Polygenic Depression Risk, Neuroticism Increase Risk for Major Depressive Disorder

personality test and a pencil
personality test and a pencil
Resilience may act as a mediator between the relationship between PRS for depression and MDD.

Neuroticism and polygenic risk for depression increased the risk for major depressive disorder (MDD), whereas psychological resilience was associated with a reduced MDD risk, according to study findings published in Psychological Medicine.

Investigators examined a sample of 4166 patients from the Generation Scotland: Scottish Family Health Study to determine whether neuroticism or resilience moderated the relationship between polygenic risk scores (PRS) for MDD and clinical and self-reported depression. In addition, the researchers assessed whether the relationship between PRS for MDD and clinical and self-reported MDD was mediated by neuroticism.

In the moderation analysis, researchers found an association between PRS for depression and the increased likelihood for self-reported and clinical depression. There was no significant interaction between neuroticism and PRS or resilience and PRS. Neuroticism was found to be associated with a higher likelihood of having both clinical and self-reported depression; however, resilience correlated with a decreased risk for both.

Additionally, neuroticism mediated the relationship between PRS and clinical and self-reported depression in 2 mediation models (43%-57%). Resilience, however, mediated the relationship in the opposite direction in 2 additional mediation models (37%-40%). Neuroticism and resilience also independently mediated the genetic risk for depression for self-reported and clinical depression diagnoses.

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Because resilience was determined solely by self-report, it is possible that some patients were inappropriate for inclusion in the resilience group.

The researchers believe that resilience may act as a mediator between the relationship between PRS for depression and MDD, “by promoting habituation to stressors, encouraging efficacious coping behaviors, and prompting cognitive reappraisal away from depressive mood states.”


Navrady LB, Adams MJ, Chan SWY, et al. Genetic risk of major depressive disorder: the moderating and mediating effects of neuroticism and psychological resilience on clinical and self-reported depression [published online November 29, 2017]. Psychol Med. doi:10.1017/S0033291717003415