The biological stress-system in sexually assaulted female adolescents with PTSD and its response to cognitive behavior therapy

Sexual assault, including rape, is a gender-specific crime that
disproportionally affects female adolescents. Half of adult female victims of
sexual assault suffer from Post Traumatic Stress Disorder (PTSD) after three
months and 30-45% still do so after 1 year. Prospective data in PTSD in female
adolescents have not been studied. The biological correlates of sexual assault
have received little attention in research. Since sexual assault is a highly
stressful experience, it is hypothesized that there is an association with the
functioning of the body*s stress systems, such as the Hypothalamic Pituitary
Adrenal (HPA)-axis and the (nor)adrenergic system. Three products of these
systems will be addressed in girls who have been sexually assaulted and
compared with non-traumatized controls: salivary cortisol, DHEA(S), and
salivary alpha amylase (sAA).
If PTSD is associated with dysregulated neuroendocrine measures, these measures
would hypothetical *renormalize* if the PTSD is treated successfully in
cognitive behavioral therapy (CBT). In this study, the association between PTSD
reduction and changes in neuroendocrine variables will be measured.
Studying the relation between clinical and biological changes in sexually
assaulted adolescents after CBT can provide more insight into the causal
mechanism of the HPA-axis dysregulations found in victims of sexual assault.
Also, results from this study can identify the potential to changeability of
these dysregulations after CBT and may enlarge pharmacological treatment
possibilities of PTSD. Finally, results of this study may help to discriminate
PTSD patients who are less responsive to CBT and, hence, may require other
interventions.

Major objectives:

1. To measure basal salivary cortisol and DHEA(S) levels and salivary cortisol
responses to low-dose dexamethasone in sexually assaulted adolescents with PTSD
compared to cortisol and DHEA(S) values in non-traumatized controls.

2. To measure the association between PTSD reduction and changes in cortisol
and DHEA(S) levels of sexually assaulted adolescents with PTSD in response to
trauma-focused CBT.

3. To determine the predictive value of salivary cortisol and DHEA(S) in PTSD
patients at baseline for successful CBT

4. The measure the correlation between self-rated subjective distress in PTSD
patients in response to the trauma narrative and the amplitude of the cortisol
response and sAA response.

5. To determine the predictive value of the amplitude of the cortisol response
and sAA response to the trauma narrative for successful CBT.

A cross-sectional study will be carried out in 100 sexually assaulted
adolescents with PTSD and in 100 age- and gender-matched non-traumatized
control subjects (recruited from secondary schools in the Utrecht area).
History of sexual trauma in the control group will be assessed with checklist
questionnaires. The patient and control group will be compared on salivary
cortisol and DHEA(S) output after awakening and at 5 pm and with respect to a
dexamethasone suppression test (DST).

A prospective study will be carried out in 50 sexually assaulted adolescents
with PTSD (subgroup of the above mentioned 100 patients) who will receive
Cognitive Behavior Therapy (CBT) according to STEPS, individual or in group. At
post-treatment (T2), at 6 month follow-up (T3) and at 12 months follow-up (T4),
adolescents and parents will be re-assessed according to the standardized
psychological assessment procedure. Also, salivary cortisol and DHEA(S) output
after awakening, at 5 pm and cortisol response to DST will be determined again
at T2, T3 and T4. The association between PTSD reduction and changes in
neuroendcorine variables will be measured.

In 30 patients with PTSD (subgroup of the above mentioned 50 patients who will
be provided STEPS) who followed the STEPS group treatment, saliva will be
collected in every patient during the session of trauma narrative exposure.
Salivary alpha amylase (sAA) will be assessed in this saliva and related to
treatment outcome.

At the Psychotrauma Center for Children and Youth in Utrecht (UMC Utrecht), a
CBT protocol has been developed for sexually assaulted adolescents with PTSD
and their parents, named STEPS. Details of the STEPS protocolized treatment are
being published (Bicanic & Kremers, 2007). STEPS incorporates several
intervention techniques also used in the effective cognitive behavior treatment
protocols, such as psycho-education, writing assignments, trauma narrative,
exposure in vivo and cognitive restructuring. STEPS can be administered
individually or in a group. The group treatment consists of eight weekly
sessions of two hours each and includes a parallel parents* group. STEPS
targets at reducing PTSD symptomatology.
A recent pre-post pilot study in the Trauma Center in Utrecht showed a clinical
and statistical significant improvement after group STEPS in 34 raped
adolescent girls at post-treatment and at 6- and 12-month follow-up with
respect to reduced levels of PTSD, anxiety and depression.

In the Netherlands, 1 in 6 girls between the age of 12-25 have experienced
forced sex (De Graaf et al, 2005). A part of this group seriously suffers from
this trauma and is impeded in development. It is essential to gain more
knowledge on the process of (biological and psychological) recovery after
sexual assault. In order to gain knowledge on functioning of the stress-system
in assaulted and raped girls with regard to the effects of psychotherapy, it is
inevitable to collect saliva by salivettes at different moments before and
after therapy. Collecting saliva is a non-invasive and easy method, that can be
performed at home. We expect no physical risk from sampling saliva and from
taking dexamethasone. A low dose < 1,0 mg dexamethason should be enough to show
suppression (Ebrecht, 2000). When a low dose dexamethason is taken orally, no
serious side-effects are expected. In clinical practice it is common to start
with 0.75 - 15 mg dose daily and this dose is used for a longer period of time.
Possibly, girls who have been raped orally (5-10% of all referrals) might
experience problems with taking the salivette in their mouth. In case of oral
rape, the patient will be asked if participation is doable.
De burden of the research is saliva collection and the dexamethason suppression
test for all patiënten with PTSD as a result of sexual assault. For a subgroup
who received STEPS treatment, saliva collection and dexamethason suppression
test will be repeated directly after treatment and at 6-month and 12-month
follow-up. From this subgroup, saliva will be collected in those who receveid
group treatment coording to STEPS, durong the trauma narrative exposure
session.
The researchers believe that performing the reserach is justified, after taking
into account the burden and risk.