Predicting treatment success in anxiety disorder patients by use of biomarkers

Symptoms of anxiety are based on amygdala responsiveness, which can be evoked
by the activation of multiple different brain circuits. We aim to characterize
the following neural mechanisms that might cause amygdala hyper­responsiveness*
high locus coeruleus drive, low prefrontal control or increased amygdala
sensitivity. We hypothesize that variation in local sensitivity and variation
in specific control mechanisms may explain why certain individuals are more
fearful than others. The same phenotype may
result from different neural mechanisms.
State-of-the-art treatment for anxiety disorders is cognitive behavioral
therapy, in particular exposure therapy. As we know that cognitive therapy
improves prefrontal control processes, we assume that patients with a low
prefrontal control have the highest benefit from cognitive therapy compared to
patients with other non-prefrontal mechanisms.
The aim of this study is to identify which biomarkers predict the outcome of
cognitive behavioral therapy. If we can define a reliable biomarker, it would
be possible to select the most beneficial therapy for a patient based on his or
her individual biomarker leading to symptoms of anxiety. Predictive biomarkers
would help to individualize treatment and shorten treatment time and costs.

We select patients that have a diagnosed anxiety disorder and are already
enrolled to start an intensive exposure therapy program at Pro
Persona/Overwaal. In an fMRI session their individual underlying neural
mechanism (biomarker) associated with their symptoms of anxiety will be
determined. After completion of the therapy program an evaluation questionnaire
battery is in place at Pro Persona. We will analyze the data of the evaluation
in regard to potential predictive power of previously established biomarkers in
a patient. Our aim is to identify biomarkers that reliably predict the
treatment success of cognitive behavioral therapy for the individual patient.

Patients will be informed about the study by their therapist. Two weeks before
starting the intensive therapy program, a preparation meeting is routinely
scheduled for all patients. During this appointment, the therapist will inform
the patient about the rational of the study and hand out information material.
Patients will be asked if they agree to share their contact data with the
researcher to be contacted in case they decide to participate. The researcher
contacts the patient 2 days after they received the information material to
schedule an appointment for an exposure session and the MRI session at the
Donders institute.
First, an exposure session will be conducted by a psychologist to familiarize
the patient with the scanner set-up and to decrease potential anxiety of lying
in the scanner. After a successful exposure session patients take part in the
fMRI session. At the institute, participants will be fully informed about the
rationale and procedure of the fMRI investigation and will be asked to give
their consent. During the fMRI investigation, three tasks will be applied to
classify the dominant neuronal mechanism in the individual patient. A pre­
frontal regulation task will be applied to monitor activity in the prefrontal
cortex. Amygdala reactivity will be monitored by applying an emotional face
processing task. Salience processing will be used to monitor activity in the
locus coeruleus. Stimulus materials for visual stimulation are taken from
standardized stimulus sets. Tactile stimulation is applied using stimulation by
electrodermal stimulation.
After the fMRI session, participants are asked to complete a set op
questionnaires evaluating anxiety, depression, personality traits and emotion
regulation strategies.
Therapy outcome is evaluated at pro Persona right after the treatment - this
evaluation is conducted for all patients, regardless if they particpated in the
study or not. Participants of the study fill in the same set of questionnaires
again three months after completing their treatment in order to measure
long-term benefit of exposure therapy.

MRI is a non-­inversive imaging technique. Only occasionally (< 0,5%) subjects
report vertigo­-like sensations and/ or slight nausea symptoms due to movement
in the static field of the scanner. Sensitivity to these effects varies
considerably between individuals. In rare cases, minimal muscle contractions
due to nerve stimulation abating when the scanning procedure stops. Acoustic
noise from the MRI scanner can be reduced wearing shielded earphones during the
scanning procedures.
Burdens and risks are very minimal to negligible. Since we are dealing with a
highly anxious population, an MRI measurement might create more stress than in
a healthy population. Therefore, an exposure session in the dummy scanner will
be scheduled before the actual MRI session, to familiarize patients with the
MRI environment and to decrease potential fears.

Incidental neurological findings during the fMRI session are reported to the
participant's GP.