"Precision medicine" leverages technology and mathematical tools to individualize care. Precision-medicine approaches are on the cutting edge of medicine, and as such are not always ready for primetime. They are often the subject of controversy. Some clinicians and patients are eager to try new things right away, while others prefer to wait to see if they work and if they cause unexpected adverse reactions, also known as "side effects."
A new paper, "Identifying PTSD symptoms typologies: A latent class analysis" (Campell, Trachik, Goldberg and Simpson, 2020), discussed further below, highlights the precision medicine trend with findings on the nature of post-traumatic stress disorder.
Design My Care
Precision medicine includes developments such as pharmacogenomics to assist in selecting medications most likely to work well without side effects, and neuroimaging to guide treatment choice, for example, in determining whether psychotherapy or medications would be most likely to succeed for a given patient.
Recent research shows posttraumatic epigenetic changes are reversed by therapy. Functional neuroimaging shows successful therapy normalizes neural network activity in the brain as it reduces symptoms.
Machine learning tools have been used to identify different biologically-based subtypes of depression (“biotypes”). Researchers can scan the brains of suicidal patients using AI, which attempts to learn who is more likely to harm themselves. These are only a few examples of how emerging tools can take our understanding of mental illness to a new level and begin to inform treatment.
What is PTSD?
Current psychiatric diagnosis is based on clinical experience, history, expert consensus, and analysis of existing research. In medicine, illnesses are diagnosed by meeting criteria. For PTSD, the presence of a traumatic event is always required, as is a duration of at least one month, clinically significant distress or dysfunction, and the absence of another cause for the symptoms (such as a medical condition that mimics psychiatric illness).
Like a prix fixe menu where you can choose items from several courses, the DSM-5 PTSD diagnosis requires 1) at least one intrusion symptom, 2) at least one avoidance symptom, 3) at least two negative alterations in mood and cognitive symptoms, and 4) at least two marked alterations in arousal or activity symptoms. There are 636,120 combinations that add up to PTSD. There is also a dissociative subtype, where symptoms of derealization or depersonalization are present. This subtype stands alongside those noted below.
The current system is accurate with room for improvement, and it has evolved since 1980, when PTSD was first made an official diagnosis. Debate continues, including disagreement about adding Complex PTSD (cPTSD) as an official diagnosis. cPTSD was recently included by the World Health Organization in the ICD-11 system.
Deep Dive into Trauma
The current study used “latent class analysis” with the National Epidemiological Survey on Alcohol and Related Conditions (NESARC III). This survey collected data from a representative sample to reflect the general U.S. population. Of the over 36,000 participants, almost 2,400 met criteria for PTSD at some point in their lives.
Participants in this survey completed a variety of measures looking at PTSD, depression, anxiety, eating and personality disorder diagnoses; substance use disorders; suicide attempts; recent social stressors (“social instability”) including homelessness, unemployment, lack of health insurance, and need for public assistance; sociodemographic data on ethnicity, income, education, gender, and related factors; and overall mental and physical health to assess quality of life.
Researchers found that a four-factor model allowed for the best data fit. The four subtypes of PTSD were:
1. Dysphoric (23.8 percent): Intrusive thoughts; avoidance of situations and thoughts related to the trauma; negative thoughts and feelings; isolation, numbing and irritability; and difficulty with sleep and concentration.
They were more likely to be younger, and male. They were less likely to have experienced combat. They were less likely to receive medication for PTSD. They were more likely to be diagnosed with depression, and less likely to be diagnosed with anxiety. They were more likely to use nicotine.
2. Threat (26.1 percent): Increased re-experiencing symptoms; high self-blame and negative emotion; lower levels of loss of interest, numbing, isolation and irritability; and high levels of physiologic arousal (“hyperarousal”). They were more likely to be older, and less likely to have recent homelessness or unemployment.
They were more likely to have personally experienced natural disasters, and had illnesses or injury to people close to them. They were less likely to report childhood sexual abuse as their worst trauma, and reported better mental health. They tended to have fewer additional psychiatric diagnoses.
3. High Symptom (33.7 percent): Elevated levels of all symptoms except trauma-related amnesia and high-risk behaviors. They were more likely to be female, less likely to be White, reported lower education and income levels, and were more likely to have recent public assistance, homelessness, and unemployment. They were more likely to report combat and childhood sexual abuse as their worst trauma, were younger when they developed PTSD and had it longer, and reported worse mental and physical health.
They were more likely to have received therapy and/or medication treatment for PTSD. They had higher rates of other psychiatric conditions, including anxiety disorders, bipolar disorder, chronic depression, marijuana and alcohol use disorders, and personality disorders including Borderline, Schizotypal and Antisocial. This group most closely resembles cPTSD.
4. Low Symptom (16.3 percent): Lower levels of all symptoms, except for intrusive thoughts, negative emotions, and hypervigilance. People in this group were more likely to have higher income levels. They were more likely to report the worst trauma to someone close to them, rather than to themselves personally, and were less likely to report personal war trauma.
They tended to be older and have PTSD for a shorter time, and to have better mental and physical health. They were less likely to have received treatment with therapy and/or medications. They were less likely to have other psychiatric diagnoses, and less likely to have personality disorders.
While requiring replication and elaboration, this research moves the needle for precision medicine by providing a useful framework for identifying different presentations of PTSD. It could allow for a more refined approach to prevention and treatment, both for individual patients and clinicians. It is worth noting that while some categories had relatively low symptoms (e.g., lower risky behavior in the High Symptom type compared to the others), this does not mean that those symptoms are at a normal level).
Having a better sense of what we are dealing with on a foundational level is an important step. This work highlights the importance of the social determinants of illness. While PTSD is an individual diagnosis, for High Symptom especially, it is clear that socioeconomic and related conditions are relevant factors for millions of people, and for other subtypes, social determinants seem to be protective. PTSD is not only a psychiatric diagnosis; it reflects deep societal issues and plays out over generations.
According to study authors Drs. Trachik and Campbell,
"Our research team is particularly interested in the precision medicine element of this work. For future research we are most interested in a treatment matching dataset to see if these typologies are associated with treatment outcome, dropout, or treatment adherence. It is our hope that given the debate in the literature about the appropriate diagnostic definition of PTSD, that the typologies work adds to discussions about potential treatment considerations for those with PTSD."
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