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. 2025 May 2. doi: 10.1038/s41380-025-03034-9. Online ahead of print.

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.

PMID:40316674 | DOI:10.1038/s41380-025-03034-9