Stratifying early‐onset emotional disorders: using genetics to assess persistence in young people of European and South Asian ancestry

Author:

Dennison Charlotte A.12ORCID,Martin Joanna12ORCID,Shakeshaft Amy12ORCID,Riglin Lucy12ORCID,Rice Frances12ORCID,Lewis Cathryn M.3,O'Donovan Michael C.2,Thapar Anita12

Affiliation:

1. Wolfson Centre for Young People's Mental Health Cardiff University Cardiff UK

2. Centre for Neuropsychiatric Genetics and Genomics, School of Medicine Cardiff University Cardiff UK

3. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK

Abstract

BackgroundDepression and anxiety are the most common mental health problems in young people. Currently, clinicians are advised to wait before initiating treatment for young people with these disorders as many spontaneously remit. However, others develop recurrent disorder but this subgroup cannot be identified at the outset. We examined whether psychiatric polygenic scores (PGS) could help inform stratification efforts to predict those at higher risk of recurrence.MethodsProbable emotional disorder was examined in two UK population cohorts using the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ). Those with emotional disorder at two or more time points between ages 5 and 25 years were classed as ‘recurrent emotional disorder’ (n = 1,643) and those with emotional disorder at one time point as having ‘single episode emotional disorder’ (n = 1,435, controls n = 8,715). We first examined the relationship between psychiatric PGS and emotional disorders in childhood and adolescence. Second, we tested whether psychiatric PGS added to predictor variables of known association with emotional disorder (neurodevelopmental comorbidity, special educational needs, family history of depression and socioeconomic status) when discriminating between single‐episode and recurrent emotional disorder. Analyses were conducted separately in individuals of European and South Asian ancestry.ResultsProbable emotional disorder was associated with higher PGS for major depressive disorder (MDD), anxiety, broad depression, ADHD and autism spectrum disorder (ASD) in those of European ancestry. Higher MDD and broad depression PGS were associated with emotional disorder in people of South Asian ancestry. Recurrent, compared to single‐episode, emotional disorder was associated with ASD and parental psychiatric history. PGS were not associated with episode recurrence, and PGS did not improve discrimination of recurrence when combined with clinical predictors.ConclusionsOur findings do not support the use of PGS as a tool to assess the likelihood of recurrence in young people experiencing their first episode of emotional disorder.

Funder

Health and Care Research Wales

Medical Research Council

Wellcome Trust

Wolfson Foundation

Publisher

Wiley

Subject

Psychiatry and Mental health,Developmental and Educational Psychology,Pediatrics, Perinatology and Child Health

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1. Exome sequencing of UK birth cohorts;Wellcome Open Research;2024-07-19

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