13.99±0.92 years; 63% girls), and the second comprised children assessed at ages 8 (n=184; 49.2% girls) and 11 (n=317; 46.7% girls) years. Individuals in the first epidemiological cohort who did not report depression at baseline (n=694) underwent follow-up assessments at 6, 12, and 24 months. The Children’s Depression Inventory and the Childhood Trauma Questionnaire were used to assess depressive symptoms and childhood abuse, respectively, in this cohort. The second epidemiological cohort was used as a replication set; participants documented depression with the Child Behavior Checklist.

Participants were genotyped using blood and buccal samples; multivariate regression models were used to assess the relationships among depression PRS, childhood abuse, and each outcome.

In the clinical cohort, higher depression PRSs were observed in case subjects relative to control subjects (odds ratio, 1.560; 95% CI, 1.230-1.980; corrected P =.001). A positive relationship was observed between depressive symptom severity and depression PRS (corrected P =.010). In addition, case subjects with an earlier age at onset had a higher depression PRS than those with later onset (corrected P =.036).

In the first epidemiological cohort, depression PRS predicted baseline depression symptoms (corrected P =.012) and prospectively predicted onset of moderate to severe depressive symptoms within the next 2 years (hazard ratio, 1.202; 95% CI, 1.045-1.383; corrected P =.020). These associations were replicated in the second epidemiological cohort. In the additive model, both depression PRS (hazard ratio, 1.171; 95% CI, 1.016-1.350; corrected P =.039) and exposure to childhood abuse (hazard ratio, 2.817; 95% CI, 1.963-4.043; corrected P =.00006750) significantly predicted the onset of moderate to severe depressive symptoms or a clinical diagnosis of major depression. No interactive effect was observed between depression PRS and childhood abuse on depression outcomes.

Per these data, depression PRSs derived from adults have validity as an early indicator of depression in youths. Additional research with a larger clinical cohort is necessary to confirm these findings.


Halldorsdottir T, Piechaczek C, Soares de Matos AP, et al. Polygenic risk: predicting depression outcomes in clinical and epidemiological cohorts of youths [published online April 5, 2019]. Am J Psychiatry. doi:10.1176/appi.ajp.2019.18091014