Editors' ChoiceNEUROPSYCHIATRIC DISEASE

Inheritance of fear and trauma

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Science Translational Medicine  26 Aug 2015:
Vol. 7, Issue 302, pp. 302ec145
DOI: 10.1126/scitranslmed.aad1822

Although Lamarckism, the belief that an organism can pass on characteristics that it acquired during its lifetime to its offspring, lost acceptance decades ago, it has recently enjoyed a resurgence via observations of epigenetic inheritance. For example, studies have shown that when mice are taught to fear an odor, both their offspring and the next generation are born fearing it. Although parental exposure to stress is typically believed to increase vulnerability in offspring of rodents and humans, some biological alterations in progeny may instead reflect an accommodation to parental trauma.

Yehuda et al. obtained blood samples from 32 Holocaust survivors and found a 10% increase in DNA cytosine methylation within the third glucocorticoid response element (GRE) of FKBP5 intron 7. This intron was tested because it can fold to contact the transcription start site; this region can be demethylated by glucocorticoid administration; and methylation of this GRE affects FKBP5 expression. Unexpectedly, among 22 offspring born from Holocaust survivor parents, the findings were reversed: DNA cytosine methylation at the same site within FKBP5 was decreased by 8%. This represents the first human finding of pre-conception stress resulting in epigenetic changes in both exposed parents and their offspring, although in opposite directions. Because both parents of each offspring were Holocaust survivors, the mechanism of inheritance cannot be resolved here; further studies investigating families in which only one parent was exposed to such trauma may enhance our understanding.

If it can be shown that the extent of FKBP5 methylation in PTSD patients correlates to prognosis, this work may ultimately help identify a biomarker of PTSD risk; moreover, if FKBP5 activity proves to affect clinical outcome, this protein may represent a therapeutic point of intervention. In the offspring of highly traumatized individuals, testing of FKBP5 methylation may facilitate interventions to prevent intergenerational transmission of trauma.

R. Yehuda et al., Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol. Psychiatry 10.1016/j.biopsych.2015.08.005 (2015). [Abstract]

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