Introduction: Structural alterations in cortical thickness and the microstructural organization 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. Materials and Methods: Thirty-four BD-I (DSM-IV-TR) and 38 healthy controls (HC) underwent T1 and diffusion-weighted magnetic resonance imaging scanning, and the Alcohol Use Disorders Identification Test-Consumption to assess alcohol use. Connectomes comprising 34 cortical and 9 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 the 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 it 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 ± standard deviation 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 the susceptibility to an increased risk of relapse in the disorder. Impact statement The association between non-dependent alcohol use and neural architecture in bipolar disorder (BD) is unknown, despite the poor clinical trajectory and increased likelihood of relapse associated with alcohol use in BD. We demonstrate that together alcohol and a diagnosis of BD is associated with a subnetwork involving nodes of the cortico-limbic and reward networks. This subnetwork, demonstrated in BD and absent in controls, differentially involves nodes that are specific to reward and emotion processes. This suggests a diagnosis-specific biological vulnerability for alcohol use and may be consistent with known mood lability and thus relapse associated with alcohol use in BD.
Keywords: alcohol; bipolar disorder; structural network connectivity; subnetwork analysis.