ReviewThe application of clinical genetics2014
Hypothesis of the neuroendocrine cortisol pathway gene role in the comorbidity of depression, type 2 diabetes, and metabolic syndrome.
Review in The application of clinical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Association of metabolic syndrome and its components with the risk of depressive symptoms: A systematic review and meta-analysis of cohort studies.Journal of affective disorders · 2023Pooled it
- A Systematic Review and Meta-Analysis of the Prevalence and Risk Factors of Depression in Type 2 Diabetes Patients in China.Frontiers in medicine · 2022Pooled it
- Combined Associations of Diabetes and Depressive Symptoms on Cognitive Impairment Risk in the Population Aged 60 or Older: Cross-Cohort Comparisons From NHANES and CHARLS.Psychiatry investigation · 2026Article
- Secondary analysis of GenRED data (Genetics of Recurrent Early-Onset major Depression) using MERLIN.European archives of psychiatry and clinical neuroscience · 2026Article
- First-Degree Family History of Diabetes Is Associated With the Presence of Depressive Symptoms Independent of Lifestyle Risk Factors and Cardiometabolic Risk Factors.Journal of diabetes · 2025Article
- The melanocortin receptor genes are linked to and associated with the risk of polycystic ovary syndrome in Italian families.Journal of ovarian research · 2024Article
- A new model for the treatment of type 2 diabetes mellitus based on rhythm regulations under the framework of psychosomatic medicine: a real-world study.Scientific reports · 2023Article
- Targeting the Arginine Vasopressin VNeuropsychiatric disease and treatment · 2023Review
- Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.BMC psychiatry · 2022Article
- Familial Linkage and Association of theInternational journal of molecular sciences · 2022Article
- Comorbidity of NovelInternational journal of molecular sciences · 2022Article
- Implication of Melanocortin Receptor Genes in the Familial Comorbidity of Type 2 Diabetes and Depression.International journal of molecular sciences · 2022Article
- Comorbidity of Mental Disorder in Patients with Chronic Disease: A Comparative Study of Heroin Dependence Patients and Diabetes Mellitus Patients.Iranian journal of public health · 2022Article
- Association of FKBP5 genotype with depressive symptoms in patients with coronary heart disease: a prospective study.Journal of neural transmission (Vienna, Austria : 1996) · 2020Article
- Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression-A Literature Review.International journal of molecular sciences · 2020Review
- Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes.World journal of diabetes · 2020Review
- Atorvastatin ameliorates depressive behaviors and neuroinflammatory in streptozotocin-induced diabetic mice.Psychopharmacology · 2020Article
- The Importance of DS-14 and HADS Questionnaires in Quantifying Psychological Stress in Type 2 Diabetes Mellitus.Medicina (Kaunas, Lithuania) · 2019Article
- Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.Frontiers in neuroendocrinology · 2019Review
- Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.European journal of nutrition · 2019Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression, type 2 diabetes (T2D), and metabolic syndrome (MetS) are often comorbid. Depression per se increases the risk for T2D by 60%. This risk is not accounted for by the use of antidepressant therapy. Stress causes hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, by triggering the hypothalamic corticotropin-releasing hormone (CRH) secretion, which stimulates the anterior pituitary to release the adrenocorticotropin hormone (ACTH), which causes the adrenal secretion of cortisol. Depression is associated with an increased level of cortisol, and CRH and ACTH at inappropriately "normal" levels, that is too high compared to their expected lower levels due to cortisol negative feedback. T2D and MetS are also associated with hypercortisolism. High levels of cortisol can impair mood as well as cause hyperglycemia and insulin resistance and other traits typical of T2D and MetS. We hypothesize that HPA axis hyperactivation may be due to variants in the genes of the CRH receptors (CRHR1, CRHR2), corticotropin receptors (or melanocortin receptors, MC1R-MC5R), glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), and of the FK506 binding protein 51 (FKBP5), and that these variants may be partially responsible for the clinical association of depression, T2D and MetS. In this review, we will focus on the correlation of stress, HPA axis hyperactivation, and the possible genetic role of the CRHR1, CRHR2, MCR1-5, NR3C1, and NR3C2 receptors and FKBP5 in the susceptibility to the comorbidity of depression, T2D, and MetS. New studies are needed to confirm the hypothesized role of these genes in the clinical association of depression, T2D, and MetS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.