Transmitting Stress Response Patterns Across Generations

From a new study in Biological Psychiatry

Philadelphia, PA, November 4, 2013

Children of survivors of extremely stressful life events face adjustment challenges of their own, as has been most carefully studied among the children of Nazi Death Camp survivors. This "intergenerational" transmission of stress response has been studied predominately from the psychological perspective. However, recent research points to biological contributions as well.

Indeed, a new study just published in Biological Psychiatry demonstrates that offspring born to stressed mothers show stress-induced changes at birth, with altered behavior and gender-related differences that continue into adulthood.

"The notion that biological traits that are not coded by the sequence of DNA can be transmitted across generations is the focus of a field of research called epigenetics. This new paper implicates epigenetic regulation of a well-studied contributor to stress response, CRF1, in the intergenerational transmission of patterns of stress response," said Dr. John Krystal, Editor of Biological Psychiatry.

The researchers, led by Dr. Inna Gaisler-Salomon at University of Haifa in Israel, were interested in how stress modulates behavior and gene expression across generations. Previous studies in both humans and animals have shown that females exposed to stress even before they conceive can affect their children and even grandchildren.

In this study, they looked for a possible mechanism for these effects, focusing on the CRF1 gene. They studied adolescent female rats that went through a mild stress procedure before mating.

Stress led to an increase in CRF1 expression in the frontal cortex, a brain region involved in emotional regulation and decision making. Also, there was a dramatic increase in CRF1 expression in the egg cells of stressed females.

In the offspring of stressed female rats, brain CRF1 expression was increased as well, already at birth. "It seems that CRF1 is a marker molecule that tracks the stress experience across generations, perhaps via the germline, and maternal care is minimally involved in this particular effect," explained Gaisler-Salomon.

They also found behavioral differences between the offspring of stressed and non-stressed females, particularly in tests of emotional and exploratory behavior. Interestingly, CRF1 expression was increased in adult daughters of stressed females, but only if the offspring themselves were exposed to stress. This indicates that in adults, CRF1 expression depends on the mother's stress experiences in combination with the individual's stress experience and their sex.

"So why is this important?" asked Gaisler-Salomon. "Traditionally, it was believed that only genetic information is transferred from generation to generation via eggs and sperm cells. This study contributes to the notion that soft-wired information that is not written into the genetic code can also be transferred from one generation to the next via the germline."

Many psychiatric illnesses, such as schizophrenia and posttraumatic stress disorder, are related to stress. Better understanding of the related mechanisms can contribute to the development of better diagnostics and improved treatments.

The article is "Prereproductive Stress to Female Rats Alters Corticotropin Releasing Factor Type 1 Expression in Ova and Behavior and Brain Corticotropin Releasing Factor Type 1 Expression in Offspring" by Hiba Zaidan, Micah Leshem, and Inna Gaisler-Salomon (doi: 10.1016/j.biopsych.2013.04.014). The article appears in Biological Psychiatry, Volume 74, Issue 9 (November 1, 2013), published by Elsevier.

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Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Inna Gaisler-Salomon at +1 972 4824 9674 or igsalomon@psy.haifa.ac.il.

The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry
is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 4th out of 135 Psychiatry titles and 13th out of 251 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2012 Impact Factor score for Biological Psychiatry is 9.247.

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Media contact
Rhiannon Bugno
Editorial Office Biological Psychiatry
+1 214 648 0880
Biol.Psych@utsouthwestern.edu