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Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study

Askelund, AD; Wootton, RE; Torvik, FA; Lawn, RB; Ask, H; Corfield, EC; Magnus, MC; ... Hannigan, LJ; + view all (2024) Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study. BMC Medicine , 22 (1) , Article 155. 10.1186/s12916-024-03361-8. Green open access

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Abstract

BACKGROUND: The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted. METHODS: In this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health. RESULTS: Our results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (β =  − 0.11, 95% CI [− 0.12, − 0.09], pone-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (β =  − 0.07, 95% CI [− 0.13, 0.00], pone-tailed = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], pone-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding. CONCLUSIONS: We found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

Type: Article
Title: Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12916-024-03361-8
Publisher version: http://dx.doi.org/10.1186/s12916-024-03361-8
Language: English
Additional information: © 2024 BioMed Central Ltd. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Depression, Age at menarche, Mendelian randomisation, MoBa, MBRN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Epidemiology and Applied Clinical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10191544
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