| Title: | Insulin resistance and poorer treatment outcomes in depression: evidence from UK Biobank primary care data. |
| Journal: | The British Journal of Psychiatry |
| Published: | 23 Jun 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40548411/ |
| DOI: | https://doi.org/10.1192/bjp.2025.82 |
| URL: | ~Ehttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/82E7C4A2EDFC6DD576F37D5596A32C4E/S0007125025000820a.pdf/div-class-title-insulin-resistance-and-poorer-treatment-outcomes-in-depression-evidence-from-uk-biobank-primary-care-data-div.pdf~ |
Publication 16462
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Abstract
BACKGROUND: Major depressive disorder (MDD) and insulin resistance-related conditions are major contributors to global disability. Their co-occurrence complicates clinical outcomes, increasing mortality and symptom severity.</p>
AIMS: In this study, we investigated the association of insulin resistance-related conditions and related polygenic scores (PGSs) with MDD clinical profile and treatment outcomes, using primary care records from UK Biobank.</p>
METHOD: We identified MDD cases and insulin resistance-related conditions, as well as measures of depression treatment outcomes (e.g. resistance) from the records. Clinical-demographic variables were derived from self-reports, and insulin resistance-related PGSs were calculated using PRS-CS. Univariable analyses were conducted to compare sociodemographic and clinical variables of MDD cases with (IR+) and without (IR-) lifetime insulin resistance-related conditions. Multiple regressions were performed to identify factors, including insulin resistance-related PGSs, potentially associated with treatment outcomes, adjusting for confounders.</p>
RESULTS: Among 30 919 MDD cases, 51.95% were IR+. These had more antidepressant prescriptions and classes utilisation and longer treatment duration than patients without insulin resistance-related conditions (P < 0.001). IR+ participants showed distinctive depressive profiles, characterised by concentration issues, loneliness and inadequacy feelings, which varied according to the timing of MDD diagnosis relative to insulin resistance-related conditions. After adjusting for confounders, insulin resistance-related conditions (i.e. cardiovascular diseases, hypertension, non-alcoholic fatty liver disease, obesity/overweight, prediabetes and type 2 diabetes mellitus) were associated with antidepressant non-response/resistance and longer treatment duration, particularly when MDD preceded insulin resistance-related conditions. No significant PGS associations were found with antidepressant treatment outcomes.</p>
CONCLUSIONS: Our findings support an integrated treatment approach, prioritising both psychiatric and metabolic health, and public health strategies aimed at early intervention and prevention of insulin resistance in MDD.</p>
10 Authors
- Giuseppe Fanelli
- Janita Bralten
- Barbara Franke
- Nina Roth Mota
- Anna Rita Atti
- Diana De Ronchi
- Alessio Maria Monteleone
- Luigi Grassi
- Alessandro Serretti
- Chiara Fabbri
1 Application
| Application ID | Title |
|---|---|
| 56514 | Stratification of health outcomes in mood disorders |
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