Nasca C, Menard C, Hodes G, et al. - In view of previous works revealing several separate risk factors for stress-induced disorders, researchers sought to assess whether 1) integrative brain-body behavioral, immunological, and structural domains characterize and predict susceptibility or resilience to social defeat stress (SDS) in mice and 2) resilience at the SDS paradigm is promoted with administration of acetyl-L-carnitine. Multidimensional brain-body predictors of susceptibility vs resilience to SDS were identified. Susceptible phenotype that developed behavioral and neurobiological deficits after exposure to SDS was characterized by the copresence of anxiety, decreased hippocampal volume, and elevated systemic interleukin-6. They noted social withdrawal and impaired transcriptomic-wide changes in the ventral dentate gyrus in the susceptible phenotype following SDS. Based on the integrative in vivo measures of anxiety and immune system function, a computational approach predicted whether a given animal developed SDS-induced social withdrawal, or remained resilient at the individual level. Finally, initial evidence was gained indicating promotion of behavioral resilience at the SDS paradigm following administration of acetyl-L-carnitine.