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Study Finds Parental Stress Triggers Depression Related Immune Changes Across Generations

An individual’s physical and behavioral traits are typically attributed to the genetic information inherited from parents and the preceding generations. However, more recent evidence suggests it is a combination of environmental factors as well as genetics. The opportunity exists during gestation, as well as through the mother-infant interaction after birth, for a mother’s behavior to influence the development of behavioral characteristics in offspring. In particular, social stressors associated with postpartum depression and anxiety have long-term physiological and behavioral effects on children as well as future generations, and there is growing evidence that these effects may be mediated by the immune system.

Ben Nephew, PhD, a behavioral neuroscientist in the Department of Biomedical Sciences at Cummings School of Veterinary Medicine at Tufts University, has developed an innovative rodent model of stress-induced postpartum depression and anxiety. His model is based on creating chronic social stress for a maternal rat by introducing a male rat into her cage for a short time each day. The male rat’s presence creates conflict given his interest in mating and prompts the mom to become aggressive towards the male and less attentive to her pups even when the male is not present. He uses behavioral observation, physiological monitoring, molecular genetics, neuroendocrine manipulation and MRI to investigate the impact of this social stress.

His research reveals that the nature of the maternal care received by an infant early in life can trigger immune and hormonal abnormalities that may impact the development of disorders associated with changes in the immune system, including depression and anxiety. More specifically, data reveal that the impact is not only in the first generation but also in generations that follow, suggesting that genetic and environmental impacts persist and could accumulate across time. There are also sex-specific changes in the immune and hormonal profiles of offspring exposed to stress, suggesting that the offspring’s sex could affect the efficacy of potential treatments for immune mediated disorders.

Collaboration has been key to enhancing Nephew’s research efforts. Whether the Nephew Lab is collaborating with Chris Murgatroyd, PhD, a genetic-environmental researcher from Manchester Metropolitan University, England, Kristina Deligiannidis, MD, a postpartum clinician at UMass Medical School, or Gillian Beamer, VMD, PhD, DACVP, a pathologist at Cummings School Department of Infectious Disease and Global Health, Nephew credits his colleagues as having played a significant role in bringing new insights to his research.

Nephew is currently exploring the use of intranasal vasopressin and oxytocin, key hormonal regulators of social behavior, as treatments for postpartum depression and anxiety as well as the development of early life stress associated depression and anxiety behaviors in offspring. In addition, working with Deligiannidis and other collaborators at UMass Medical School, Nephew is looking at the potential impact of birth induction on rates of postpartum depression and anxiety using medical record databases.

Nephew’s research model mimics social stress in a family that adversely affects maternal behavior. As a result, it is breaking ground in the testing of novel preventative measures and treatments for a growing number of human immune-related disorders, such as depression, anxiety, allergies, asthma and responses to infections and vaccinations. “Our goal is to be able to intervene early and take care of maternal mental health with the hopes of preventing depression and anxiety and related disorders in offspring and future generations as well,” says Nephew.