Operation PTSD

Posted by Donovan Cronkhite on July 18, 2024 in Attention, Behavioral Neuroscience, Biomarkers, Cognition, Culture, Decision-Making, depression, Development, Emotions, Executive function, genetics, Memory, Mental Illness, Mood, Neurological Disorders, Neuroscience, Neuroscience Phenomena, NeuWrite, News, Politics, Science communication, Stress, Uncategorized | 1 Comment

The full-scale invasion of Ukraine that started in 2021 has had devastating impacts on the daily lives of those in Ukraine, and this includes a dramatic increase in those suffering from PTSD in this war-torn country. Although 2021 was not the beginning of the tensions between Russia and Ukraine (1), as the war rages on, the rate only increases; in 2023, the incidence was almost four times that of 2021 (2). As stated by one researcher, Viktor Dosenko, “PTSD is one of the most important medical problems in Ukraine” (V. Dosenko, personal communication, June 19th, 2024).  That’s why researchers from the National Academy of Sciences (NAS) of Ukraine, in Kyiv, Ukraine, including Dosenko, saw it as crucial to investigate more accurate ways to diagnose PTSD, as current diagnostic criteria can be rather subjective. 

PTSD Basics

Post Traumatic Stress Disorder, or PTSD, can occur after someone suffers a traumatic event, life-threatening or not (V. Dosenko, personal communication, June 19th, 2024), and there are a range of different social, psychological, and biological factors that play a role in the development of PTSD (3).  People who have previously experienced traumatic events are more susceptible; however, this is not the only at-risk population. Some other groups that have shown an increased likelihood of experiencing PTSD include women, people with a family history of mental illness, younger populations, and those with lower levels of education.  Although not everyone develops PTSD after experiencing a traumatic event, it is still possible for anyone to experience PTSD after witnessing a traumatic event.

People who do go on to develop PTSD can experience the disorder in many different ways. Although the media tends to sensationalize PTSD as a disorder characterized by intense flashbacks of a traumatic event, this is not all that there is to PTSD. Along with the intrusive thoughts of reliving the traumatic event, individuals who suffer from PTSD may have avoidant behaviors (avoiding situations that may trigger thoughts that make them relive the event), problems with the memory of and/or distorted thoughts about the event that triggered their PTSD, and even irritability and problems with concentration.

However, what it really means for someone to suffer from PTSD is not only the symptoms but also the duration of symptoms: according to the World Health Organization (WHO), “…symptoms must last for more than a month and must cause significant distress or problems in the individual’s daily functioning,” for someone to be diagnosed with PTSD (3). However, an assessment of these symptoms is rather subjective, usually left up to the judgment of a psychiatrist based on their experience, and not an objective test or biological indicator. This is where neuroscience and the study of the brain’s response to trauma come in.

There are differences in brain function that those with PTSD experience that could be used to help more accurately diagnose PTSD. These differences include hyperactivity of the amygdala (a structure responsible for our emotional responses, most notably fear) and a decrease in the activity seen in the prefrontal cortex (PFC; a region responsible for rational thinking, decision-making, and attention, among other things) (4). These two structures interact with the hippocampus, the structure associated with memory creation and consolidation, and it is also affected by the development of PTSD, most apparently in the intense flashbacks individuals experience. In fact, research has found that hippocampal volume was most affected in PTSD as compared to the 8 other structures that were studied (5,6,7,8) Additionally, increased PTSD symptom severity was associated with decreased hippocampal volume (9).

The symptoms that distinguish PTSD from trauma responses can easily be explained by the alterations of these structures. However, these alterations are not enough to accurately diagnose all cases of PTSD. Because many other disorders share symptoms and neurological irregularities with PTSD (such as anxiety disorders, depression, and substance use disorders; 3), having ways to more accurately diagnose PTSD is crucial, which is imperative to getting people the treatment they need. As of yet, the molecular mechanisms underlying PTSD remain unknown. However, the researchers from NAS Ukraine wanted to change that, as these could serve as biomarkers to objectively diagnose PTSD. 

Biomarkers: the key to PTSD?

Biomarkers are molecular indicators that can be used to identify a variety of biological processes, including those of diseases and disorders. In fact, biomarkers are especially important for disordered functions because they can sometimes be our only indicator that something is amiss (10). In some cases, they are required for an official diagnosis; sometimes they simply make it easier to diagnose a condition earlier on. When it comes to PTSD, finding a biomarker would make it easier for patients who suffer from PTSD to obtain an official diagnosis and get the treatment they need to improve their quality of life. Seeing the potential benefit this could bring to so many people around the world, especially with the catastrophic rates of PTSD in Ukraine right now, Klimenko et al. (2024) from the NAS of Ukraine were interested in identifying some of these secret indicators by looking at some of the basic units of life: RNA. 

