Previous studies identified several separate risk factors for stress-induced disorders. The authors of the present study tested whether they could use an integrated approach to predict susceptibility or resilience to social defeat stress (SDS) in mice and whether administration of acetyl-L-carnitine promoted resilience in the SDS paradigm.
Their findings identified multidimensional brain-body predictors of susceptibility versus resilience to SDS. The co-presence of anxiety, decreased hippocampal volume, and elevated systemic interleukin-6 characterized a susceptible phenotype that developed behavioral and neurobiological deficits after exposure to SDS. The susceptible phenotype showed social withdrawal and impaired transcriptomic-wide changes in the ventral dentate gyrus after SDS. At the individual level, a computational approach predicted whether a given animal developed SDS-induced social withdrawal, or remained resilient, based on the integrative in vivo measures of anxiety and immune system function. Finally, they provided initial evidence that administration of acetyl-L-carnitine promoted behavioral resilience in the SDS paradigm.
They feel that these results provide the starting point for in vivo models which predict development of neurobiological and behavioral deficits after stress exposure. This approach may lead to novel therapeutic strategies which promote resilience in susceptible individuals.
Nasca C, Menard C, Hodes Gm Bigio B, Pena C, Lorsch Z, Zelli D, Ferris A, Kana V, Purushothaman I, Dobbin J, Nassim M, DeAngelis P, Merad M, Rasgon N, Meaney M, Nestler EJ, McEwen BS and Russo SJ: Multidimensional Predictors of Susceptibility and Resilience to Social Defeat Stress. Biol. Psychiatry 86 (6): 483-491 (2019).