Parnassia Groep

Electroconvulsive therapy (ECT) is an effective treatment for major depressive episodes, though its mechanisms remain unclear. Its use is limited by stigma and potential cognitive side-effects. Repeated magnetic resonance imaging (MRI) may provide further insights into brain changes related to ECT’s efficacy and cognitive outcomes. We analyzed cognitive, efficacy, and MRI data from depressed patients undergoing ECT in two prospective longitudinal trials (NCT04028596, NL-OMON43040), using 26 matched healthy controls (2020-BC-12375) to control for test-retest effects. All participants were scanned on the same MRI system. Structural and diffusion tensor imaging (DTI) scans were acquired at baseline, after the initial ECT sessions, within two weeks post-treatment, and at three-month follow-up. Linear and nonlinear changes in grey matter (GM) volume, white matter (WM) volume, mean diffusivity (MD), and fractional anisotropy (FA) were assessed. Early brain changes were examined in relation to clinical outcomes. After the 3rd ECT session (n = 19), subcortical GM volume increased with a right-lateralized MD decrease. Two weeks post-ECT (n = 30), cortical GM volume increased, returning to baseline by three months. In WM, MD increased linearly post-ECT and remained elevated at follow-up, with no widespread FA changes (n = 30). ECT transiently impaired verbal learning (n = 23, pbonferroni = 0.04), letter fluency (n = 22, pbonferroni = 0.04), and animal fluency (n = 62, pbonferroni = 0.02). Early brain changes were not associated with cognitive or efficacy outcomes. These results suggest that ECT induces rapid changes in brain macrostructure and microstructure. While macrostructural increases are temporary, microstructural changes in brain structure are longer-lasting.

All organs in the body are covered by a layer of tightly connected cells: the epithelium. Epithelia form protective barriers while performing essential physiological functions, such as nutrient absorption in the intestine and gas exchange in the lungs. Due to constant exposure to stresses and damage, old or non-functioning cells must continuously be replaced through division of stem cells, which then give rise to the specialized cell types that control tissue function. To maintain a healthy tissue, epithelia tightly balance their rate of division, fate specification and cell loss. Traditionally, cells were shown to do this by adjusting their behavior to biochemical signals, such as growth factors. It is now clear that mechanical forces also play an essential role in this. Epithelial cells experience a variety of mechanical forces, originating from their neighbors, tissue deformations, and external sources. Cells convert these forces into intracellular biochemical responses through specialized mechanosensor proteins. In this thesis, we investigate how epithelial cells sense and respond to mechanical signals, and how mechanical control of cell behavior ensures epithelial tissue homeostasis. We first investigated the molecular mechanisms of mechanical force transduction in simple cultured epithelia. Through controlled stretch application to epithelial monolayers, we identified the intercellular signaling pathways regulated by mechanical strain. We show that forces transduced by E-cadherin-based cell-cell adhesions activate EGFR-ERK signaling by increasing ligand shedding. This demonstrates how mechanical and biochemical signals can operate within a linear cascade to regulate epithelial responses. We further uncover that epithelial tissues adjust their rate of cell division in response to fluctuations in cell density through a mechanosensitive cell cycle checkpoint. Densely packed cells experience low tensile forces, which arrests a population of cells in G2-phase of the cell cycle. These cells are readily triggered to divide when tension increases, for instance when cells are lost during wounding. These studies identify how intercellular force transduction ensures intracellular signaling regulation and homeostatic control of cell proliferation. We next extended our insight to more complex epithelia by investigating the role of forces in the homeostatic regulation of the intestinal epithelium. The intestinal epithelium is highly organized in crypt- and villus compartments respectively containing proliferating cell types and diverse specialized cell types that are renewed every 3-5 days. By controlled stretch application to intestinal organoids, we show that mechanical strain regulates intestinal cell type composition by shifting the absorptive lineage to a less mature state. Moreover, we identified that intestinal cell populations elicit distinct responses to mechanical input depending on their position in the tissue. Specifically, mechanical signals exclusively trigger calcium influx through mechanosensitive calcium channels in the crypt cells. Finally, we demonstrate that the mechanosensitive calcium channel PIEZO is essential for intestinal stem cell maintenance and function, thus playing a crucial role in preserving intestinal tissue homeostasis. Together, this work reveals how mechanical forces regulate epithelial behavior through integration of molecular, cellular, and tissue-level processes. These findings advance our understanding of epithelial homeostasis and provide a conceptual framework for investigating how dysregulation of mechanoresponses may contribute to disease.

An important aim of the new mental health act implemented in the Netherlands in 2020 was to shift the focus from hospitalization to treatment. The act provides an option for patients' compulsory treatment at home (CTH). Unlike compulsory community treatment (CCT), which allows mental health workers to hospitalize patients involuntarily if they do not comply with treatment. CTH is not provided elsewhere in the world. This case report concerns a patient who, to avoid hospitalization, received CTH in the form of compulsory medication and was able to recover at home. Retrospectively, she and the mental health team both positively evaluated this use of CTH. The parties involved all concluded that CTH restricted the patient's autonomy less than hospitalization, it did not influence the therapeutic relationship, and the CTH could be delivered in a way that it did not compromise participants' safety. This case report shows that, in some situations, CTH can avoid hospitalization. Care should nonetheless be taken to assess its appropriateness, to discuss any preconditions, and to evaluate the use of compulsory treatment in dialog with the patient and significant others.

