155: Novel Gut-Brain Axis for Craving, Alcohol Withdrawal & Withdrawal-Associated Depression in Patients With Alcohol Use Disorder

Statement of Purpose: Alcohol use disorder (AUD) patients exhibit domains such as alcohol withdrawal, depression and craving. The gut-immune response may play a significant role in expressing these AUD domains. This study examined the role of intestinal permeability, pro-inflammatory cytokines and hormones levels on the AUD domains.

Description of Methods & Materials: Forty-eight AUD patients [male (n=34) and female (n=14)] aged 23-63 yrs. were grouped categorically using the Clinical Inst Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score >10] Gr.1 [n=22]), and clinically not-significant group (NCS-CIWA [score≤10] Gr.2 [n=26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing pro-inflammatory cytokines, and hormones and markers of intestinal permeability) were analyzed (Table 1). A sub-set of 13 AUD patients were assessed for craving response towards drug-seeking using Penn-Alcohol Craving Score (PACS).

Data & Results: Gr.1 (CS-CIWA group) patients exhibited unique and significantly higher levels of adiponectin and IL-6 compared to Gr.2 (NCS-CIWA). Across groups, there were robust association of higher, and significant effects of association on the measures in the withdrawal domain with gut-immune markers (LPS, adiponectin, IL-6 and IL-8); and associations of withdrawal-associated depression domain with (LPS, sCD14, IL-6 and IL-8). Craving (assessed by PACS, Penn-Alcohol Craving Scale) was significantly associated with could be described by the gut-dysregulation (LBP and Leptin) and candidate proinflammatory (IL-1β and TNF-α) markers (Figure 1a). Such pathway model describes the heavy drinking phenotype, HDD90 with very even higher effects (R²=0.955, p=0.006) in the AUD patients, who had higher ratings for craving (PACS >5) (Figure 1b).

Interpretation, Conclusion or Significance: Interaction of gut-dysfunction, cytokines involved in both inflammation and mediating-chemotactic activity constitutes a novel pathophysiological gut-brain axis for withdrawal and withdrawal-associated depression and craving domains in AUD. AUD patient with higher craving show higher reinforcing effects of the gut-brain axis response for heavy drinking.

Disclosures: None