Virtual Reality Exposure in Spider Phobia

Exposure Treatment in Anxiety Disorders: Proof of Principle for an a Priori Response Prediction Approach

While knowledge on the neurobiological signatures of fear and anxiety disorders and, in particular, their association with treatment outcome is accumulating, clinical translation still awaits empirical proof of evidence. Exposure-based cognitive-behavioral therapy (CBT) is a first-line treatment, but clinically significant change is only seen in approx. 50-65% of patients. Patient stratification is a powerful option to increase treatment response; however, developing prognostic markers suitable for single-patient predictions still is in its infancy and crucially requires external cross-validation embedded within an a priori prediction approach - a procedure yet largely missing in the field of biomarker research. Employing a bicentric strategy the aim of this study is to test the hypothesis that a priori prediction of treatment outcome based on neurobiological measures is possible in a second, independent sample. Building upon findings from previous mechanistic studies, These will be incorporated into the development of a predictive pattern comprising fear-relevant genotypes and molecules targeting neuropeptides, related epigenetic signatures as well as neurofunctional activation patterns associated with fear circuitry functions, and clinical data. Pre-treatment neurobiological signatures will be tested for their potential as a predictive response marker towards behavioral exposure (virtual reality exposure treatment (VRET) and an in vivo behavioral avoidance test) in a model disorder of fear circuitry dysfunctions (spider phobia). Multivariate pattern analyses employing a machine learning framework will be used to generate predictions on the individual patient level and to cross-validate markers in a second, independent sample. While at site A predictions will be generated following completion of the treatment, response will be predicted at site B a priori, but in a double-blind manner. Comparison of observed vs. predicted response rates will serve as a test of hypothesis. In addition, neuroplastic (on a subsample) and epigenetic changes induced by VRET treatment will be assessed following treatment and, in case of epigenetics, also after 6-months follow-up.

Change (in cm) in the extend to which a living spider can be approached from before vs. after 6 month follow-up period

Inclusion Criteria: 18 or older specific phobia (animal subtype: spider phobia) according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Version (DSM-5) right-handedness Caucasian descent willingness to participate in massed exposure Exclusion Criteria: patients exhibiting a primary other anxiety disorder (panic disorder, agoraphobia, social phobia, generalized anxiety disorder), acute suicidality, psychotic, bipolar I, obsessive-compulsive disorder, posttraumatic stress disorder, severe major depression, borderline personality disorder or substance dependency (except nicotine) patients fulfilling MRI-related exclusion criteria patients with current pharmacological or psychotherapeutic treatment, as well as those already previously treated with exposure-based CBT pregnancy or lactation

Center of Mental Health, Dept. of Psychiatry, Psychosomatics, and Psychiatry, University Hospital of Wuerzburg

Schwarzmeier H, Leehr EJ, Bohnlein J, Seeger FR, Roesmann K, Gathmann B, Herrmann MJ, Siminski N, Junghofer M, Straube T, Grotegerd D, Dannlowski U. Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross-validation machine learning approach. Int J Methods Psychiatr Res. 2020 Jun;29(2):e1812. doi: 10.1002/mpr.1812. Epub 2019 Dec 8.