ABSTRACTObjectiveA significant proportion of patients with eating disorders (EDs) also meet criteria for posttraumatic stress disorder (PTSD). Guidelines recommend exposure‐based treatments for PTSD, including prolonged exposure (PE) and eye movement desensitisation and reprocessing (EMDR). Investigating therapist‐related factors could lead to improve their use when ED and PTSD co‐occur.MethodA cross‐sectional survey was conducted among 81 EDs therapists (88% female; M age = 40.4, SD = 10.4) in 2023 in the Netherlands. Hierarchical multiple regression analyses assessed predictors of excluding patients with EDs and comorbid PTSD from exposure‐based treatments for PTSD.ResultsTherapists held more favourable beliefs about EMDR (M = 10.5, SD = 7.5) than PE (M = 13.9, SD = 6.9), and were less likely to exclude patients with EDs and comorbid PTSD from EMDR (M = 15.5, SD = 9.3) than PE (M = 17.7, SD = 9.3) (t(80) = 3.47, p < 0.002). Beliefs about exposure‐based interventions predicted the likelihood of exclusion from both PE (β = 0.56, p < 0.002) and EMDR (β = 0.69, p < 0.002).ConclusionsTherapists' beliefs influence the use of exposure‐based treatments for PTSD in patients with EDs and comorbid PTSD. Addressing these beliefs in training, may support broader implementation.

BackgroundSocial functioning, symptoms, cognition and well-being are all considered important recovery domains for patients with schizophrenia spectrum disorders (SSD). In the current study, we investigated to what extent longitudinal changes in one recovery domain moderated changes in another recovery domain, and which personal, clinical or social patient characteristics influence changes in recovery domains for patients with SSD.MethodsWe investigated data from GROUP, a prospective, longitudinal six-year study of patients with SSD. We analyzed longitudinal changes in 15 outcomes (i.e., subdomains of symptoms, social functioning, cognition, quality of life or well-being), through a linear mixed-effects model analysis. Changes in other outcomes, patients’ duration of illness (DOI), and personal, clinical, or social patient characteristics at baseline were treated as covariates in the analyses.ResultsWe observed long-term improvement in all outcomes, except for depressive symptoms and subjective well-being. Larger improvements in positive symptoms, social functioning and executive functioning were indicated for patients with a short DOI. We found multiple, moderating effects, mainly for patients with a short DOI, between changes in cognition, social functioning, symptoms and quality of life. Limited moderating effects were indicated between these recovery domains and well-being. Baseline levels of outcomes, schizophrenia diagnosis, education level, ethnicity, living situation, employment status and marital status were all moderators for changes in most outcomes.ConclusionsSymptoms, social functioning, cognition and quality of life often concurrently improved over the course of SSD. These longitudinal changes were mostly driven by social patient characteristics, such as education level, ethnicity, living situation, employment status and marital status.Clinical trial numberNot applicable.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-025-07700-8.

Metabolic syndrome is a growing public health problem in Indonesia and is closely linked to an unbalanced diet and lack of physical activity. This condition directly impacts the high incidence of hyperglycemia, dyslipidemia, and other metabolic disorders at the community level. Therefore, this community service program was implemented to improve nutritional literacy and public awareness of the importance of physical activity through basic health checks and education on healthy lifestyles. The implementation method included participant registration, blood sugar, uric acid, and cholesterol levels were checked, interactive education on a balanced nutritional diet was provided, and changes in participant knowledge and attitudes were measured. The results showed that some participants had relatively high blood sugar and cholesterol levels, particularly among women, while men tended to have higher uric acid levels. The education provided increased participants' understanding of the risks of metabolic syndrome and encouraged changes in attitudes towards diet and daily physical activity. Overall, this activity successfully raised participants' awareness of the importance of metabolic syndrome prevention. These findings confirm that health check-based education is an effective approach to changing behavior and can be developed into a sustainable program at the community level.

