ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Anxiety and Stress Disorders
This article is part of the Research TopicMolecular Mechanisms in Psychiatry: Anxiety and Stress, Volume IIView all articles
Elevated Cortisol/DHEA Ratio Mediates the Association Between Symptom Severity and Working Memory Impairment in Drug-Naive, First-Episode OCD
Provisionally accepted
- 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- 2General Hospital of Ningxia Medical University, Yinchuan, China
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Abstract Objective: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in obsessive-compulsive disorder (OCD). However, the cortisol/dehydroepiandrosterone (DHEA) ratio remains poorly characterized in early-stage illness. This study investigated this neuroendocrine marker’s association with executive function in drug-naive, first-episode OCD patients.Methods: Seventy-five drug-naive, first-episode OCD patients and 50 matched healthy controls (HCs) were recruited. Plasma cortisol and DHEA were quantified. Executive functions were assessed using the Stop-Signal Task (response inhibition), 2-back task (working memory), and Wisconsin Card Sorting Test (cognitive flexibility). Data were analyzed using stepwise multiple regression with False Discovery Rate (FDR) correction and mediation modeling.Results: Compared to HCs, the OCD group exhibited deficits in inhibition and working memory, elevated cortisol (P=0.006), reduced DHEA (P<0.001), and a higher cortisol/DHEA ratio (P<0.001). The elevated ratio correlated with symptom severity and poorer inhibitory control (Padj<0.05). Regression identified the ratio as an independent predictor of inhibition deficits (Padj=0.002), while DHEA levels predicted psychomotor slowing in working memory (Padj<0.001). Mediation analysis revealed the ratio mediated the relationship between symptom severity and working memory accuracy (95% CI: -0.0692 to -0.0096), suggesting a "suppression" effect. No hormonal associations were observed for cognitive flexibility.Conclusion: An elevated cortisol/DHEA ratio is a hallmark of drug-naive OCD that independently predicts inhibitory dysfunction. Furthermore, this ratio mediates the impact of symptomatology on working memory. These findings highlight the ratio’s utility as a state-dependent biomarker and suggest that restoring neuroendocrine balance could ameliorate cognitive deficits in OCD.Keywords: Obsessive-compulsive disorder; Cortisol/DHEA ratio; Executive function; Response inhibition; Working memory; Mediation analysis.
Keywords: cortisol/DHEA ratio, Executive Function, Mediation analysis, Obsessive-Compulsive Disorder, response inhibition, working memory
Received: 19 Dec 2025; Accepted: 22 Jan 2026.
Copyright: © 2026 Song, Fang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jianqun Fang
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