Article Text

Download PDFPDF

Socioeconomic status and severe mental disorders: a bidirectional multivariable Mendelian randomisation study
  1. Álvaro Andreu-Bernabeu1,
  2. Javier González-Peñas1,
  3. Celso Arango1,2,
  4. Covadonga M Díaz-Caneja1,2
  1. 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  2. 2 Universidad Complutense de Madrid, Madrid, Spain
  1. Correspondence to Dr Álvaro Andreu-Bernabeu, Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM Madrid, ES, Hospital General Universitario Gregorio Marañón, Madrid 28009, Spain; a.andreu.bernabeu{at}


Background Despite the evidence supporting the relationship between socioeconomic status (SES) and severe mental disorders (SMD), the directionality of the associations between income or education and mental disorders is still poorly understood.

Objective To investigate the potential bidirectional causal relationships between genetic liability to the two main components of SES (income and educational attainment (EA)) on three SMD: schizophrenia, bipolar disorder (BD) and depression.

Methods We performed a bidirectional, two-sample univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR) study using SES phenotypes (income, n=397 751 and EA, n=766 345) and SMD (schizophrenia, n=127 906; BD, n=51 710 and depression, n=500 119) genome-wide association studies summary—statistics to dissect the potential direct associations of income and EA with SMD.

Findings UVMR showed that genetic liability to higher income was associated with decreased risk of schizophrenia and depression, with a smaller reverse effect of schizophrenia and depression on income. Effects were comparable after adjusting for EA in the MVMR. UMVR showed bidirectional negative associations between genetic liability to EA and depression and positive associations between genetic liability to EA and BD, with no significant effects on schizophrenia. After accounting for income, MVMR showed a bidirectional positive direction between genetic liability to EA and BD and schizophrenia but not with depression.

Conclusions Our results suggest a heterogeneous link pattern between SES and SMD. We found a negative bidirectional association between genetic liability to income and the risk of schizophrenia and depression. On the contrary, we found a positive bidirectional relationship of genetic liability to EA with schizophrenia and BD, which only becomes apparent after adjusting for income in the case of schizophrenia.

Clinical implications These findings shed light on the directional mechanisms between social determinants and mental disorders and suggest that income and EA should be studied separately in relation to mental illness.

  • Schizophrenia & psychotic disorders
  • Adult psychiatry
  • Depression & mood disorders

Data availability statement

Data are available in a public, open access repository.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available in a public, open access repository.

View Full Text

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Twitter @andreu_bernabeu

  • Contributors AA-B is guarantor and was responsible for the planning, conception, analysis and writing of the article. JG-P contributed to the analysis and provided critical revisions to the manuscript. CA contributed to the interpretation of results and provided critical revisions to the manuscript. CMD-C was involved in the conception, critical manuscript revisions and editing of the article.

  • Funding This work was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI17/00997, PI19/01024, PI20/00721), co-financed by ERDF Funds from the European Commission, 'A way of making Europe', CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN), and FP7- HEALTH-2013-2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz, and Fundación Mutua Madrileña. The authors acknowledge the valuable commentaries provided by Nicolas Crossley. AA-B holded a Rio Hortega Grant during the development of the research from Instituto de Salud Carlos III (CM20/00114). CMD-C holds a Juan Rodés Grant from Instituto de Salud Carlos III (JR19/00024).

  • Competing interests CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. CMD-C. has received honoraria from AbbVie, Sanofi and Exeltis. The rest of the authors declare no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.