title: Polygenic phenotypic plasticity moderates the effects of severe childhood abuse on depressive symptom severity in adulthood: A 5-year prospective cohort study.
abstract: Objective To test the phenotypic plasticity framework using a polygenic approach in a prospective depression cohort of primary care attendees with and without histories of severe childhood abuse. Methods Depressive symptoms were assessed at baseline and annually for 5 years post-baseline using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9) among 288 adult primary care attendees. Twelve polymorphisms in nine genes were genotyped and polygenic phenotypic plasticity allelic load (PAL) calculated. Linear mixed models assessed differences in depressive symptom severity over the 5-year follow-up period by PAL and history of severe childhood abuse. Results A higher PAL conferred greater depressive symptom severity among those with a history of severe childhood abuse but conferred significantly lower symptom severity among those without this history. Importantly, this interaction withstood adjustments for important covariates (e.g., antidepressant use, comorbid anxiety) and was stable over the 5 years of observation. Conclusions Aligned with the phenotypic plasticity framework, depressive symptom severity was dependent on the interaction between PAL and history of severe childhood abuse in a "for better and for worse" manner. Measures of polygenic phenotypic plasticity, such as ours, may serve as a trait marker of sensitivity to negative and potentially positive environmental influences.
authors.affiliation: a Department of Psychiatry , The University of Melbourne , Parkville , VIC , Australia.|b Department of General Practice , The University of Melbourne , Parkville , VIC , Australia.|c Centre for Human Psychopharmacology , Swinburne University of Technology , Hawthorne , VIC , Australia.|d Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville , VIC , Australia.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Bousman
authors.affiliation: b Department of General Practice , The University of Melbourne , Parkville , VIC , Australia.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Gunn
authors.affiliation: b Department of General Practice , The University of Melbourne , Parkville , VIC , Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Potiriadis
authors.affiliation: a Department of Psychiatry , The University of Melbourne , Parkville , VIC , Australia.|d Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville , VIC , Australia.|e NorthWestern Mental Health , Melbourne , VIC , Australia.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Everall
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D001007:Anxiety / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D019966:Substance-Related Disorders / Q000453:epidemiology; D011795:Surveys and Questionnaires
keywords: Gene–environment interaction; child abuse; depression; differential susceptibility; longitudinal