טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentMeir Tamar
SubjectCytokine Patterns, TLR Polymorphisms and the Risk for Post
Traumatic Stress Disorder (PTSD) in Severely
Wounded Vehicle Accident Casualties
DepartmentDepartment of Medicine
Supervisors Professor Shimon Pollack
Professor Emeritus Ehud Klein
Full Thesis textFull thesis text - English Version


Abstract

Vehicle, work or home accidents often constitute a traumatic event to the individual, with serious short- and long-term psychological consequences. Some survivors of severe vehicle accidents suffer early after the incident from acute stress disorder (ASD) which progresses to PTSD in 40% of these cases. Skeletal and tissue injuries may stimulate, through toll like receptors (TLRs), increased pro-inflammatory cytokine secretion that can act upon the central nervous system and initiate or accelerate affective disorders such as depression. Because ASD and its progression to PTSD have not, as of yet, been studied in this context, the aim of this study was to evaluate several psycho-immune parameters in severely wounded vehicle accident victims and associate them with ASD and its progression to PTSD. Forty eight patients with operable big bone injuries, aged 20-60, were matched with healthy controls. On the 3rd or 4th day of hospitalization patients were interviewed and psychologically evaluated. Samples of 30 ml heparinized venous blood were drawn and proportions of mononuclear cell sub-populations, in vivo and mitogen (LPS or PHA)- stimulated  in vitro cytokine levels and TLR4 & TLR9 polymorphisms were evaluated. One month later, patients were psychologically evaluated for PTSD Symptoms. The results showed that ASD positive patients generally had low in-vivo cytokine levels, and that the lowest in-vivo and highest in-vitro cytokine levels were observed in the patients who eventually developed PTSD. Among the various tested cytokines, in- vivo IL-8 levels were positively associated with ASD scores whereas in- vivo TGF-β levels were negatively associated with PTSD scores. Depression and emotion focused coping were significantly correlated with serum IL-8 levels, and anxiety was significantly correlated with serum TGF-β levels. Regarding TLR polymorphism, a higher prevalence of heterozygous TLR9 SNP 2848 was found in both ASD positive and PTSD positive patients. Overall, our results show trends of characteristic cytokine patterns and TLR9 polymorphism in trauma patients whose ASD developed into PTSD. These findings can serve as a marker for predicting the development of PTSD in patients with severe trauma, and thus enable early psychological intervention.