Neuroendocrine responses and coupling to laboratory-induced stress in problem gambling and heavy smoking

• Published in: Psychoneuroendocrinology Vol. 177; p. 107469
• Main Authors: Wemm, Stephanie E., Holzhauer, Cathryn G., Harrison, Luke, Milivojevic, Verica, Fogelman, Nia, Cao, Zhimin Tim, Wulfert, Edelgard
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2025
• Subjects: Adult; Behavior, Addictive - metabolism; Behavior, Addictive - physiopathology; Cigarette Smoking - metabolism; Cortisol; Dehydroepiandrosterone (DHEA); Dehydroepiandrosterone - analysis; Dehydroepiandrosterone - metabolism; Dehydroepiandrosterone Sulfate; Female; Gambling - metabolism; Gambling - physiopathology; Gambling - psychology; Humans; Hydrocortisone - analysis; Hydrocortisone - metabolism; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; Male; Middle Aged; Pituitary-Adrenal System - metabolism; Problem gambling; Progesterone; Progesterone - analysis; Progesterone - metabolism; Saliva - chemistry; Smoking; Smoking - metabolism; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Testosterone; Testosterone - analysis; Testosterone - metabolism; Dehydroepiandrosterone (DHEA); Testosterone; Cortisol; Progesterone; Problem gambling; Smoking
• ISSN: 0306-4530; 1873-3360; 1873-3360
• DOI: 10.1016/j.psyneuen.2025.107469

Identifying common biological and psychological features of substance and behavioral addictions promises to shed light on the pathophysiology of addictive disorders. By identifying constructs that might be related to common risk factors or learned patterns, we gain insights into addiction mechanisms. Previous studies have shown altered levels of the stress hormone cortisol in individuals with problem gambling. However, it remains unclear whether these alterations extend to other hormones in the hypothalamic-pituitary-adrenal axis (HPA) and to sex steroids in the hypothalamic-pituitary-gonadal axis (HPG) as well as the coupling of these hormones with cortisol. In this study, we examined the effects of a laboratory stressor on HPG axis response as measured by levels of testosterone, progesterone and the downstream neuroactive metabolites dehydroepiandrosterone [DHEA] and its sulfate [DHEA-S]) as well as the coupling of these HPG hormones with HPA axis response in cortisol. We compared individuals with problem gambling or heavy cigarette smoking to healthy controls. While DHEA increased following a stressor implemented via the Trier Social Stress Test (TSST), no other hormones showed stress-related changes. Healthy control participants exhibited increased coupling of cortisol with DHEA during stress. In contrast, coupling remained unchanged in problem gamblers or heavy smokers. These findings suggest that, in addition to attenuated cortisol, the feedback between cortisol and neuroactive steroids like DHEA are similarly altered in individuals with behavioral and substance addictions. •DHEA is reactive to stress inductions similarly in control subjects and those with behavioral or substance addictions.•Problem gambling and heavy smoking was associated with a decoupling of neuroactive steroids with cortisol during stress.•The degree of hormone coupling predicted subjective stress in individuals engaging in addictive behaviors.