Novel paradigms for the gut–brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder

• Published in: Frontiers in psychiatry Vol. 14; p. 1203362
• Main Authors: Vatsalya, Vatsalya, Verster, Joris C., Sagaram, Manasa, Royer, Amor J., Hu, Huirong, Parthasarathy, Ranganathan, Schwandt, Melanie L., Kong, Maiying, Ramchandani, Vijay A., Feng, Wenke, Agrawal, Ruchita, Zhang, Xiang, McClain, Craig J.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.09.2023
• Subjects: alcohol dependence (AD); alcohol use disorder (AUD); craving; cytokines; depression; gut–brain axis; Psychiatry; alcohol dependence (AD); craving; heavy drinking; gut–brain axis; alcohol use disorder (AUD); cytokines; depression; withdrawal
• ISSN: 1664-0640; 1664-0640
• DOI: 10.3389/fpsyt.2023.1203362

Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Forty-eight AUD patients [men ( = 34) and women ( = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [ = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [ = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R = 0.955, = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. ClinicalTrials.gov, identifier: NCT# 00106106.