Research Livia De Picker

Abstract

BACKGROUND: 30% of Major Depression Disorder patients display an immune-mediated subtype, associated with poor response to first-line antidepressant treatments. Immune-targeted augmentation with anti-inflammatory compounds shows promise and may be more effective for the immune-mediated subgroup. For optimal clinical trial designs, we require guidance on the selection of patients who may benefit, the outcome measures that capture the clinical benefits, and the subtype-specific effect sizes per compound. AIM: Identify baseline predictive blood-based and clinical biomarkers, define the optimal outcome measures for immune-targeted interventions, and rank these based on subtype-specific effect sizes. Facilitate science-to-policy translation by integrating research findings into clinical recommendations and predictive enrichment strategies for future clinical trials. APPROACH: I will address these questions through a dual approach, integrating insights (WP3) gained with stratification meta-analyses and individual participant data (of at least n=10 RCTs) (WP1) with the results of our pre-stratified clinical trial (WP2). IMPACT: My project will innovate MDD treatment guidelines and optimise future RCT protocols. This will result in a decreased number of failed RCTs, which will lead to cost-effective benefits and more interest among pharmaceutical industry players. The predictive enrichment strategies can then be used to innovate intervention trials also in other mental disorders.

Researcher(s)

• Promoter: De Picker Livia
• Co-promoter: Morrens Manuel
• Fellow: Wessa Céline

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project type(s)

• Research Project

Abstract

In 2018, 6% of people over the age of 15 had a depressive disorder in the Flemish Region (Statistiek Vlaanderen). In 2019, this was 36 million people per year for Europe, good for 92 billion euros in annual costs (WHO Global Burden of Disease 2019). The WHO estimates that depression will be one of the leading causes of disease burden by 2030. Depression, however, is very heterogeneous, with an estimate of 33-40% responding poorly or not at all to gold standard treatment. Innovation in the field of treatment could therefore have a major impact for this subgroup. This project aims to repurpose two established anti-inflammatory compounds as adjuvant therapy for immune-mediated depression, in line with state-of-the-art research of the last 10 years. Immune-mediated depression represents a subtype which accounts for approximately 30% of depressive disorders (Osimo et al., 2019). Patients with this immunosubtype are more likely to have a higher severity of depression, a lower quality of life and more somatic symptoms (Foley et al., 2021). Furthermore, it is accompanied by a high incidence of treatment resistance (Carvalho et al., 2013). While their mechanisms of action completely differ from those of existing antidepressant treatment options, immunomodulatory drugs celecoxib and minocycline have proven their merit as add-on treatment in depressive episodes. They have been on the Belgian market for years and come with a known pharmacological and safety profile. Patient stratification at baseline based on inflammatory status will reveal which inflammatory subpopulation benefits most from each of the two investigated anti-inflammatory compounds. Additionally, our distinctive study design allows head-to-head comparison of both add-on therapies and will as such provide the last stepping stones towards clinical implementation of individualised treatment strategies in depression. The novelty and clinical relevance of this project reside in (1) the direct comparison of each compound separately as well as (2) the selection of patients who may benefit from anti-inflammatory treatment via stratification based on baseline inflammatory levels. Hence, this project will tackle a knowledge gap vital for the development of clinical practice guidelines. The addition of this treatment option to the psychiatric arsenal and the inflammation-based stratification prior, opens the way to a pragmatic strategy in the form of personalised medicine in biological psychiatry. This could support and optimise the choice of psychiatric treatment, thus limiting exposure to ineffective treatments and shortening the length of hospital stay. As a result, this repurposing strategy will significantly reduce the associated health care costs, without the additional costs associated with bringing new compounds to market. Objectives Validate the efficacy of immune-targeted augmentation with minocycline or celecoxib in a Flemish cohort of patients with MDD who failed to remit with one or two trials of antidepressant treatment; Compare the respective acceptability, treatment response and remission rates of minocycline and celecoxib as adjunctive therapy; Compare the efficacy of both compounds as adjunctive therapy in an immune-mediated subtype of MDD versus an unstratified patient sample; Evaluate the use of hsCRP as a predictor for treatment response to minocycline and celecoxib.

Researcher(s)

• Promoter: Morrens Manuel
• Co-promoter: De Picker Livia
• Co-promoter: Van Royen Paul

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project website

Project type(s)

• Research Project

Abstract

Description: Several studies have shown that rapid-eye-movement (REM) sleep plays an essential role in the processing of emotions (Wassing et al., 2016). Research suggests that restless REM sleep reflects a process that impedes overnight resolution of emotional distress (Wassing et al. 2019). This finding is relevant when evaluating the effect that REM sleep fragmentation has in a population with severe emotional dysregulation problems, such as Borderline Personality Disorder (BPD). Particularly, as it has been shown that there is an association between subjective sleep disturbance and recovery status among BPD patients (Plante et al., 2013). This research project aims to investigate the effect that fragmented REM has on the down regulation of emotional distress in a clinical exploratory study of patients with severe emotion dysregulation, in particular borderline personality disorder. The methods of this research will include polysomnography, psychometric testing and additional (neuro)biological measures. This project will involve literature search, preparation of a doctoral thesis, contribution to research and teaching at CAPRI (Universiteit Antwerpen) en SINAPS (UPC Duffel. Coordination, management and quality assurance of the project, as well as the management of the contact with the participants and clinical health care staff of the involved hospitals (UPC Duffel and KARUS Gent). Active participation in the development of a plan for further implementation and distribution of the results of the project as well as the publication of scientific articles related to the research project of the assignment. The studies derived from this PhD appointment will be conducted in the Universiteit Antwerpen at the Department of Psychiatry, Faculty of Medicine. Research will be conducted at the Collaborative Antwerp Research Institute (CAPRI) (https://www.uantwerpen.be/en/research-groups/capri/) in combination with the Scientific Initiative for Neuropsychiatric and Psychopharmacological Studies (SINAPS) in Duffel (https://www.sinapsduffel.com/ ). Research participants recruitment will be conducted at the UPC Duffel Hospital (https://www.pz-duffel.be/ ) and the KARUS Gent Hospital (https://www.karus.be/t).

Researcher(s)

• Promoter: Morrens Manuel
• Co-promoter: De Picker Livia
• Fellow: Mendoza Alvarez Mariana

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project type(s)

• Research Project

Abstract

The course of bipolar disorder (BD) is influenced by several factors. Experiential avoidance (EA) and positive rumination (PR) are two constructs whose presence and impact on BD have been studied to a limited extent. EA refers to not wanting to face one's own experiences, e.g. emotions, thoughts, bodily sensations. In this case, one will take action to reduce, change or avoid these experiences, despite negative consequences (Hayes, Wilson, Gifford, & Follette, 1996; Hayes et al., 2004). In PR, people will respond to positive affect with thoughts about their own positive experiences, traits or life circumstances (Feldman, Joormann, & Johnson, 2007). In the present longitudinal study, patients are compared to healthy controls in terms of presence of PR and EA. The antecedents of EA are examined, as well as the relationship between EA and PR. Possible negative consequences of EA and PR, such as duration of mood disturbance and current psychological and somatic symptoms are also investigated.

Researcher(s)

• Promoter: Morrens Manuel
• Co-promoter: De Picker Livia
• Fellow: Gauwloos Tatjana

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: De Picker Livia

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Sabbe Bernard
• Fellow: De Picker Livia

Research team(s)

• Collaborative Antwerp Psychiatric Research Institute (CAPRI)

Project type(s)

• Research Project