People with post-traumatic stress disorder (PTSD) have reduced activity of the protein serum and glucocorticoid regulated kinase 1 (SGK1) in their prefrontal cortices, and experimentally reducing the protein's activity in rats leads to PTSD-like behavior, according to a new study in PLOS Biology. The study by Pawel Licznerski, Ronald Duman and colleagues of the Department of Psychiatry at Yale University publishing in the Open Access journal PLOS Biology on Oct. 27th, suggests that augmenting activity of SGK1 may be therapeutic in PTSD.
Performing a whole-genome expression screen on the post-mortem brains of six subjects with PTSD, the authors found that expression of SGK1 was reduced in the prefrontal cortex by over 80% compared to controls. The subjects studied were part of a PTSD brain bank, the first of its kind, established by the authors. To understand the cellular mechanisms at work, the authors turned to rats, and showed that those rats with lower SGK1 activity had higher levels of learned helplessness in response to a shock (a behavior thought to mimic one aspect of PTSD). Experimentally reducing SGK1 activity in rats induced learned helplessness, while overexpressing the protein reduced it. Reducing SGK1 activity also induced several other PTSD-like behaviors, and caused cellular changes in prefrontal cortical neurons consistent with an augmented fear response.
Together, these results indicate that a reduction in SGK1 activity likely contributes to PTSD. Larger postmortem studies will be needed to confirm these findings, but if they are borne out, SGK1 or other proteins with which it is linked may provide new targets for medications to reverse the effects of PTSD, which, according to the Veterans Administration, affects over 5% of the United States population, and over 10% of veterans.
Source for the prevalence of PTSD:http://www.ptsd.va.gov/professional/PTSD-overview/epidemiological-facts-ptsd.asp "The lifetime prevalence of PTSD among men was 3.6% and among women was 9.7%" "the authors estimated the prevalence of PTSD among the total Gulf War Veteran population to be 10.1%" "Among the 1,938 participants, the prevalence of current PTSD was 13.8%."
Please mention PLOS Biology as the source for this article and include the links below in your coverage to take readers to the online, open access articles
All works published in PLOS Biology are open access, which means that everything is immediately and freely available.