CONCEPTUAL ANALYSIS article
Front. Psychiatry
Sec. Adolescent and Young Adult Psychiatry
The role of gene-environment interactions in endocrine-sensitive life stages for shaping mental health: focus on the RE-MEND project
Khalwa Abualia 1,2
Andrea Cediel-Ulloa 3
Philip Allsopp 4
Angelika Augustine 5
Jonas Bergquist 6
Carl-Gustav Bornehag 7,8
Karin Broberg 9
Nicolò Caporale 10,11
Erika Comasco 12
Diego Di Bernardo 13
Rosário Domingues 14,15
Elina Drakvik 16
Chris Gennings 17
Malin Gingnell 18
Daniel Globisch 19
Maria Kippler 20
Emeir McSorley 4
Maria Mulhern 4
Hitesh Motwani 21,22,23
Ivan Nalvarte 24,25
Anna Oudin 26,27
Anisur Rahman 28
Doreen Reifegerste 5
Theo Rein 29
Alkistis Skalkidou 30
JJ Strain 4
Giuseppe Testa 31,11
Liudmyla Tsiukalo 32
Edwin van Wijngaarden 33
Alison Yeates 4
Joëlle Rüegg 34
Philipp Antczak 1,2,35
1. Department II of Internal Medicine, University Hospital of Cologne, Cologne, Germany
2. University of Cologne Center for Molecular Medicine Cologne, Cologne, Germany
3. Department of Organismal Biology, Physiology and Environmental Toxicology, Uppsala Universitet, Uppsala, Sweden
4. Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, United Kingdom
5. School of Public Health, Universitat Bielefeld, Bielefeld, Germany
6. Department of Chemistry– BMC, Analytical Chemistry and Neurochemistry, Uppsala Universitet, Uppsala, Sweden
7. Department of Health Sciences, Karlstads universitet, Karlstad, Sweden
8. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, United States
9. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lunds Universitet, Lund, Sweden
10. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
11. Fondazione Human Technopole, Milan, Italy
12. Department of Women’s and Children’s Health, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden
13. Department Chemical, Materials and Industrial Engineering, Telethon Institute of Genetics and Medicine, Universita degli Studi di Napoli Federico II, Naples, Italy
14. Department of Chemistry, Lipidomics Laboratory, Mass Spectrometry Centre, Universidade de Aveiro, Aveiro, Portugal
15. Universidade de Aveiro Centro de Estudos do Ambiente e do Mar, Aveiro, Portugal
16. Finnish Institute of Occupational Health, Helsinki, Finland
17. Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, United States
18. Experimental Cognitive and Affective Neuroscience Lab, Department of Medical Sciences, Uppsala Universitet, Uppsala, Sweden
19. Department of Chemistry - BMC, Science for Life Laboratory, Uppsala Universitet, Uppsala, Sweden
20. Karolinska Institutet, Stockholm, Sweden
21. Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota Twin Cities, Minneapolis, United States
22. Department of Environmental Science, Stockholms Universitet, Stockholm, Sweden
23. School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
24. Department of Neurobiology Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden
25. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
26. Department of Epidemiology and Global Health, Sustainable Health, Umea Universitet, Umeå, Sweden
27. Department of Laboratory Medicine, Lunds Universitet, Lund, Sweden
28. Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
29. Department of Translational Research in Psychiatry, Project Group Molecular Pathways of Depression, Max-Planck-Institut fur Psychiatrie, Munich, Germany
30. Department of Women’s and Children’s Health, Uppsala Universitet, Uppsala, Sweden
31. Department of Oncology and Hemato-Oncology, Universita degli Studi di Milano, Milan, Italy
32. Department of Chemistry for Life Sciences, Uppsala Universitet, Uppsala, Sweden
33. The Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, United States
34. Department of Organismal Biology, Uppsala Universitet, Uppsala, Sweden
35. Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, Germany
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Abstract
Abstract The number of people seeking help for mental illness is increasing across all ages, creating a major burden for individuals, families, and the society. While personalized medicine is advancing in other fields, diagnosis and treatment of mental disorders remain largely symptom-based and fail to capture individual, sex, and gender differences in risk, manifestation, and treatment response. Early signs of illness often go unnoticed due to the lack of monitoring tools, and stigma continues to hinder prevention and care. In some phases of life, an individual's susceptibility to mental illness is heightened and may be influenced by changes in endocrine signalling. To address these challenges, the research project Building REsilience against MEntal illness during ENDocrine-sensitive life stages (RE-MEND) has implemented an interdisciplinary approach focusing on four critical endocrine-sensitive life stages: prenatal, puberty, peripartum, and older age. The project integrates longitudinal population-based cohorts with experimental and clinical studies to identify genetic, environmental, and endocrine factors shaping susceptibility and resilience to mental illness. Multi-omics data (genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and adductomics) will be combined with neurobiological, clinical, and behavioural measures, analysed using advanced biostatistics and machine learning. RE-MEND seeks to i) identify risk and resilience factors affecting mental health; ii) deliver biomarker panels for susceptibility, disease progression, and treatment response across sensitive life stages; iii) discover novel drug targets through repurposing strategies, and iv) promote mental health literacy and reduce stigma. The integration of biological research with communication science is anticipated to result in translatable findings, supporting earlier intervention and more effective care.
Summary
Keywords
endocrine-sensitive life stage, Mental Health, mental illness, resilience, stigma, susceptibility
Received
03 November 2025
Accepted
27 January 2026
Copyright
© 2026 Abualia, Cediel-Ulloa, Allsopp, Augustine, Bergquist, Bornehag, Broberg, Caporale, Comasco, Di Bernardo, Domingues, Drakvik, Gennings, Gingnell, Globisch, Kippler, McSorley, Mulhern, Motwani, Nalvarte, Oudin, Rahman, Reifegerste, Rein, Skalkidou, Strain, Testa, Tsiukalo, van Wijngaarden, Yeates, Rüegg and Antczak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Joëlle Rüegg; Philipp Antczak
Disclaimer
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