Consequences of rape : injuries, posttraumatic stress and neuroendocrinological changes

Each year, approximately 3-4% of the Swedish female population experiences a sexual assault. Only a small percentage of these women will report the assault to the police, and even fewer will seek medical help. This thesis is based on studies on women seeking medical help at the Emergency Clinic for Raped Women at Stockholm South General Hospital, in Stockholm, Sweden, after having been sexually assaulted. The aim of the thesis was to improve the knowledge about women seeking medical help after rape, explore risk the factors for the development of PTSD, and explore the neuroendocrinological changes in PTSD patients. Study I compared intimate partner assaults to assaults by other known assailants and to assaults by strangers in terms of the use of physical violence and risk of sustaining injuries. A retrospective review of patient files and forensic examinations from the acute visits of 690 consecutive women showed that women who were sexually assaulted by their intimate partners more frequently reported physical violence (OR 4.1) than women assaulted by strangers (OR = 2.0) and acquaintances (OR = 1.0). Extragenital injuries showed a trend towards being more frequently seen after intimate partner assaults as compared to the two other groups. Genital injury prevalence was not related to the victim-assailant relationship. Study II aimed to explore the prevalence of PTSD six months after sexual assault and explore the potential risk factors for the development of PTSD. Two hundred and one women were assessed at baseline regarding mental health using self-rating questionnaires and followed up after six months with questionnaires, as well as a clinical interview for PTSD diagnosis. Thirty-nine percent of the women had developed PTSD at the six-month assessment, and 47% suffered from moderate or severe depression. The major risk factors for PTSD were having been assaulted by multiple assailants, suffering from acute stress disorder shortly after the assault, having been exposed to several acts during the assault, having been injured, having co-morbid depression, and having a history of two or more earlier traumas. Study III was conducted in order to adjust the concentrations of various endogenous steroids in Study IV for possible diurnal variation. Blood samples were taken every 4 th hour during a 24-hour period in 10 premenopausal women in the follicular phase of the menstrual cycle and assessed regarding their concentrations of allopregnanolone, cortisol, cortisone, 11deoxycortisol, progesterone, 17OH-progesterone, pregnenolone, 17OH-pregnenolone, DHEA, androstenedione, testosterone, estrone, and estradiol. The results suggested that all steroids, apart from the estrogens, had a diurnal variation in the follicular phase. All steroids, apart from allopregnanolone, had a diurnal curve similar to that of cortisol (i.e., with a peak in the morning just after awakening and the lowest concentrations during the night). Allopregnanolone had a less steep curve, with high concentrations throughout the day and a peak around noon. Study IV assessed whether concentrations of the same endogenous steroids measured in Study III in the immediate aftermath of rape could predict the development of PTSD and depression. The study design was the same as in Study II but with a blood sample added at the acute visit. Low concentrations of cortisol and the ∆5 steroids (pregnenolone, 17OHpregnenolone, and DHEA) shortly after rape were associated with a history of earlier traumatization, and low allopregnanolone concentrations shortly after rape were associated with a psychiatric treatment history. However, there was no association between any of the steroids and pre-existing PTSD or the development of PTSD after six months. Results also suggested an association between menstrual cycle phase and the HPA axis. Study V assessed the sensitivity of the GABA-A receptor in 10 drug naive patients with PTSD as compared to 10 healthy controls measured with saccadic eye velocity (SEV) and subjective ratings of sedation. SEV was measured after injections of the positive GABA-A receptor modulator allopregnanolone, the GABA-A receptor agonist diazepam and the GABA-A receptor antagonist flumazenil, each on separate occasions, and during the follicular phase of the menstrual cycle. The results showed that the PTSD patients were less sensitive to GABA-A-receptor-active substances, probably due to an acquired chronic tolerance to these substances caused by chronic exposure of neuroactive steroids over a long period of time. Conclusions: Sexual assaults by intimate partners are more violent and result in injuries just as often as assaults by strangers. However, physical injuries after sexual assaults are generally few and genital injuries minor. PTSD and depression, on the other hand, are common after sexual assaults, and an increased risk of developing PTSD is caused by a combination of victim vulnerability and the extent and nature of the current assault. Concentrations of endogenous steroids in the immediate aftermath of sexual assault (after having been adjusted for their diurnal variation) cannot predict the development of PTSD. However, low concentrations of several steroids are seen in previously traumatized women and in women with a psychiatric morbidity, two factors that have both been shown to increase the risk of developing PTSD. Finally, as a consequence of the reduced sensitivity of the GABA-A receptor in PTSD patients, the use of GABA-A-receptor-active compounds, such as sleeping pills, will be less useful for this group of patients. LIST OF PUBLICATIONS I. Moller AS, Backstrom T, Sondergaard HP, Helstrom L. Patterns of injury and reported violence depending on relationship to assailant in female Swedish sexual assault victims. J Interpers Violence 2012 Nov;27(16)3131-3148. II. Tiihonen Moller A, Backstrom T, Sondergaard HP, Helstrom L. Identifying risk factors for PTSD in women seeking medical help after rape. PLoS One 2014 Oct 23;9(10) III. Tiihonen Moller A, Backstrom T, Sondergaard HP, Kushnir MM, Bergquist J, Helstrom L. Diurnal variations of endogenous steroids in follicular phase of the menstrual cycle. Manuscript IV. Tiihonen Moller A, Backstrom T, Sondergaard HP, Kushnir MM, Bergquist J, Helstrom L. Endogenous steroids in the immediate aftermath of rape as predictors for the development of PTSD and depression. Manuscript V. Tiihonen Moller A, Backstrom T, Nyberg S, Sondergaard HP, Helstrom L. Women with PTSD have changed sensitivity to GABA-A receptor active substances. Psychopharmacology (Berl). 2014 Oct 28 CONTENTS