Background: Recently published studies indicate that the Covid-19 pandemic has dramatically increased rates of anxiety, depression, and suicide in adolescents and young adults. Human and animal studies strongly indicate that early life stress leads to lasting changes to cognition and psychiatric outcomes, but less is known about how chronic adolescent stress may alter brain function across the lifespan. Methods: The current study examines the effects of chronic social instability stress (SIS) on male and female mice from 4 to 11 weeks of age. SIS mice (n=52) experienced twice weekly cage changes, preventing the formation of stable social hierarchies, while control mice (n=48) remained with their original cage mates. Mice were subsequently assessed throughout adulthood for changes in behavior associated with anxiety, affect, aggression, motivation, and recognition memory. At 66 weeks of age, levels hippocampal mRNA expression of genes associated with human early life stress were also compared (CRHR1, CRHR2, FKBP5, SLCA4). Results: Mice exposed to SIS showed decreased novel object recognition (p=0.002) and responded more during the progressive ratio task (p=0.033). At 66 weeks, SIS mice had increased hippocampal FKBP5 (p=0.03) and CRHR2 (p=0.005) expression relative to controls;furthermore, these measures negatively correlated with novel object recognition (FKBP: p=0.007;CRHR2: p=0.04). Conclusions: Chronic adolescent social instability stress led to persistent memory deficits and increased hedonic seeking in adulthood, possibly due to hippocampal damage resultant from lasting alterations to the stress cascade. Future studies will determine the cellular, molecular and circuit-level changes underlying these effects. Supported By: Support from an institutional grant from USC department of Psychiatry and Keck School of Medicine Keywords: Early Life Stress, FKBP5, Memory Deficit
Chronic Adolescent Social Instability Stress Leads to Impaired Recognition Memory and Increased Hippocampal FKBP5 and CRHR2 Expression in Adulthood