Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study
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 inv...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-024-03361-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adrian Dahl Askelund |
| collection | DOAJ |
| description | 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], p one-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (β = − 0.07, 95% CI [− 0.13, 0.00], p one-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], p one-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. |
| first_indexed | 2024-04-24T09:51:56Z |
| format | Article |
| id | doaj.art-29d3f4adc7b245f58693f6795fcdf5dd |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-24T09:51:56Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-29d3f4adc7b245f58693f6795fcdf5dd2024-04-14T11:18:40ZengBMCBMC Medicine1741-70152024-04-0122112710.1186/s12916-024-03361-8Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation studyAdrian Dahl Askelund0Robyn E. Wootton1Fartein A. Torvik2Rebecca B. Lawn3Helga Ask4Elizabeth C. Corfield5Maria C. Magnus6Ted Reichborn-Kjennerud7Per M. Magnus8Ole A. Andreassen9Camilla Stoltenberg10George Davey Smith11Neil M. Davies12Alexandra Havdahl13Laurie J. Hannigan14Department of Psychology, University of OsloNic Waals Institute, Lovisenberg Diaconal HospitalDepartment of Psychology, University of OsloDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthPsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public HealthNic Waals Institute, Lovisenberg Diaconal HospitalCentre for Fertility and Health, Norwegian Institute of Public HealthPsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public HealthCentre for Fertility and Health, Norwegian Institute of Public HealthNORMENT Centre, Institute of Clinical Medicine, University of OsloDepartment of Global Public Health and Primary Care, University of BergenMRC Integrative Epidemiology Unit, Bristol Medical School, University of BristolDivision of Psychiatry, University College LondonNic Waals Institute, Lovisenberg Diaconal HospitalNic Waals Institute, Lovisenberg Diaconal HospitalAbstract 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], p one-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (β = − 0.07, 95% CI [− 0.13, 0.00], p one-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], p one-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.https://doi.org/10.1186/s12916-024-03361-8DepressionAge at menarcheMendelian randomisationMoBaMBRN |
| spellingShingle | 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 Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study BMC Medicine Depression Age at menarche Mendelian randomisation MoBa MBRN |
| title | Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study |
| title_full | Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study |
| title_fullStr | Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study |
| title_full_unstemmed | Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study |
| title_short | Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study |
| title_sort | assessing causal links between age at menarche and adolescent mental health a mendelian randomisation study |
| topic | Depression Age at menarche Mendelian randomisation MoBa MBRN |
| url | https://doi.org/10.1186/s12916-024-03361-8 |
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