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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 Ketamine Addiction Axons Neurofilaments Major depressive disorder

Chun-Hao Chen,1 Ming-Chyi Huang,2 Yi-Hang Chiu,3 I-Ming Chen,1,4 Chun-Hsin Chen,3,5 Mong-Liang Lu,3,5 Tsung-Yang Wang,1 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 3Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan; 4Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 5Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen, Department of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, Taiwan, Tel +886-2-2312-3456 ext. 66787, Fax +886-2-2381-3208, Email hsichungchen@ntu.edu.twObjective: This study aimed to investigate the relationship between eveningness preference and poor sleep quality and eventually examine the moderation effect of stress susceptibility.Methods: Individuals with non-acute major depressive disorder or bipolar affective disorder and healthy participants were recruited. The Composite Scale of Morningness (CSM) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate chronotype and sleep quality, respectively. Eysenck Personality Questionnaire, Tridimensional Personality Questionnaire, Perceived Stress Scale, and Beck Anxiety Inventory were used to formulate stress susceptibility and as indicator variables for empirical clustering by latent class analysis (LCA). Linear regression models were used to examine the relationship between chronotype preference and sleep quality. The interaction terms of CSM and stress susceptibility were examined for the moderation effect.Results: A total of 887 individuals were enrolled i

Sze-Yu Chen,1 Chun-Hao Chen,1 Chen Lo,1 Mong-Liang Lu,2 Cheng-Dien Hsu,3 Yi-Hang Chiu,2 Chun-Hsin Chen,2 Shih-Ku Lin,4,5 Ming-Chyi Huang,5 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Psychosomatic Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen Email hsichungchen@ntu.edu.twPurpose: This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders.Patients and Methods: Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences.Results: In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class

Yu-Chun Hung,1 Hsi-Chung Chen,2 Po-Hsiu Kuo,2,3 Mong-Liang Lu,4,5 Ming-Chyi Huang,6 Chun-Hsin Chen,4,5 Sabrina Wang,7 Wei-Chung Mao,8 Chang-Shiann Wu,9 Tzu-Hua Wu1,5,10,11 1Division of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 110, Taiwan; 2Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 4Department of Psychiatry, Wan Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Psychiatric Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 6Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 7Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 8Department of Psychiatry, Cheng-Hsin General Hospital, Taipei, Taiwan; 9Department of Information Management, College of Management, National Formosa University, Huwei Township, Yunlin County, Taiwan; 10Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 11Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan;Correspondence: Tzu-Hua WuDivision of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, TaiwanTel +886-227361661 ext. 6172Email thwu@tmu.edu.twIntroduction: Efforts have been made in assessing efficacy and tolerability to various antidepressants, but understanding personalized chances of stability to medication switching sequence is still inconclusive. This study aimed to identify naturalistic switching patterns of medication in stratifying MDD patients.Methods: MDD patients were stratified based on treatment diff