Medicine and Health Sciences

Public defences 2021

Attend a phd defence or find the archive of concluded doctoral research

A listening ear. Psychotherapeutic interventions in the treatment of chronic, subjective tinnitus - Tinne Luyten (15/01/2021)

Tine Luyten

  • 15 January 2021
  • Time: 5PM - 7 PM
  • Supervisors: Em.Prof P. Van de Heyning, Em.Prof M. De Bodt and Prof A. Gilles
  • Language: Dutch

Abstract

The perception of tinnitus, known as an internal sound in the absence of external auditory input, can be extremely bothersome and debilitating. Worldwide, tinnitus sounds raise awareness in 8 – 20% of the population and become chronic. For about 1 – 3 %, tinnitus is distressing and therapeutic intervention is needed.

Currently, psychotherapeutic tinnitus interventions commonly consist of psychoeducation, Tinnitus Retraining Therapy (TRT) and / or Cognitive Behavioral Therapy (CBT). The tinnitus population is frequently represented with comorbid complaints such as insomnia, anxiety and depression. For this reason, there is no treatment-fits-all and thus personalized treatment options are recommended, however, to date effective treatment options are scarce. Tinnitus is known as phantom percept and recent research on Eye Movement Desensitization Reprocessing (EMDR) and phantom pain has shown promising results.

This doctoral thesis was performed in order to gain insight in the value of EMDR as treatment for chronic subjective tinnitus, to examine whether this psychotherapeutic intervention can be applied as effective tinnitus treatment, and to explore the influence of personality traits on treatment outcome.

The first part of this dissertation investigated the existence of relevant EMDR - studies. This was the first systematic review on EMDR as treatment for tinnitus resulting in an overview of the currently existing scientifically proven studies assessed by the Platinum Standard, giving support to the effectiveness of EMDR.

Consequently, in the second part of the thesis the study protocol for a prospective, randomized controlled trial with blind evaluator was represented. A total of 166 patients with chronic, subjective, non-pulsatile tinnitus were screened and 91 patients were randomized in two treatment groups: TRT/CBT versus TRT/EMDR. Data from 89 patients were assessed at three time-points i.e. before treatment, after treatment, and at three month follow up. The focus was on analyzing the Tinnitus Functional Index (TFI) as primary outcome measurement, and the Tinnitus Questionnaire (TQ), Hyperacusis Questionnaire (HQ), Hospital Anxiety and Depression Scale (HADS), Visual Analogue Scale for tinnitus loudness (VASLoudness), and Global Perceived Effect (GPE) as secondary outcomes, after psychotherapeutic treatment.

Both bimodal therapies resulted in significant reduction of tinnitus distress, tinnitus related complaints, tinnitus loudness, hypersensitivity to sound, anxiety, and depressive symptoms and led to significant increase of quality of life. Assessments indicated a stable effect of these improvements after three months. The present study provides evidence for the effectiveness of both treatment protocols showing no superiority of TRT/EMDR over TRT/CBT.

In the third part, the influence of specific personality traits in therapeutic outcome was investigated. Data from the RCT were employed to identify correlations between self-report outcome measures and Big Five Inventory (BFI) personality traits. K-means cluster analysis revealed four distinct personality clusters containing a specific combination of traits.

In conclusion, these empirical findings highlight the effectiveness of both bimodal therapies showing no different efficacy and underline the significant influence of personality traits in psychotherapeutic treatments.

New insights in connective tissue and growth disorders - Silke Peeters (14/01/2021)


Silke Peeters

  • 14 January 2021
  • Time: 3 PM - 5 PM.
  • Online defence
  • Supervisors: Prof. G. Mortier and prof. W. Van Hul

Abstract

The primary purpose of this thesis was to gain more insights in the genetic architecture and disease mechanisms underlying connective tissue and growth disorders. The first and main project focused on carpal tunnel syndrome (CTS). Although CTS is common and widely recognized, its precise etiology still remains largely unknown. In this project, we were able to delineate a new fibrillino-2-pathy by studying a family in whom CTS occurred in three subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons. Using exome sequencing, we identified a heterozygous pathogenic variant (p.Phe1670Cys) in the fibrillin-2 (FBN2) gene that co‐segregated with the phenotype in the family. We found evidence that the mutant protein affects normal integrin-mediated cell adhesion in the ECM and observed increased TGF-β signaling, resulting in fibrosis of the carpal tissues with entrapment of the median nerve as a consequence. A variant burden test in a large cohort of sporadic CTS patients revealed a significantly increased frequency of rare (6.7% versus 2.5-3.4%, p<0.001) and high-impact (6.9% versus 2.7%, p<0.001) FBN2 variants in patient alleles compared to controls. These findings strongly suggest a role of FBN2 in the pathogenesis of CTS.

The second project of this thesis focused on children born small-for-gestational age (SGA) with persisting growth failure. In a significant proportion of SGA children, the etiology of the growth failure remains unclear after routine diagnostic work-up. In this project, we investigated whether an extensive analysis of the (epi)genome can unravel the (epi)genetic cause of growth failure in a well-defined group of 20 SGA children.

We identified (likely) pathogenic variants in two siblings and two additional probands using exome sequencing. Furthermore,

SNP array analysis in all children and their parents revealed a rare, pathogenic de novo copy number variation (CNV) in two other unrelated probands. In almost all children with a genetic diagnosis, we observed an “above average” response to growth hormone treatment. These results question the relevance of the exclusion of syndromic SGA patients from growth hormone treatment. In a subgroup of 10 children, we performed a genome-wide DNA methylation assay. This analysis revealed multi-locus imprinting disturbances in two additional children. Furthermore, in the child harboring the NSD1-containing microduplication, we identified a novel DNA methylation signature. The conclusion of this second project is that a more advanced approach with deep genotyping can unravel unexpected (epi)genomic alterations in SGA children with persistent growth failure.