Identifying a Brain Mechanism that Promotes – or Hinders – Resistance to Stress

Susan K. Wood, Ph.D., Assistant Professor at the University of South Carolina School of Medicine, Expert on depression and anxiety
Susan K. Wood, Ph.D.

Susan K. Wood, Ph.D., Assistant Professor at the University of South Carolina School of Medicine used her 2010 NARSAD Young Investigator Grant to study brain mechanisms underlying both the vulnerability and resistance to stress that can lead to the manifestation of psychiatric illness. The lead author of a study published in the June 1st issue of the journal Biological Psychiatry, Dr. Wood conducted the study under team leader Rita J. Valentino, Ph.D., at the Children’s Hospital of Philadelphia, a 2002 NARSAD Distinguished Investigator Grantee and other colleagues.

Using an animal model to conduct the research, the researchers found that rats subjected to repeated social stress divided almost evenly in two groups depending on their coping strategy. One group showed proactive behavior after being exposed repeatedly to the same “social defeat” stress (which models the human response to being dominated or intimidated). The other group responded to the same stress passively, accepting domination. Not surprisingly, members of the latter group were more susceptible to depression-like behavior.

To identify the mechanisms underlying the different coping strategies, the team focused in on activity in a part of the brain called the dorsal raphe nucleus, known to be a prime source of the neurotransmitter serotonin. Low serotonin levels have long been linked with depression; antidepressants like Prozac® keep serotonin levels in the brain elevated. In this study, the researchers identified a cellular mechanism, or adaptive response to stress in the brain, that involves a redistribution of receptors for the stress neurohormone, CRF (corticotropin-releasing factor) in the dorsal raphe nucleus in serotonin neurons.

When the redistribution process of CRF receptors is functioning, serotonin neurons are activated and the animals show proactive behavior; when it is not functioning properly, serotonin neurons are inhibited and the animals demonstrate depressive-like behavior. Further research is required to determine how this translates in the human brain, but the identification of a cellular mechanism for individual differences in stress responses and consequences may open a new avenue for development of more effective interventions.

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