# The role of gene-environment interactions in endocrine-sensitive life stages for shaping mental health: focus on the RE-MEND project

**Authors:** Khawla Abualia, Andrea Cediel-Ulloa, Philip Allsopp, Angelika Augustine, Jonas Bergquist, Carl-Gustaf Bornehag, Karin Broberg, Nicolò Caporale, Erika Comasco, Diego di Bernardo, Rosário Domingues, Elina Drakvik, Chris Gennings, Malin Gingnell, Daniel Globisch, Maria Kippler, Emeir McSorley, Maria Mulhern, Hitesh V. Motwani, Ivan Nalvarte, Anna Oudin, Anisur Rahman, Doreen Reifegerste, Theo Rein, Alkistis Skalkidou, J. J. Strain, Giuseppe Testa, Liudmyla Tsiukalo, Edwin van Wijngaarden, Alison Yeates, Joëlle Rüegg, Philipp Antczak

PMC · DOI: 10.3389/fpsyt.2026.1738584 · Frontiers in Psychiatry · 2026-02-20

## TL;DR

This paper discusses how gene-environment interactions during key life stages affect mental health and introduces the RE-MEND project to study these factors for better diagnosis and treatment.

## Contribution

The paper introduces RE-MEND, an interdisciplinary project focusing on endocrine-sensitive life stages to uncover mental health risk and resilience factors.

## Key findings

- RE-MEND integrates multi-omics and clinical data to identify mental health risk factors.
- The project aims to develop biomarkers for disease progression and treatment response.
- It seeks to discover new drug targets through repurposing strategies.

## 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.

## Linked entities

- **Diseases:** mental illness (MONDO:0002025)

## Full-text entities

- **Genes:** POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, SLC6A4 (solute carrier family 6 member 4) [NCBI Gene 6532] {aka 5-HTT, 5-HTTLPR, 5HTT, HTT, OCD1, SERT}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, DRD4 (dopamine receptor D4) [NCBI Gene 1815] {aka D4DR}, COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}
- **Diseases:** endocrine-disrupting (MESH:D004700), psychotic (MESH:D011618), ADHD (MESH:D001289), placental dysfunction (MESH:D010922), mental health disorders (OMIM:603663), language delay (MESH:D007805), deaths (MESH:D003643), PND (MESH:D066087), impaired brain development (MESH:D002658), panic (MESH:D016584), cognitive difficulties (MESH:D003072), depression (MESH:D003866), bipolar disorder (MESH:D001714), allergy (MESH:D004342), aggression (MESH:D010554), low (MESH:D009800), MEntal illness (MESH:D001523), anxiety (MESH:D001007), schizophrenia (MESH:D012559), Asthma (MESH:D001249), inflammation (MESH:D007249), trauma (MESH:D014947), MEND (OMIM:300960), Neurotoxic metals (MESH:D013651), inattention (MESH:D001308), prostate cancer (MESH:D011471), sleep problems (MESH:D012893), Major Depression Disorder (MESH:D003865), hyperactivity (MESH:D006948), posttraumatic stress disorders (MESH:D013313), psychiatry disorders (MESH:D009358), anxiety disorder (MESH:D001008), behavioural difficulties (MESH:D051346), suicidal ideation (MESH:D001072), mental health problems (MESH:D000076082), obesity (MESH:D009765)
- **Chemicals:** bisphenols (MESH:C543008), PFAS (-), phthalates (MESH:C032279), lead (MESH:D007854), dopamine (MESH:D004298), serotonin (MESH:D012701), ROS (MESH:D017382), steroid (MESH:D013256), lipid (MESH:D008055), oestradiol (MESH:D004958), cortisol (MESH:D006854), metals (MESH:D008670), norepinephrine (MESH:D009638), GABA (MESH:D005680), progesterone (MESH:D011374), 8-oxo-7,8-dihydro-2'-deoxyguanosine (MESH:D000080242), per- and polyfluoroalkyl substances (MESH:D005466), Testosterone (MESH:D013739)
- **Species:** Enterovirus D (no rank) [taxon 138951], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** Val66Met

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12964206/full.md

## References

119 references — full list in the complete paper: https://tomesphere.com/paper/PMC12964206/full.md

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Source: https://tomesphere.com/paper/PMC12964206