¹Mackay Memorial Hospital, Department of Psychiatry, Taipei, Taiwan, ²Taipei City Psychiatric Center, Taipei City Hospital, Department of Addiction Sciences, Taipei, Taiwan, ³Taipei City Psychiatric Center, Taipei City Hospital, Department of Psychiatry, Taipei, Taiwan

Background: Nectin-4 is a cell adhesion molecule essential for maintaining cell-cell integrity. Previous studies have demonstrated elevated plasma levels of the extracellular domain of Nectin-4 in patients with heroin and ketamine dependence, which correlated with the severity of dependence. However, the role of Nectin-4 in alcohol use disorder (AUD) and its alterations during abstinence following naltrexone treatment remain unclear.

Aims & Objectives: This study aimed to investigate the association between plasma Nectin-4 levels and clinical characteristics in AUD patients and to examine the changes of Nectin-4 during a 12-week treatment period of naltrexone.

Method: A total of 201 patients with AUD were recruited. Sociodemographic data, drinking history, and psychometric assessment including the Beck Anxiety Inventory (BAI) and Penn Alcohol Craving Scale (PACS) were collected. Plasma Nectin-4 levels were measured at baseline before naltrexone treatment and week 4, week 8, and week 12 after the treatment Pearson’s correlation was used to analyze the relationship between baseline Nectin-4 and clinical variables, and repeated measures analysis was performed to assess the changes of Nectin-4 over time.

Results: Among the 201 participants, 122, 85, and 64 patients completed the week 4, week 8, and week 12 follow-up, respectively. The mean age of the AUD cohort was 44.4 ± 11.3 years, with an average duration of drinking history of 26.1 ± 11.7 years. At baseline, log-transformed plasma Nectin-4 levels were significantly positively correlated with age (r = 0.291, p < 0.01), years of education (r = -0.24, p < 0.01), smoking status (r = 0.157, p = 0.03), the duration of drinking history (r = 0.261, p < 0.01), the age of onset of severe AUD (r = 0.161, p = 0.03). No significant correlations were found between baseline Nectin-4 levels and depression (BDI), anxiety (BAI), or craving scores. Plasma Nectin-4 levels showed a significant increasing trend during the abstinence period, rising from 112.7 ± 38.8 pg/ml at baseline to 123.1 ± 40.6 pg/ml at week 4, 123.4 ± 36.8 pg/ml at week 8, and 129.3 ± 39.6 pg/ml at week 12 (p = 0.02).

Discussion & Conclusions: This study identified correlations between plasma Nectin-4 levels and clinical characteristics in patients with AUD, including history of alcohol use, smoking status, and the age of severe AUD onset. Notably, Nectin-4 levels significantly increased during the 12-week abstinence period. This elevation may reflect a restorative process of cell-cell integrity or a neuroadaptive response following alcohol cessation. Further research is needed to elucidate the underlying pathophysiological mechanisms of Nectin-4 dynamics in recovery from alcohol dependence.