Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior.

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Chronic stress is a significant risk factor for human anxiety disorders, yet not all individuals exposed to stress develop a clinically relevant anxiety symptomatology. The underlying reasons for these differences are not yet fully understood but involve an interaction of complex genetic and environmental factors that vary among individuals resulting in stress susceptibility or resilience. The chronic social defeat stress (CSDS) model is a well-established mouse paradigm of psychosocial stress, with construct, face, discriminative, and predictive validity for stress-related disorders. It involves 10 days of brief daily confrontation of two conspecific male mice, a resident-aggressor and an intruder who reacts with defensive, flight, or submissive behavior Although all defeated mice experience stressful stimuli, only some develop stress-related symptoms, measured as social avoidance, making it an excellent model to investigate mechanisms associated with susceptibility and resilience. We have previously shown that genetic factors strongly affect the behavioral outcome of the CSDS, since different inbred mouse strains vary in the proportion of susceptible and resilient animals as well as in their stress coping behaviors.

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