The Dutch Pharmacogenetics Working Group (DPWG) describes gene-drug interactions to facilitate pharmacogenetic implementation in clinical practice. The current guideline describes the gene-drug interactions for TPMT, NUDT15 and thiopurines (azathioprine, 6-mercaptopurine and thioguanine). Evidence based recommendations were obtained via a literature review of published studies. This literature review showed that gene variants leading to a decreased activity of TPMT and/or NUDT15 result in higher risk of toxicities, especially bone-marrow depression. For intermediate metabolisers (IM) of TPMT or NUDT15, it is advised to start with 50% of the normal dose when treated with azathioprine or 6-mercaptopurine. For poor metabolisers (PM), it is advised to start with an alternative treatment or to reduce the dose to 10% of the normal dose. For thioguanine, a dose of 75% of the normal dose is advised for TPMT IM and 50% of the normal dose for NUDT15 IM. Alternative treatment or a start dose reduction is advised for PM. A start dose of 6-7% can be used for TPMT PM and of 10% for NUDT15 PM. For TPMT or NUDT15 IM treated for leukaemia, starting with the normal dose can be considered and then decrease the dose to the advised dose described above in case toxicities occur. For NUDT15 PM reduced starting dose is advised only if an alternative is not possible, due to a higher uncertainty in the calculated dose reduction for NUDT15 PM than for TPMT PM.DPWG classifies genotyping for TPMT and NUDT15 "essential" before thiopurine initiation.

The objective of this study was to understand how socio-economic disadvantages relate to mental health problems (MHP) among children with mild intellectual disability or borderline intellectual functioning (MID-BIF) in outpatient care by extending beyond traditional economic measures, incorporating cumulative risks, and analyzing variations across clinical subgroups. Using a population-based case-control design, data from Statistics Netherlands and mental health records were analyzed for 1,742 children with MID-BIF receiving mental health care (Mage = 9.6, 33.1% girls) and 8,710 age- and sex-matched controls aged 0-17. Logistic regression revealed that children with MID-BIF and MHP were significantly more likely than controls to come from families facing socio-economic disadvantages, such as single parenthood, lower parental education, reliance on social benefits, low income, and subsidized housing. Socio-economic risks were more likely to cluster in the case group, with 15.3% of children exposed to five risk categories and 6.7% to all six, compared to 6.7% and 3.6% in controls, respectively. Children in the internalizing and externalizing symptom-based groups faced more pronounced socio-economic disadvantages than those in the developmental group. Additionally, more extensive care was unexpectedly linked to more favorable socio-economic conditions, suggesting a complex interplay between care needs and socio-economic conditions. Taken together, this study showed that children with MID-BIF receiving outpatient care for their MHP often face greater and more clustered socio-economic disadvantages. Simultaneously, children from socio-economically disadvantaged backgrounds received less specialized mental health care. This underscores the importance of addressing barriers in mental health care and promoting family- and community-based care.

Previous research has highlighted the negative impact of the COVID-19 pandemic on healthcare workers’ (HCWs) mental health, yet protective factors remain underexplored. Emerging studies emphasize the importance of trust in government and interpersonal relationships in reducing infections and fostering positive vaccine attitudes. This study investigates the relationship between HCWs’ trust in the workplace and government and depressive symptoms during the pandemic. The COVID-19 HEalth caRe wOrkErS study surveyed 32,410 HCWs from 22 countries, including clinical and nonclinical staff. Participants completed the Patient Health Questionnaire-9 and ad-hoc questions assessing trust in the workplace and government. Logistic regression and multilevel models examined associations between trust levels and depressive symptoms. High workplace trust (OR = 0.72 [0.68, 0.76]) and government trust (OR = 0.72 [0.69, 0.76]) were linked to lower odds of depressive symptoms, with significant between-country variation. Country-level analyses showed that workplace trust was more protective in more developed countries and under stricter COVID-19 restrictions. Despite cross-country variation, HCWs with higher trust in the workplace and government had ~28% lower odds of experiencing depressive symptoms compared to those with lower trust. Promoting trust may help mitigate the mental health impact of future crises on HCWs.

BackgroundAfter remission of a first-episode psychosis (FEP), antipsychotic discontinuation is associated with an increased risk of relapse compared to maintenance treatment. We studied short and longer-term effects of discontinuation of D2 receptor (D2R) antagonist and partial agonist antipsychotics on striatal dopamine D2/3R availability in FEP patients.MethodsRemitted FEP patients underwent two [11C]raclopride PET scans to measure striatal D2/3R availability: 1 week after antipsychotic discontinuation (n = 16 antagonist users, n = 6 partial agonist users) and after being medication free for 6–8 weeks (n = 8 antagonist users, n = 5 partial agonist users). Fifteen matched healthy controls were scanned once. Psychotic relapse was monitored up to 12 months after discontinuation.ResultsOne week after discontinuation, D2R antagonist discontinuers showed higher striatal binding potential (BPND) than partial D2R agonist discontinuers (p < 0.001, CI = 0.749 to 1.681) and controls (p = 0.045, CI = 0.008 to 0.708), while partial agonist discontinuers had significantly lower BPND than controls (p = 0.001, CI = -1.326 to -0.386). 6-8 weeks after discontinuation, former antagonist users showed similar BPND to controls (p > 0.25), whereas former partial agonist users had higher BPND than controls (p = 0.027, CI = 0.069 to 1.085). Participants who discontinued antagonists relapsed more often (81%) than those who discontinued partial agonists (17%)(χ2 = 5.32, p = 0.021).ConclusionsDiscontinuation of partial D2R agonists may affect D2/3R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.