Most people have heard of DNA as the basic building block of life, and of course, it is. However, it does not act alone, and its partner in crime (so to speak), RNA, can be just as important as DNA for potential therapeutic applications (11). DNA, or deoxyribose nucleic acid, is a genetic structure in the shape of a double helix (see image to right) that contains all of the genetic information of an organism (12). This genetic code is like a set of instructions for the body to carry out its functions. Conversely, RNA, or ribose nucleic acid, is only a single-stranded structure that, rather than storing genetic information, carries out the instructions stored in DNA to produce proteins and perform cellular processes in the body (13). The class of RNAs that perform cellular processes in the body, and do not provide information for translation into proteins, are known as non-coding RNA (ncRNA). Researchers Klimenko et al. (2024) were interested in understanding how a few of these ncRNA strands are affected in the development of PTSD, specifically in the hippocampus.

Researchers from NAS of Ukraine found that three ncRNAs, in particular, showed a significant decrease in expression in the hippocampus. Since ncRNAs regulate a large number of genes involved in many pathological conditions, they could potentially be used as biomarkers for a wide range of illnesses; this includes stress-related psychological disorders, such as PTSD. Thus, these three ncRNAs are what could serve as biomarkers for the diagnosis of PTSD, as ncRNAs can be measured non-invasively in biofluids (blood, urine, etc; 14).  Furthermore, this research also suggests that once exact numerical values of these RNA biomarkers are determined to accurately diagnose PTSD, they could also be a potential target for gene therapy (cite). Thus, this may be the key to PTSD.

CONCLUSION

Globally, it is estimated that 3.9% of the population experiences PTSD at some point in their lives (cite). With such crippling symptoms and impacts on people’s quality of life, the need for effective treatment for PTSD is ever-present. This is especially true in Ukraine, where it is predicted the prevalence of PTSD may eventually reach 32-40% of the population (Klimenko et al. 2024). The first step to getting people the treatment they need, however, is an accurate diagnosis; the discovery of biomarkers for PTSD can make that a whole lot easier.

ACKNOWLEDGMENTS
This article was written in collaboration with the team at Science at Risk, a digital platform and community of Ukrainian scientists that strive to help Ukrainian scientists suffering from the war to be heard and visible in the world, as well as to contribute to the preservation and restoration of Ukrainian science. A special thanks to Diana Siarki, a member of the communication team at Science at Risk, and Viktor Dosenko, a Ukrainian researcher who contributed to this research and was kind enough to answer my questions for this article.

References

1. https://en.wikipedia.org/wiki/Russian_invasion_of_Ukraine#:~:text=On%2024%20February%202022%2C%20Russia,country%20since%20World%20War%20II.
2. https://unn.ua/en/news/significant-increase-in-ptsd-cases-in-ukraine-almost-4-fold-increase-in-2023-compared-to-pre-war-levels
3. https://www.who.int/news-room/fact-sheets/detail/post-traumatic-stress-disorder#:~:text=Around%2070%25%20of%20people%20globally,in%20their%20lives%20(2)
4. https://www.scielo.br/j/pn/a/GKts3pH37RfNMHpcQKLbV6b/?lang=en
5. https://journals.lww.com/hrpjournal/abstract/2022/03000/does_hippocampal_volume_in_patients_with.3.aspx?context=latestarticles
6. https://www.sciencedirect.com/science/article/abs/pii/S0925492715000037
7. https://www.sciencedirect.com/science/article/abs/pii/S0006322312005847
8. https://www.cambridge.org/core/journals/cns-spectrums/article/abs/posttraumatic-stress-disorder-symptom-severity-is-associated-with-left-hippocampal-volume-reduction-a-metaanalytic-study/284BD982CC1E2F945EB71C31C9794375
9. https://www.sciencedirect.com/science/article/abs/pii/S000632231731990X
10. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker#:~:text=(BY%2Doh%2DMAR%2D,molecular%20marker%20and%20signature%20molecule.
11. https://www.lsi.umich.edu/news/2022-10/why-scientist-thinks-rna-much-more-fun-dna#:~:text=I%20actually%20think%20that%20for,treating%20cancers%20and%20infectious%20disease.
12. https://en.wikipedia.org/wiki/DNA
13. https://en.wikipedia.org/wiki/RNA
14. https://www.sciencedirect.com/science/article/abs/pii/S0165993619301803
15. Anastasiya Klimenko, Vasyl Nagibin, Anastasiia Horlova, Yulia Dobropolska, Ruslan Bogovik, Dmytro Stroy, Dmytro Isaev & Victor Dosenko (2024). Downregulation of lncRNAs Gomafu, NONMMUT033604.2, and NONMMUT064397.2 in the hippocampus of mice with model of post-traumatic stress disorder, The World Journal of Biological Psychiatry, 25:5, 283-290, DOI: 10.1080/15622975.2024.2342849