Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity

Stuart, Michael J.; Baune, Bernhard T.

doi:10.1016/j.neubiorev.2011.10.001

Cited by 257Tryptophan and brain disordersAdipokines, Inflammation, and Metabolic DiseasesStress Responses and Cortisol

Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity

Stuart, Michael J., Baune, Bernhard T.·2012·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2011.10.001

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Abstract

Unipolar depression and diabetes mellitus each account for a significant proportion of the global burden of disease. Epidemiological literature suggests a bi-directional relationship between these two common disorders, and evidence from the molecular sciences supports a role for inflammation in the pathogenesis and pathophysiology of each disorder individually. Recent advances in understanding the neurobiology of depression have implicated dysfunction of the hypothalamus-pituitary-adrenal axis, neurotrophins, and inflammatory mediators in the development of this disorder. Similarly, dysregulated facets of both the innate and adaptive immune system have been implicated in the onset of insulin resistance and type 2 diabetes. This review draws upon an emerging body of epidemiological and mechanistic evidence to support the hypothesis that shared inflammatory mechanisms may represent a key biological link in this co-morbidity. Given the shared mechanisms of this co-morbidity, these patients may be excellent candidates for novel immune targeted pharmacotherapy.

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Comorbid metabolic disturbances aggravate the burden of depressive illness, in part by sharing common risk factors and pathophysiological pathways, since impaired insulin signaling and insulin resistance play an important role in the pathogenesis of major depressive disorder.
“Comorbid metabolic disturbances aggravate the burden of depressive illness, in part by sharing common risk factors and pathophysiological pathways, since impaired insulin signaling and insulin resistance have been documented to play an important role in the pathogenesis of MDD [109].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [109]

