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Study shows downregulated gene expression in prefrontal cortex of PTSD patients

Analysis of postmortem samples of the prefrontal cortex of individuals with PTSD showed decreased expression of serum and glucocorticoid regulated kinase 1, suggesting altered expression may contribute to behavioral phenotypes associated with traumatic stress.

“Improper functioning of the brain regions known as prefrontal cortex and amygdala is associated with the development of [PTSD]. However, little is known about the molecular mechanisms that underlie this condition,” Pawel P. Licznerski, PhD, of Yale University School of Medicine, New Haven, Connecticut, and colleagues wrote.

To identify transcriptional alterations that contribute to PTSD in the prefrontal cortex, researchers conducted a whole genome array of postmortem prefrontal cortex samples from six individuals with PTSD and six age-matched controls with no psychiatric diagnoses.

The microarray study identified 231 downregulated and 42 upregulated genes in the prefrontal cortex among individuals with PTSD.

Serum and glucocorticoid regulated kinase 1 (SGK1) was one of the most highly dysregulated genes, downregulated by more than 80% in individuals with PTSD compared with controls. SGK1 was been reported to be induced by corticosteroid hormones and has been implicated in cellular responses to stress, according to researchers.

SGK2 and SGK3 expression levels were also decreased among individuals with PTSD compared with controls, though microarray results were not significant.

Quantitative polymerase chain reaction analysis confirmed microarray findings that showed significantly decreased expression levels of SGK1, SGK2 and SGK3 in individuals with PTSD compared with controls.

Researchers examined several other proteins regulated by stress and glucocorticoids and found only the glucocorticoid receptor DNA binding factor I was significantly different in the prefrontal cortex of individuals with PTSD compared with controls.

“In summary, the results of this study demonstrate that SGK1 expression is decreased in the postmortem [prefrontal cortex] of a small cohort of PTSD subjects, a finding that must be confirmed in additional PTSD subjects,” the researchers wrote. “In addition, studies are currently underway to examine levels of SGK1 in the blood cells of PTSD patients as well as to test for association of SGK1 polymorphisms in PTSD. It is possible that SGK1 may serve as a potential clinical biomarker for PTSD, as recently described for pituitary adenylate cyclase-activating polypeptide, which was also shown to contribute to behavioral changes observed in [learned helplessness].” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.