A prospective observational cohort study: neurotoxic processes associated with psychiatric symptoms in heroin use disorder: the kynurenine pathway and neopterin levels

Güleser Akpınar; Mehtap Sarıoğlu; Gözde Girgin; Terken Baydar; Hande Sipahi

doi:10.3389/fpsyt.2026.1785477

A prospective observational cohort study: neurotoxic processes associated with psychiatric symptoms in heroin use disorder: the kynurenine pathway and neopterin levels

Front Psychiatry. 2026 Apr 2:17:1785477. doi: 10.3389/fpsyt.2026.1785477. eCollection 2026.

Authors

Güleser Akpınar^{1

2}, Mehtap Sarıoğlu³, Gözde Girgin⁴, Terken Baydar⁴, Hande Sipahi^{5

6}

Affiliations

¹ Department of Emergency Medicine, Yeditepe University, Institute of Health Sciences, Çam ve Sakura City Hospital Programme of Pharmaceutical Toxicology, Istanbul, Türkiye.
² Çamsakura City Hospital, Istanbul, Türkiye.
³ Department of Psychiatry Bakırköy Mazhar Osman Training and Research Hospital for Mental Health and Neurological Disorders, Istanbul, Türkiye.
⁴ Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Sihhiye, Ankara, Türkiye.
⁵ Department of Toxicology, Faculty of Pharmacy, Yeditepe University, Istanbul, Türkiye.
⁶ Department of Toxicology, Faculty of Pharmacy, University of Health Sciences, Istanbul, Türkiye.

Abstract

Aim: This study investigated the effects of tryptophan (TRP) metabolism, kynurenine pathway (KP) and neopterin levels in heroin use disorder (HUD) in relation to neurotoxicity, treatment processes and psychiatric recovery.

Method: The study groups consisted of patients with HUD who sought treatment at the hospital and received treatment, and a healthy control (C) group. The levels of neopterin, tryptophan and kynurenine in the participants' serum were determined, and the pre- and post-treatment results in the groups were compared with the controls.

Results: Neopterin levels, reflecting immune system activation, were observed to decrease in HUD group after treatment (p = 0.021). Similarly, a decrease in levels of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, was also detected after treatment (p < 0.05). However, changes in interleukin-6 (IL-6) and interferon-gamma (IFN-γ) levels were not found to be significant (p > 0.05). The total scores of the Addiction Profile Index (API-K), which measures the severity of addiction, decreased significantly after treatment (p < 0.001). At the same time, improvement was observed in the general symptom level (GSI) and all subscales (including depression, anxiety, obsessive-compulsive disorders, and somatization) of the Symptom Checklist-90-Revised (SCL-90-R) scale, which assesses general psychopathology. Regression analyses revealed that the two strongest factors negatively affecting treatment success in the HUD group were duration of use (p = 0.028) and high neopterin levels (p = 0.020).

Conclusion: This study highlights the critical role of immunological and neuroinflammatory processes in the success of HUD treatment. The findings indicate that biochemical recovery progresses in parallel with psychiatric recovery during treatment, and that changes in the KYN/TRP ratio and IL-6 levels have strong diagnostic and prognostic value. Neopterin, kynurenine, and tryptophan, on the other hand, have moderate prognostic value.

Keywords: heroin use disorder; kynurenine pathway; neopterin; neuroinflammation; psychiatric symptoms; tryptophan metabolism.