Gene regions linked to PTSD

A study of more than 165,000 US military veterans has found eight gene regions linked to post traumatic stress disorder (PTSD), including one involved in the release of the stress hormone cortisol.

The researchers, led by Joel Gelernter of the Yale University School of Medicine in New Haven, US, analysed data from the Million Veterans Program, a US government initiative that aims to link the genes of a million returned service personnel with data on their military service, lifestyle and health.

PTSD is characterised by recurrent bouts of intense fear in the setting of a prior traumatic event, such as a physical or sexual assault, car crash or the experience of war. 

The lifetime prevalence of PTSD in US adults is just under 7%. In veterans, however, lifetime prevalence rises to a disturbing 31% for males and 27% for females.

The team homed in on three classic symptoms of PTSD: reliving the event through intrusive memories or nightmares, often with sweating, palpitations and a sense of panic; being “hyperaroused” and on constant alert for danger, which disturbs sleep and concentration; and avoidance of people, places and even thoughts that might trigger memory of the event.

Eight genetic locations had links to those symptoms and, crucially, two of those coded for proteins involved in the release of cortisol. Cortisol is a hormone that goes up in response to stress and can strengthen memory of traumatic events.

The researchers also found overlap between the genetic changes of PTSD and those for a range of other mental health conditions, including depression and schizophrenia.

The link with schizophrenia, they note, is of particular interest owing to similarities between the “re-experiencing” symptoms of PTSD and the hallucinations of schizophrenia.

“Psychotic symptoms, per se, occur in some patients with PTSD and, even more broadly, among individuals exposed to traumatic events,” they write.

“Auditory hallucinations occur not only in schizophrenia but also in trauma-related disorders such as borderline personality disorder and, notably, PTSD.”

And those linkages may be explained by another effect of the identified genes.

They are expressed in several brain regions, including the brain’s “alarm system”, the amygdala, and an area called the striatum, where changes in the chemical messenger dopamine have been implicated in schizophrenia symptoms.

“The finding of an association with striatal…. neurons, coupled with the aforementioned genetic correlation between re-experiencing symptoms and schizophrenia, should spur further investigations into a role for striatal dysfunction in PTSD,” the authors write.

But there were also associations with physical illness, and one in particular that might explain a curious treatment for PTSD.

The blood pressure drug Prazosin has been used to treat the nightmares of PTSD and, indeed, PTSD and high blood pressure often co-occur.

The researchers found that re-experiencing symptoms were linked to hypertension in what may be understood as a “shared genetic risk”.

It is a link, they argue, that could further refine treatment options for people with the devastating disorder.

“Stratifying those patients with PTSD with increased polygenic risk for hypertension might identify a subgroup who are especially responsive to the anti-PTSD effects of prazosin,” they write.

The study appears in the journal Nature Neuroscience.