Early abstinence in severe alcohol use disorder: MCP-1 decline, choroid plexus shrinkage, and region-specific grey-matter volume changes

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Abstract
In this longitudinal study, 37 patients with severe alcohol use disorder (SAUD) were tested at the beginning (T1) and end (T2) of withdrawal to explore the evolution of and relationship between systemic inflammation, volumetric changes for brain grey matter (GM) and choroid plexus (ChP), and clinical symptoms. At T1, patients exhibited high levels of anxiety, depression, and craving, and had elevated plasmatic pro-inflammatory cytokines, indicating low-grade systemic inflammation. MCP-1 levels correlated positively with ChP volume and severity of withdrawal symptoms, while MIP-1β also correlated with ChP volume, together suggesting an acute immune response at T1, and underscoring the ChP as a potential neuroimmune biomarker. During three weeks’ abstinence, IL-8, MIP-1β, and MCP-1 levels decreased, although MIP-1β did not return to control levels, and TNF-α showed no significant reduction. Volumetric MRI analyses suggested two concurrent trajectories during withdrawal. First, an overall “recovery‐driven” pattern of rapidly increasing grey matter (GM) volume in widespread forebrain regions with parallel declines in ventricle size and craving. Second, GM in limbic cortical areas, temporal and inferior frontal cortex showed no significant volumetric gain. However, these regional volumes correlated significantly with declining MCP‐1, indicative of a “deflation”, potentially related to declining microglial activation. These findings highlight the role of inflammatory processes in shaping early neuroplastic changes during withdrawal and point to a central role of MCP‐1 in inflammation-driven morphometric changes.

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