Abstract
ObjectivesPosttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables.MethodsAssociation of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables.ResultsThe categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD.ConclusionsThe present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.
Highlights
Posttraumatic stress disorder (PTSD) is obligatorily associated with the exposure to one or more extreme traumatic actual or threatened events, such as death, serious injury or sexual violation and integrated in the chapter of “Trauma- and Stress-Related Disorders” in the current Diagnostic and Statistical Manual DSM-5 (American Psychiatric Association 2013)
To characterize the role of genetic risk and other putative PTSD moderating variables such as traumatic life events, coping style, age at war and sex, we examined their association with the categorical phenotype of PTSD in 189 patients suffering from current PTSD, 132 probands with remitted PTSD and combined in comparison to 337 healthy volunteers (Table 2)
The present analysis in the South Eastern Europe (SEE)-PTSD cohort confirms the assumption of genetic components associated with PTSD by showing significant predicted polygenic risk for PTSD as diagnosis in the remitted and total sample, while no such effects have been found for symptom severity measures
Summary
Posttraumatic stress disorder (PTSD) is obligatorily associated with the exposure to one or more extreme traumatic actual or threatened events, such as death, serious injury or sexual violation and integrated in the chapter of “Trauma- and Stress-Related Disorders” in the current Diagnostic and Statistical Manual DSM-5 (American Psychiatric Association 2013). The core characteristics of PTSD are re-experiencing the traumatic event by intrusions and flash-backs, avoidance on cognitive, social and behavioral levels, negative changes in thoughts, hypervigilance, anxiety and other affective disturbances. PTSD prevalence reaches up to 30% in war-affected communities or refugees (Priebe et al 2010; Blackmore et al 2020). The course of PTSD varies with chronic persistence of symptoms in 50% of affected subjects leading to tremendous individual burden and high socioeconomic costs (Morina et al 2014). PTSD is often comorbid with other psychiatric disorders, such as depression and substance abuse (Jacobi et al 2014; Morina et al 2018)
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