Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology

Ming-Chyi Huang; Chun-Hsin Chen; Tung-Hsia Liu; An-Nie Chung; Yu-Li Liu; Boris B Quednow; Francesco Bavato

doi:10.1016/j.jpsychires.2023.01.009

Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology

J Psychiatr Res. 2023 Feb:158:360-364. doi: 10.1016/j.jpsychires.2023.01.009. Epub 2023 Jan 10.

Authors

Ming-Chyi Huang¹, Chun-Hsin Chen², Tung-Hsia Liu³, An-Nie Chung⁴, Yu-Li Liu⁵, Boris B Quednow⁶, Francesco Bavato⁷

Affiliations

¹ Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
² Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³ Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
⁴ Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
⁵ Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. Electronic address: ylliou@nhri.edu.tw.
⁶ Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy, and Psychosomatics, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
⁷ Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy, and Psychosomatics, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland.

PMID: 36640660
DOI: 10.1016/j.jpsychires.2023.01.009

Abstract

We recently demonstrated that patients with ketamine dependence (KD) have increased serum levels of neurofilament light chain (NfL), a novel marker of active neuroaxonal pathology, with NfL levels being significantly higher in those KD patients comorbid with major depressive disorder (MDD). However, considering that NfL elevation has been associated with both ketamine-related brain pathology and MDD, we could not determine whether the observed elevation of NfL levels was driven by an interaction of KD with MDD or by MDD itself. Therefore, we compared serum NfL levels between 35 patients with MDD without ketamine use (MDD group), 23 with KD without MDD (KD without MDD group), 30 KD with MDD (KD with MDD group), and 86 healthy controls (HC group). Using a 2*2 (KD*MDD) generalized linear model controlling for age, sex, body mass index, and smoking status, we found that KD and KD*MDD interactions, but not MDD factor, significantly affected NfL levels. Posthoc tests showed that the KD with MDD group had significantly higher NfL levels than all other groups. The KD without MDD group also showed higher NfL levels than the MDD and, as shown before, HC groups. The levels in MDD group were not different from the HC group. These results suggest that the interaction of KD with MDD, but not MDD alone, results in increased vulnerability to neuroaxonal pathology.

Keywords: Addiction; Axons; Ketamine; Major depressive disorder; Neurofilaments.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Comorbidity
Depressive Disorder, Major* / epidemiology
Depressive Disorder, Major* / pathology
Humans
Ketamine*

Substances

Ketamine
Biomarkers