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Chronic Social Instability Induces Anxiety and Defective Social Interactions Across Generations

      Background

      Chronic social instability during adolescence and early adulthood is known to produce a variety of long-lasting effects that may contribute to future psychiatric disorders. However, its potential to affect future generations has not been tested.

      Methods

      Female and male mice were exposed to chronic social stress involving social instability and disruption of social hierarchy from postnatal day 27 to 76. After treatment, a group of animals was used to evaluate long-term behavioral effects of the stress exposure, and other mice were used to generate F1, F2, and F3 offspring, to test for behavioral effects across generations.

      Results

      Chronic social instability during adolescence and early adulthood induces persistent behavioral alterations, including enhanced anxiety and social deficits that are transmitted predominantly to females across at least three generations. Both mothers and fathers can transmit all of these altered behaviors to their F1 offspring. However, only F1 fathers transmit all of them to their F2 and F3 daughters. In the F1 generation, enhanced anxiety and social deficits are associated with elevated serum corticosterone levels; however, in the F2 and F3 generations, they are not.

      Conclusions

      These findings support the idea that individual risk for psychiatric disorders that involve enhanced anxiety and/or social dysfunction may be dependent not only on the specific alleles of genes that are inherited from one's parents and on one's own experiences, but also on the experiences of one's parents when they were young.

      Key Words

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      Linked Article

      • Effects of Stress Across Generations: Why Sex Matters
        Biological PsychiatryVol. 73Issue 1
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          In this issue of Biological Psychiatry, Saavedra-Rodríguez and Feig (1) demonstrated that the experience of social stress during a period spanning from adolescence to adulthood induces long-term increases in anxiety-like behavior and social deficits in mice. However, the consequences of stress are revealed to extend far beyond this initial effect. Using a breeding design in which stress-exposed males and females are mated with stressed or nonexposed mice (Figure 1), with no subsequent stress exposure, the effects of stress across generations are explored.
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