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Effects of Stress Across Generations: Why Sex Matters

  • Frances A. Champagne
    Correspondence
    Address correspondence to Frances A. Champagne, Ph.D., Department of Psychology, Columbia University, 1190 Amsterdam Ave, Room 406, Schermerhorn Hall, New York, New York 10027
    Affiliations
    Department of Psychology, Columbia University, New York, New York
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      In this issue of Biological Psychiatry, Saavedra-Rodríguez and Feig (

      Saavedra-Rodríguez L, Feig LA (2013): Chronic social instability induces anxiety and defective social interactions across generations. Biol Psychiatry 73:44–53.

      ) 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. Offspring (F1), grandoffspring (F2), and great-grandoffspring (F3) were observed to inherit the effects of parental (F0) stress, with females but not males exhibiting anxiety-like behavior and social deficits. Although males do not inherit the behavioral characteristics associated with stress exposure, the breeding design suggested that it is through males (and not females) that these effects can be transmitted to the F3 generation. Both mothers and fathers are capable of the transmission of the effects of social stress to their daughters; however, beyond this F1 generation, it is through stress-exposed fathers that both anxiety and social deficits can be observed in subsequent generations. This study highlights the complex pathways through which males and females may potentially influence the development of future generations and may contribute to a growing literature on the transgenerational consequences of adversity (
      • Franklin TB
      • Russig H
      • Weiss IC
      • Graff J
      • Linder N
      • Michalon A
      • et al.
      Epigenetic transmission of the impact of early stress across generations.
      ).
      Figure thumbnail gr1
      Figure 1Summary of research design and transgenerational effects reported by Saavedra-Rodríguez and Feig
      (

      Saavedra-Rodríguez L, Feig LA (2013): Chronic social instability induces anxiety and defective social interactions across generations. Biol Psychiatry 73:44–53.

      )
      . (A) In this study, stressed (S) males and females (SF0♂, SF0♀) were mated to generate stressed F1 offspring. F1 offspring were then either mated with control (C; nonstressed) mice or F1 offspring of stressed mice to generate the F2 generation. F2 mice were then mated with either the F2 descendants of stressed mice or with controls to generate the F3 generation. Blue square indicates an observed increase in anxiety-like behavior (relative to control mice), whereas a red circle indicates deficits in social behavior. (B) Summary of the transmission of the effects of social stress to F1, F2, and F3 generation females (male phenotype was not altered). Through the matriline, increased anxiety-like behavior is observed through to the F1 generation (social deficits persist until the F2 generation). Conversely, in the patriline, anxiety-like behavior and social deficits persist to the F3 generation. S, stressed; SF0♂, stressed males; SF0♀, stressed females; C, control; F1, offspring; F2, grandoffspring; F3, great-grandoffspring.
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