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The emergence of chronic diseases of adulthood and middle age in the young: the COIDS (chronic inflammation, obesity, insulin resistance/type 2 diabetes, and depressive syndromes) noxious quartet of pro-inflammatory stress outcomes

Molecular Psychiatry volume 30, pages 3348–3356 (2025)Cite this article

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Abstract

Major depression, type 2 diabetes, and essential (primary) hypertension are chronic medical and psychiatric disorders that have traditionally affected primarily adults and middle-aged individuals. However, recent decades have witnessed an increasing prevalence of these conditions among children and adolescents. For diseases that typically require prolonged exposure to risk factors to emerge in childhood and adolescence, the amount of exposure to a single risk factor would have to be exceptionally high. We advance the alternative hypothesis of multiple factors acting synergistically. Biological mechanisms underlying the response to ongoing (chronic) stress are logical candidates for being a shared pathway. In the context of persistent and synergistic psychological, social, and economic pressures, unremitting stress can lead to such disease outcomes, exerting a direct influence on the emergence of chronic disorders, and it can also contribute to obesity. Depression follows the same trajectory; therefore, we should examine it as an entity whose consequences are directly reflected in behavioral outcomes, including (over-) eating. Other contributing pathways include chronic sleep deprivation, epigenetic modifications, telomere shortening, the physical environment, pathogens, and the microbiome. We introduce here the concept of the Chronic inflammation, Obesity, Insulin resistance/type 2 diabetes, and Depressive Syndromes (COIDS) noxious quartet of pro-inflammatory stress outcomes, as an increasingly common pathophysiologic state, representing a distinct presentation of type 2 allostatic overload, with direct implications for the current chronic disease epidemic. The compounded effects of a pro-inflammatory state that is fueled by four different and co-existing sources may contribute to explain the emergence of chronic diseases of adulthood and middle age in the young. PPARγ might represent a potential translational therapeutic target for those with COIDS. We propose that highly adverse environments sustain sufficient chronic stress to bring about in the young diseases that had been previously confined to adults.

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Fig. 1: The COIDS (Chronic inflammatory disease syndrome) noxious quartet conceptual framework.

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Notes

  1. BMI – Body Mass Index is the quotient of an individual’s weight in kilograms by the square root of his height in meters. Overweight and obesity are widely regarded as having BMIs above 25 and 30 kg/m2, respectively.

  2. GDP – Gross Domestic Product is a measure of the size of a region’s economy, commonly defined as the market value of all final goods and services produced within a country in a given period of time.

  3. NHANES – The National Health and Nutrition Examination Survey is an ongoing survey conducted by the United States Center for Disease Control and the National Centers for Health Statistics designed to assess the health and nutritional status of adults and children in the United States through interviews and direct physical examinations.

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Funding

Grants R01MH127423, R21MH128726, R21MH126405, National Institute of Mental Health, National Institutes of Health, USA awarded to JL and MLW.

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Authors and Affiliations

  1. State University of New York, Upstate Medical University, 505 Irving Ave 3302, Syracuse, NY, 13210, USA

    Julio Licinio & Ma-Li Wong

  2. Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milano, MI, Italy

    Alice W. Licinio

  3. Montrose Behavioral Health Hospital, 4720 N Clarendon Ave, Chicago, IL, 60640, USA

    João Vicente Busnello

  4. Ascension Saint Joseph – Chicago, 2900 N Lake Shore Dr, Chicago, IL, 60657, USA

    Luciana Ribeiro

  5. Intramural Research Program, National Institute of Mental Health, NIH Clinical Center 2D-46-1284, Bethesda, MD, 20814-1284, USA

    Philip W. Gold

  6. Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Stefan R. Bornstein

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  1. Julio Licinio
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  7. Ma-Li Wong
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Contributions

JL: contributed the manuscript writing, original draft, revision, and created and prepared Fig. 1; AWL: contributed the manuscript writing and original draft, JVB: contributed the manuscript writing and original draft; LR: contributed the manuscript writing and original draft; PWG: contributed the manuscript writing and original draft; SRB: contributed the manuscript writing and original draft, and Ma-Li Wong: contributed the manuscript writing, original draft, and revision.

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Licinio, J., Licinio, A.W., Busnello, J.V. et al. The emergence of chronic diseases of adulthood and middle age in the young: the COIDS (chronic inflammation, obesity, insulin resistance/type 2 diabetes, and depressive syndromes) noxious quartet of pro-inflammatory stress outcomes. Mol Psychiatry 30, 3348–3356 (2025). https://doi.org/10.1038/s41380-025-03034-9

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