Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross‐validation machine learning approach

Abstract

ObjectivesEmbedded in the Collaborative Research Center “Fear, Anxiety, Anxiety Disorders” (CRC‐TRR58), this bicentric clinical study aims at identifying biobehavioral markers of treatment (non‐)response by applying machine learning methodology with an external cross‐validation protocol. We hypothesize that a priori prediction of treatment (non‐)response is possible in a second, independent sample based on multimodal markers.MethodsOne‐session virtual reality exposure treatment (VRET) with patients with spider phobia was conducted on two sites. Clinical, neuroimaging, and genetic data were assessed at baseline, post‐treatment and after 6 months. The primary and secondary outcomes defining treatment response are as follows: 30% reduction regarding the individual score in the Spider Phobia Questionnaire and 50% reduction regarding the individual distance in the behavioral avoidance test.ResultsN = 204 patients have been included (n = 100 in Würzburg, n = 104 in Münster). Sample characteristics for both sites are comparable.DiscussionThis study will offer cross‐validated theranostic markers for predicting the individual success of exposure‐based therapy. Findings will support clinical decision‐making on personalized therapy, bridge the gap between basic and clinical research, and bring stratified therapy into reach. The study is registered at ClinicalTrials.gov (ID: NCT03208400).

Behavioral and Magnetoencephalographic Correlates of Fear Generalization Are Associated with Responses to Later Virtual Reality Exposure Therapy in Spider Phobia

“…SPQ-reductions from pre-to post-treatment assessment (t(88)=20.59, p<.001, d=2.18, M Pre = 22.61, SD Pre = 2.00; M Post = 15.54, SD Post = 3.02) supported the expectation of a highly effective VRET (for clininical effects, see also [36] and SM2.1). According to our primary outcome criterion (30% SPQ-reduction [28]), 48.31% of all patients responded to VRET (SPQ-reductions of 42.06% in responders and 20.66% in non-responders). SPQ-responders were also characterized by stronger percentual pre-to-post reductions of avoidance in the BAT than non-responders (t(87)=2.140, p=.035).…”

“…Responders were characterized by SPQ-reductions of >30%, i.e. a clinically meaningful response (see [28]).…”

“…Patients first underwent a clinical pre-treatment assessment, which included primary and secondary outcome measures, demographic and psychometric questionaires, followed by the behavioral and MEG assessment on fear generalization (+13.03 days, SD=9.38), the VRET (+27.46 days, SD=10.35), and the clinical post-treatment assessment (+M=32.70, SD=12.02, see Figure 1, for details see [28] and SM1.2-1.2.2). During VRET, patients were exposed to virtual spiders in up to five different scenarios.…”

Neural processing of emotional facial stimuli in specific phobia: An fMRI study

“…The SP group was part of a subproject of a Transregional Collaborative Research Center (CRC‐TRR58 “Fear, Anxiety, Anxiety Disorders”). Complete information on the methods and goals of this project can be found elsewhere (Schwarzmeier et al, 2019). The control group was acquired in parallel within the Marburg‐Münster Affective Disorders Cohort Study (MACS; Kircher et al, 2019; Vogelbacher et al, 2018) using the identical magnetic resonance imaging (MRI) setup.…”

“…N = 11 participants dropped out between measurement points. For full inclusion criteria, see Schwarzmeier et al (2019). From the initial sample, n = 111 participants fulfilled these criteria.…”