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

Dennison, Charlotte, Martin, Joanna ORCID:, Shakeshaft, Amy ORCID:, Riglin, Lucy, Rice, Frances ORCID:, Lewis, Cathryn, O'Donovan, Michael ORCID: and Thapar, Anita ORCID: 2023. Stratifying early-onset emotional disorders: using genetics to assess persistence in young people of European and South Asian ancestry. Journal of Child Psychology and Psychiatry 10.1111/jcpp.13862

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Background Depression 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. Methods Probable 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. Results Probable 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. Conclusions Our 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.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Wiley
ISSN: 0021-9630
Date of First Compliant Deposit: 6 June 2023
Date of Acceptance: 26 May 2023
Last Modified: 18 Sep 2023 22:40

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