Stem Cell Study Provide New Information of Post-Traumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a syndrome resulting from exposure to real or threatened serious injury or sexual assault. The signs and symptoms of PTSD appear to arise from complex interactions of psychological and neurobiological factors. Studies have found alterations in the amygdala, prefrontal cortex, hippocampus, and anterior cingulate, and corpus callosum as well as altered functioning of the hypothalamic pituitary axis (HPA).

The psychological problems of soldiers in World War II, the Korean War, and the Vietnam War, along with the severe psychological impact of rape, fostered interest and research in the collection of symptoms that became known as posttraumatic stress disorder. PTSD was first included in the Diagnostic and Statistical Manual of Mental Disorders in 1980 when DSM-III was published. The diagnostic criteria have undergone significant revisions with DSM-IV and DSM-5. 

Signs and symptoms

Symptoms of posttraumatic stress disorder (PTSD) include the following:

• Persistent re-experiencing of the event: intrusive thoughts related to the traumatic event, nightmares or distressing dreams, persistent or recurrent involuntary memories, dissociation (including flashbacks) and intense, negative emotional or physiological reaction on exposure to reminders (traumatic triggers)
• Avoidance of traumatic triggers or of thinking/talking about the experience
• Negative alterations in cognition and mood: inability to recall important aspects of the trauma; persistent negative beliefs and expectations about oneself, others, and the world; inappropriate blaming of oneself for the trauma; irritability, problems with sleep or concentration, increased startle reaction, increased vigilance for potential danger, self-harming acts, or recklessness

One cannot diagnose PTSD until one month has passed since the traumatic incident. Acute stress disorder, which has similar symptoms, is diagnosed during the first month.

Stem cell-derived neurons from combat veterans with post-traumatic stress disorder (PTSD) react differently to a stress hormone than those from veterans without PTSD

Reprogramming cells into induced pluripotent stem cells is like virtually taking cells back in time to when they were embryonic and had the ability to generate all the cells of the body. “These cells can then be differentiated into neurons with the same properties as that person’s brain cells had before trauma occurred to change the way they function. The gene expression networks from these neurons reflect early gene activity resulting from genetic and very early developmental contributions, so they are a reflection of the ‘pre-combat’ or ‘pre-trauma’ gene expression state.

To mimic the stress response that triggers PTSD, the scientists exposed the induced pluripotent stem cell-derived neurons to the stress hormone hydrocortisone, a synthetic version of the body’s own cortisol that is used as part of the “fight-or-flight” response.

Using gene expression profiling and imaging, the scientists found that neurons from individuals with PTSD were hypersensitive to this pharmacological trigger. The scientists also were able to identify the specific gene networks that responded differently following exposure to the stress hormones.

The team’s gene expression analysis revealed a set of genes that were particularly active in PTSD-prone neurons following their exposure to stress hormones.

Importantly, the gene signature that they found in the neurons was also apparent in brain samples from deceased individuals with PTSD, which tells us that stem cell models are providing a pretty accurate reflection of what happens in the brains of living patients. Moreover, the distinctions between how PTSD and non-PTSD cells responded to stress could be informative in predicting which individuals are at higher risk for PTSD.

The researchers plan to continue leveraging their induced pluripotent stem cell models to further investigate the genetic risk factors pinpointed by this study and to study how PTSD affects other types of brain cells, helping to broaden opportunities for therapeutic discovery.

SOURCE:

Seah, C., Breen, M.S., Rusielewicz, T. et al. Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression. Nat Neuroscience. Retrieved from : https://www.nature.com/articles/s41593-022-01161-y 

IMAGE:Photo by Benjamin Faust on Unsplash.