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BMC Medicine
Published in: BMC Medicine 1/2024

Open Access 01-12-2024 | Mood Disorders | REGISTERED REPORT

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

Authors: Adrian Dahl Askelund, Robyn E. Wootton, Fartein A. Torvik, Rebecca B. Lawn, Helga Ask, Elizabeth C. Corfield, Maria C. Magnus, Ted Reichborn-Kjennerud, Per M. Magnus, Ole A. Andreassen, Camilla Stoltenberg, George Davey Smith, Neil M. Davies, Alexandra Havdahl, Laurie J. Hannigan

Published in: BMC Medicine | Issue 1/2024

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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.
Appendix
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Metadata
Title
Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study
Authors
Adrian Dahl Askelund
Robyn E. Wootton
Fartein A. Torvik
Rebecca B. Lawn
Helga Ask
Elizabeth C. Corfield
Maria C. Magnus
Ted Reichborn-Kjennerud
Per M. Magnus
Ole A. Andreassen
Camilla Stoltenberg
George Davey Smith
Neil M. Davies
Alexandra Havdahl
Laurie J. Hannigan
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2024
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-024-03361-8

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