Dataset Information

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

ABSTRACT: OBJECTIVES:Embedded 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. METHODS:One-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. RESULTS:N = 204 patients have been included (n = 100 in Würzburg, n = 104 in Münster). Sample characteristics for both sites are comparable. DISCUSSION:This 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).

SUBMITTER: Schwarzmeier H

PROVIDER: S-EPMC7301283 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Schwarzmeier Hanna H Leehr Elisabeth Johanna EJ Böhnlein Joscha J Seeger Fabian Reinhard FR Roesmann Kati K Gathmann Bettina B Herrmann Martin J MJ Siminski Niklas N Junghöfer Markus M Straube Thomas T Grotegerd Dominik D Dannlowski Udo U

International journal of methods in psychiatric research 20191208 2

<h4>Objectives</h4>Embedded 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.<h4>Methods</h4>One-session virtual reality exposure treatment ...[more]

PMID: 31814209

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Project description:Glucocorticoids reduce phobic fear in patients with anxiety disorders. Previous studies have shown that fear-related activation of the amygdala can be mediated through the visual cortical pathway, which includes the fusiform gyrus, or through other pathways. However, it is not clear which of the pathways that activate the amygdala is responsible for the pathophysiology of a specific phobia and how glucocorticoid treatment alleviates fear processing in these neural networks. We recorded the brain activity with functional magnetic resonance imaging in patients with spider phobia, who received either 20 mg of cortisol or a placebo while viewing pictures of spiders. We also tested healthy participants who did not receive any medication during the same task. We performed dynamic causal modelling (DCM), a connectivity analysis, to examine the effects of cortisol on the networks involved in processing fear and to examine if there was an association between these networks and the symptoms of the phobia. Cortisol administration suppressed the phobic stimuli-related amygdala activity to levels comparable to the healthy participants and reduced subjective phobic fear. The DCM analysis revealed that cortisol administration suppressed the aberrant inputs into the amygdala that did not originate from the visual cortical pathway, but rather from a fast subcortical pathway mediated by the pulvinar nucleus, and suppressed the interactions between the amygdala and fusiform gyrus. This network changes were distinguishable from healthy participants and considered the residual changes under cortisol administration. We also found that the strengths of the aberrant inputs into the amygdala were positively correlated with the severity of spider phobia. This study demonstrates that patients with spider phobia show an aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli and that cortisol administration can alleviate this fear-specific neural connectivity.

Project description:ObjectivesUsing a nationally-representative, cross-sectional cohort, we examined nutritional markers of undiagnosed type 2 diabetes in adults via machine learning.MethodsA total of 16429 men and non-pregnant women ≥ 20 years of age were analysed from five consecutive cycles of the National Health and Nutrition Examination Survey. Cohorts from years 2013-2016 (n = 6673) was used for external validation. Undiagnosed type 2 diabetes was determined by a negative response to the question "Have you ever been told by a doctor that you have diabetes?" and a positive glycaemic response to one or more of the three diagnostic tests (HbA1c > 6.4% or FPG >125 mg/dl or 2-hr post-OGTT glucose > 200mg/dl). Following comprehensive literature search, 114 potential nutritional markers were modelled with 13 behavioural and 12 socio-economic variables. We tested three machine learning algorithms on original and resampled training datasets built using three resampling methods. From this, the derived 12 predictive models were validated on internal- and external validation cohorts. Magnitudes of associations were gauged through odds ratios in logistic models and variable importance in others. Models were benchmarked against the ADA diabetes risk test.ResultsThe prevalence of undiagnosed type 2 diabetes was 5.26%. Four best-performing models (AUROC range: 74.9%-75.7%) classified 39 markers of undiagnosed type 2 diabetes; 28 via one or more of the three best-performing non-linear/ensemble models and 11 uniquely by the logistic model. They comprised 14 nutrient-based, 12 anthropometry-based, 9 socio-behavioural, and 4 diet-associated markers. AUROC of all models were on a par with ADA diabetes risk test on both internal and external validation cohorts (p>0.05).ConclusionsModels performed comparably to the chosen benchmark. Novel behavioural markers such as the number of meals not prepared from home were revealed. This approach may be useful in nutritional epidemiology to unravel new associations with type 2 diabetes.

Project description:BackgroundAlthough tiny in size and mostly harmless, spiders evoke exceptional fear in a significant part of the population and arachnophobia is one of the most common anxiety disorders with prevalence 2.7-6.1%. Two standard measures have been widely used to reliably assess the emotional and cognitive component of spider fear, the Spider Questionnaire (SPQ) and Spider Phobia Beliefs Questionnaire (SBQ). We aimed to develop and validate their Czech translations, describe distribution of spider fear in the Czech population, and analyse its association with disgust propensity and other sociodemographic characteristics.MethodsIn Phase 1, we developed Czech translations of both questionnaires using a back-translation procedure and then tested their psychometric properties against their English versions in a counterbalanced experimental design using the Mann-Whitney U test and two-sided t-test. In Phase 2, we analysed scores on the Czech SPQ and SBQ on a larger sample. We evaluated the effects of age, gender, level of education, biology background, and association with the assessments of snake fear (i.e. the Snake Questionnaire, SNAQ) and disgust propensity (i.e. the Disgust Scale-Revised, DS-R) using a Spearman correlation, redundancy analysis, and general linear models.ResultsWe have demonstrated that the Czech SPQ and SBQ are equivalent to their originals and show excellent test-retest reliability (SPQ: 0.93; SBQ: 0.87-0.90). In total, 398 (10.3%) out of 3863 subjects reached the cut-off point for potential spider phobia. In addition, SPQ and SBQ scores were highly correlated (0.73-0.79), significantly more than with the SNAQ (0.21-0.32) or the DS-R (0.36-0.40). Two multivariate statistical methods revealed a significant association between the gender, age, level of education, biology background, or disgust propensity and the SPQ scores.ConclusionThe Czech SPQ and SBQ may produce reliable and valid assessments of spider fear, but they must be further psychometrically tested considering the limitation of this study before wider use. We corroborate previous findings that fear of spiders is significantly associated with sociodemographic variables, such as gender, age, or education, as well as with the individual level of disgust propensity.

Dataset Information

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

Publications

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

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