LAUSR

INTRODUCTION Structural alterations in cortical thickness and the microstructural organisation of white matter are independently associated with non-dependent alcohol consumption and bipolar disorder(BD). Identifying their interactive and network level effects on brain topology may identify the impact of alcohol on reward and emotion circuitry, and its contribution to relapse in BD. METHODS Thirty-four BD-I (DSM-IV-TR) and 38 healthy controls underwent T1 and diffusion-weighted MRI scanning, and the AUDIT-C to assess alcohol use. Connectomes comprised of 34 cortical and nine subcortical nodes bilaterally (Freesurfer v5.3) connected by fractional anisotropy-weighted edges derived from non-tensor based deterministic constrained spherical deconvolution tractography (ExploreDTI v4.8.6) underwent permutation-based topological analysis (NBS v1.2) and were examined for effects of alcohol use and diagnosis-by-alcohol use accounting for age, sex and diagnosis. RESULTS Alcohol was significantly related to a subnetwork, encompassing connections between fronto-limbic, basal ganglia and temporal nodes (Frange=5-8.4, p=0.031) and was not detected to have an effect on global brain integration or segregation. A portion of this network (18%), involving cortico-limbic and basal ganglia connections, was differentially impacted by alcohol in the BD relative to the control group (Frange=5-8.8, p=0.033), despite the groups' consuming similar amounts of alcohol (BD: mean±SD 4.95±3.0; HC 3.62±3.0, T=1.88, p=0.06). DISCUSSION Non-dependent alcohol use impacts brain architectural organization and connectivity within salience, reward, and affective circuitry. The relationship between alcohol use and topology of the network in BD suggests an interactive effect between specific biological vulnerability and alcohol use, which may explain susceptibility to increased risk of relapse in the disorder.