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The relationship between depression and diabetes mellitus: findings from the Hertfordshire Cohort Study
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Associations Between Depressive Symptoms and Inflammatory/Hemostatic Markers in Women During the Menopausal Transition
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Adipocytokines and Incident Diabetes Mellitus in Older Adults
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Type 2 diabetes does not increase risk of depression
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β-cell apoptosis in type 2 diabetes: quantitative and functional consequences
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IL-1β-Mediated Innate Immunity Is Amplified in the db/db Mouse Model of Type 2 Diabetes
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In VitroHyperresponsiveness to Tumor Necrosis Factor-α Contributes to Adipokine Dysregulation in Omental Adipocytes of Obese Subjects
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Elevated Macrophage Migration Inhibitory Factor (MIF) is associated with depressive symptoms, blunted cortisol reactivity to acute stress, and lowered morning cortisol
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Is depression related to subsequent diabetes mellitus?
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Prolonged interleukin-6 administration enhances glucose tolerance and increases skeletal muscle PPARα and UCP2 expression in rats
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Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat
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p53 induction contributes to excitotoxic neuronal death in rat striatum through apoptotic and autophagic mechanisms
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So depression is an inflammatory disease, but where does the inflammation come from?
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., et al. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-200 · Cited by 1,423 · see citing works
Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder
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Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression
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Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
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Insulin resistance in brain alters dopamine turnover and causes behavioral disorders
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Depression and risk of mortality in individuals with diabetes: a meta-analysis and systematic review
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Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA)
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Self-citation
Cognitive remission: a novel objective for the treatment of major depression?
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Medicinal mushrooms in prevention and control of diabetes mellitus
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RETRACTED: Chronic Inflammation: Accelerator of Biological Aging
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Retracted
The Ketogenic Diet: 1997
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A meta-analysis of chemokines in major depression
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Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma
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Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders
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The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models
Baune, B. T., Stuart, M. J., Gilmour, A., Wersching, H., Heindel, W. L., Arolt, V., & Berger, K. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.18 · Cited by 159 · see citing works
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Depression in people with type 2 diabetes: current perspectives
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Metformin and ageing: improving ageing outcomes beyond glycaemic control
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Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective
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P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes
Wang, D., Wang, H., Gao, H., Zhang, H., Zhang, H., Wang, Q., & Sun, Z. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00388-1 · Cited by 145 · see citing works
Differential effects of metformin on age related comorbidities in older men with type 2 diabetes
Wang, C.-P., Lorenzo, C., Habib, S. L., Jo, B., & Espinoza, S. E. (2017) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2017.01.013 · Cited by 134 · see citing works
Adverse Effects of Depression on Glycemic Control and Health Outcomes in People with Diabetes
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Depression Among Older Adults with Diabetes Mellitus
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Self Reported Childhood Difficulties, Adult Multimorbidity and Allostatic Load. A Cross-Sectional Analysis of the Norwegian HUNT Study
Tómasdóttir, M. Ó., Sigurdsson, J. A., Pétursson, H., Kirkengen, A. L., Krokstad, S., McEwen, B. S., Hetlevik, I., & Getz, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130591 · Cited by 132 · see citing works
Ambient concentrations of particulate matter and hospitalization for depression in 26 Chinese cities: A case-crossover study
Wang, F., Liu, H., Li, H., Liu, J., Guo, X., Yuan, J., Hu, Y., Wang, J., & Lü, L. (2018) · Environment International · doi:10.1016/j.envint.2018.02.012 · Cited by 108 · see citing works
Impact of Brain Insulin Signaling on Dopamine Function, Food Intake, Reward, and Emotional Behavior
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Sarcopenia and the Common Mental Disorders: a Potential Regulatory Role of Skeletal Muscle on Brain Function?
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Depression can be prevented by astaxanthin through inhibition of hippocampal inflammation in diabetic mice
Zhou, X., Zhang, F., Hu, X., Chen, J., Tang, R., Zheng, K., & Song, Y. (2016) · Brain Research · doi:10.1016/j.brainres.2016.12.018 · Cited by 96 · see citing works
Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study
Yu, E., Papandreou, C., Ruiz‐Canela, M., Guasch‐Ferré, M., Clish, C. B., Dennis, C., Liang, L., Corella, D., Fitó, M., Razquín, C., et al. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2018.288720 · Cited by 97 · see citing works
Psychiatric disorders as risk factors for type 2 diabetes: An umbrella review of systematic reviews with and without meta-analyses
Lindekilde, N., Rutters, F., Henriksen, J. E., Lasgaard, M., Schram, M. T., Rubin, K. H., Mika Kivimaki, B., Nefs, G., & Pouwer, F. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.108855 · Cited by 98 · see citing works
Association of Youth Depression With Subsequent Somatic Diseases and Premature Death
Leone, M., Kuja‐Halkola, R., Levál, A., D'Onofrio, B. M., Larsson, H., Lichtenstein, P., & Bergen, S. E. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3786 · Cited by 91 · see citing works
Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide
Dang, R., Zhou, X., Tang, M., Xu, P., Gong, X., Liu, Y., Jiao, H., & Jiang, P. (2018) · European Journal of Nutrition · doi:10.1007/s00394-016-1373-z · Cited by 93 · see citing works
Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment
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Diabetes, antidiabetic medications and risk of depression – A population-based cohort and nested case-control study
Wium‐Andersen, I. K., Osler, M., Jørgensen, M. B., Rungby, J., & Wium‐Andersen, M. K. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105715 · Cited by 87 · see citing works
Association of Depressive and Anxiety Disorders With Diagnosed Versus Undiagnosed Diabetes
Meurs, M., Roest, A. M., Wolffenbuttel, B. H. R., Stolk, R. P., de Jonge, P., & Rosmalen, J. G. M. (2015) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000255 · Cited by 87 · see citing works
Is depression the missing link between inflammatory mediators and cancer?
Polityńska, B., Pokorska, O., Wojtukiewicz, A. M., Sawicka, M., Mysliwiec, M., Honn, K. V., Tucker, S. C., & Wojtukiewicz, M. Z. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108293 · Cited by 80 · see citing works
Psychosoziales und Diabetes (Teil 1)
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Diabesity and mood disorders: Multiple links through the microbiota-gut-brain axis
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Longitudinal relationship of diabetes‐related distress and depressive symptoms: analysing incidence and persistence
Ehrmann, D., Kulzer, B., Haak, T., & Hermanns, N. (2015) · Diabetic Medicine · doi:10.1111/dme.12861 · Cited by 77 · see citing works
Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression
Eyre, H. A., Lavretsky, H., Kartika, J., Qassim, A., & Baune, B. T. (2016) · Pharmacopsychiatry · doi:10.1055/s-0042-103159 · Cited by 75 · see citing works
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Association between pro- and anti-inflammatory cytokines and depressive symptoms in patients with diabetes—potential differences by diabetes type and depression scores
Herder, C., SCHMITT, A. J., Budden, F., Reimer, A., Kulzer, B., Roden, M., Haak, T., & Hermanns, N. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0009-2 · Cited by 71 · see citing works
Metformin and ascorbic acid combination therapy ameliorates type 2 diabetes mellitus and comorbid depression in rats
Shivavedi, N., Kumar, M., Tej, G. N. V. C., & Nayak, P. K. (2017) · Brain Research · doi:10.1016/j.brainres.2017.08.019 · Cited by 72 · see citing works
Moderators of the relationship between depression and cardiovascular disorders: a systematic review
Baune, B. T., Stuart, M. J., Gilmour, A., Wersching, H., Arolt, V., & Berger, K. (2012) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2012.05.013 · Cited by 70 · see citing works
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Bifidobacterium: a probiotic for the prevention and treatment of depression
Li, J., Wang, J., Wang, M., Zheng, L., Cen, Q., Wang, F., Li, Z., Pang, R., & Zhang, A. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1174800 · Cited by 75 · see citing works
Depression is linked to hyperglycaemia via suboptimal diabetes self-management: A cross-sectional mediation analysis
SCHMITT, A. J., Reimer, A., Hermanns, N., Kulzer, B., Ehrmann, D., Krichbaum, M., Huber, J., & Haak, T. (2016) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2016.12.015 · Cited by 69 · see citing works
The association between depression, quality of life, and the health care expenditure of patients with diabetes mellitus in Uganda
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Telmisartan attenuates diabetes induced depression in rats
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High-glucose/high-cholesterol diet in zebrafish evokes diabetic and affective pathogenesis: The role of peripheral and central inflammation, microglia and apoptosis
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Authors: Stuart, M. J., & Baune, B. T.
Affiliations: James Cook University (AU)
The University of Adelaide (AU)
Corresponding author: Baune, Bernhard T.
ORCID: Stuart, Michael J.
Baune, Bernhard T.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2012-01
Volume: 36
Issue: 1
Pages: 658-676
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2011.10.001
OpenAlex: W2067054442
Cited by: 257
References: 242
Citations by year: 2026: 10 · 2025: 17 · 2024: 11 · 2023: 12 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 19 · 2018: 23 · 2017: 14 · 2016: 23 · 2015: 26 · 2014: 22 · 2013: 21 · 2012: 7
FWCI: 0.85
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
ResearchOnline - JCU (James Cook University) (submittedVersion)
Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: depression, type 2 diabetes, inflammatory mechanisms, hypothalamic-pituitary-adrenal axis, neurotrophins, insulin resistance, bidirectional comorbidity
MeSH terms: Depression, Diabetes Mellitus, Type 2, Humans, Immune System, Inflammation, Comorbidity

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Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity

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