Brain imaging in Posttraumatic Stress Disorder (PTSD): effects of paroxetine and Trauma-Focused Cognitive Behavioural Therapy (TF-CBT)

In patients with post traumatic stress disorder (PTSD) several structural as
well as functional brain abnormalities and dysfunctions have been found, such
as in the temporal structures (i.e,. the limbic system including amygdala and
hippocampus) and the prefrontal cortical brain regions. Regarding structural
changes in the brain of PTSD patients, the most salient finding is that
hippocampal volumes are smaller in patients with PTSD. Concerning alterations
in brain activation, as measured with functional neuroimaging, it has been
found that trauma-related memories in PTSD cause hyperactivation of the
temporal brain regions like the amygdale and insula. In addition, data suggests
a reciprocal relation between the function of the medial prefrontal cortex and
amygdalae function in PTSD and that responses to fear and stress in PTSD
patients are not sufficiently suppressed by the medial prefrontal cortex. It
is, however, unclear whether these disturbances are pre-existent risk factors
or occurring after trauma and/or alongside PTSD. Moreover, there is yet little
evidence for the influence of effective treatment on functional differences.
The proposed study is part of our main study *The effectiveness of Paroxetine
versus Trauma-Focused Cognitive Behavioural Therapy in the treatment of
Posttraumatic Stress Disorder (PTSS)* (MEC 09/080 # 09.17.0843as).

Our main objective is to assess whether structural and functional differences
in the brain can be demonstrated between PTSD patients and controls during
performance of an emotionally evoked task, in resting state and during a
working memory task. Secondly, we aim to assess whether any structural and
functional differences will be apparent following effective treatment and
whether functional differences will be found between two different treatments,
i.e., trauma-focused cognitive behavioural therapy (TF-CBT) and the Selective
Serotonine Reuptake Inhibitor (SSRI) paroxetine. Furthermore, the association
of neuro-immune, neuro-endocrine and neurocognitive data with structural and
functional data will be explored as well as white matter integrity.

We propose to conduct an fMRI study comparing patients with chronic PTSD (N=48)
[taking part in the main study randomized to pharmacological treatment with
paroxetine (N=20) or to psychotherapy (TF-CBT) (N=20) or taking part in a pilot
study of breathing biofeedback as an adjunct to TF-CBT (N=8)] with trauma
exposed controls (N=20) and healthy controls (N=20). All participants will be
examined using (functional) Magnetic Resonance Imaging ((f)MRI). PTSD patients
(N = 48) will be scanned prior to treatment, immediately after treatment and
12 months later and data from assessments already performed in the main study
and biofeedback pilot study, respectively, will be linked to the current fMRI
substudy. Controls (N=40) will have a single scanning moment and additional
neuropsychological, neuro-immune and neuro-endocriene data will be collected
only once for these controls.
Patients suffering from chronic PTSD who are randomly assigned to either 8-12
weekly sessions of TF-CBT (N = 20) or 24-weeks of flexible-dose open treatment
(20 mg to a maximum of 60 mg) with paroxetine (N = 20) or to TF-CBT with an
adjunct of biofeedback training (N=8) will be scanned prior to treatment and 1
week after treatment. PTSD-patients (N=40) taking part in the main treatment
study will also be assessed on the long term, i.e., 12 months after respective
treatments are finished. Measurements will include (f)MRI and DTI. The control
groups will be assessed at one single time-point. All participants will perform
two tasks, one emotionally evoked task and one working memory task. In
addition, participants will be scanned during resting state.

The burden and risks associated with participation in this study is reasonable.
The participants who are receiving either trauma focused behavioural therapy
(TF-CBT) or treatment with paroxetine, both considered to be the effective
treatments for PTSD, will for this study be exposed to the (f)MRI before and
immediately after treatment. This may be considered a burden, but no risks in
terms of adverse events or treatment outcome are related with this procedure.
Participants will receive an additional compensation for participating in the
study.