ArticleMolecular psychiatry2025
Evidence of bidirectional relationship between type 2 diabetes and depression; a Mendelian randomization study.
Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Chronic social defeat stress induces a hypoglycemic shift and depression-related behaviors, both prevented by antidiabetic drugs.The international journal of neuropsychopharmacology · 2026Article
- The Gut Microbiota-Astrocyte Axis: New Insights into the Mechanisms of Comorbid Major Depressive Disorder in Type 2 Diabetes Mellitus.Molecular neurobiology · 2026Review
- Sotagliflozin pretreatment attenuates acute LPS-induced depression-like behavioral abnormalities and modulates the gut microbiota-immune-brain axis.Psychopharmacology · 2026Article
- Evaluation of Depression in Adults With and Without Type 2 Diabetes Mellitus: A Comparative Study.Cureus · 2026Article
- Trends in obesity prevalence among adults with depression in the United States, 2005 to 2023.BMC psychiatry · 2026Article
- Combining polygenic risk scores to understand genetic liability to physical-mental health multimorbidity in UK Biobank.Human molecular genetics · 2026Article
- Does Administration of Low-Dose Aspirin Enhance the Efficacy of Psychotropic Drugs in Patients with Bipolar Disorder, Schizophrenia, and Schizoaffective Disorder?Pharmaceuticals (Basel, Switzerland) · 2026Article
- Psychological Distress and Health-Related Quality of Life in Romanian Adults with Diabetes Mellitus: A Cross-Sectional Study.Healthcare (Basel, Switzerland) · 2026Article
- Metabolic dysfunction and insulin resistance in depression: mechanisms, evidence, and therapeutic implications.Frontiers in psychiatry · 2026Review
- Single Nucleotide Polymorphisms in Orexin-1 and BDNF Receptor Genes are Associated with Increased Risk of Developing Postpartum Depression among Women with Gestational Diabetes Mellitus.Public health genomics · 2026Article
- Depression and Its Association With Microvascular and Macrovascular Complications in Type 2 Diabetes.Journal of diabetes research · 2026Article
- Estimated glucose disposal rate and the dynamic transitions of cardiometabolic multimorbidity and all-cause mortality in prediabetes: a multistate trajectory analysis.Lipids in health and disease · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Major depressive disorder (MDD) and type 2 diabetes (T2D) represent two global health challenges with a high degree of co-occurrence. Here, we aim to investigate the causal relationship between MDD and T2D in diverse ancestries using Mendelian randomization (MR) in GWAS summary statistic and individual level (UK Biobank (UKB)) data. We assessed the bi-directional causal relationship between: (a) MDD and T2D and (b) MDD and glycaemic biomarkers (e.g. TG:HDL-C ratio, a measure of insulin resistance, fasting glucose) in non-diabetic individuals. In UKB we also tested the role of T2D on treatment resistant depression (TRD). We used multivariable MR (MVMR) to assess the role of body mass index (BMI) in the MDD to T2D relationship. Our results demonstrated that a doubling in MDD genetic liability was associated with 1.14 higher odds of T2D (95% CI:1.09, 1.19), whilst a doubling in T2D genetic liability associated with 1.02 higher odds of MDD (95% CI:1.01, 1.03). Consistent effect estimates were observed in the UKB when stratifying by sex and suggested a role for T2D in TRD. T2D GWAS derived clusters of genetic variants highlighted the importance of specific pathways in the MDD relationship, including variants raising T2D risk via body fat (OR:1.04; 95% CI:1.02, 1.06), obesity mediated insulin resistance (OR:1.06; 95% CI:1.04, 1.09) and residual glycaemic (OR: 1.02; 95% CI:1.00, 1.04) pathways. MVMR with BMI attenuated the bidirectional relationship between MDD and T2D, particularly from MDD to T2D. Genetic liability to MDD was also associated with higher TG:HDL-C ratio in individuals without T2D (β:0.11; 95% CI:0.08, 0.14). We provide evidence of bidirectional causal association between MDD and T2D, with MDD strongly predicting insulin resistance and T2D. T2D predicted both MDD and TRD and highlighted the importance of obesity and body fat pathways in the T2D to MDD relationship.
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