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.
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.
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.