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Abstract Background Persistent depressive disorder (PDD) is prevalent and debilitating. For patients with PDD, psychiatric rehabilitation using self-management interventions is advised as the next therapeutic step after multiple unsuccessful treatment attempts. The “Patient and Partner Education Program for All Chronic Diseases” (PPEP4All) is a brief, structured self-management program that focuses on functional recovery for patients and their partners/caregivers. In chronic somatic disorder populations, PPEP4All has already been shown to be clinically effective. We examined whether PPEP4All adapted for PDD (PPEP4All-PDD, nine weekly group or individual sessions) is also clinically effective for adults/elderly with PDD and their partners/caregivers compared to care-as-usual (CAU) in specialized mental healthcare. Methods In this mixed-method multicenter pragmatic randomized controlled trial, 70 patients with PDD and 14 partners/caregivers were allocated to either PPEP4All-PDD (patients, n = 37; partners/caregivers, n = 14) or CAU (patients, n = 33; partners/caregivers, not included) and completed questionnaires at 0, 3, 6, and 12 months regarding depressive symptoms, psychopathology, psychosocial burden, mental resilience, and happiness/well-being. Qualitative data were collected regarding treatment satisfaction. Data were analyzed using mixed model analyses and an intention-to-treat (ITT) approach. Results There was no statistically significant difference in any outcome regarding clinical effectiveness between PPEP4All-PDD and CAU. Subgroup analysis for depressive symptoms did not show any interaction effect for any subgroup. Although 78% of participants recommended PPEP4All-PDD, there was no difference in treatment satisfaction between PPEP4All-PDD (score = 6.6; SD = 1.7) and CAU (score = 7.6; SD = 1.2), p = 0.06. Conclusion Although depressive symptoms did not improve relative to CAU, this only confirmed that treatment for patients with treatment-resistant PDD should move from symptom reduction to functional recovery. Also, functional recovery may be reflected in other outcomes than psychosocial burden, such as self-empowerment, in patients with treatment-resistant PDD. Future research on PPEP4All-PDD could focus on a longer-term program and/or online program that may also be offered earlier in the treatment process as an empowerment intervention. Trial registration Netherlands Trial Register Identifier NL5818. Registered on 20 July 2016 https://clinicaltrialregister.nl/nl/trial/20302

Background: Healthcare workers (HCW) have faced unprecedented challenges during the COVID-19, with significant impact on their well-being. We aimed to monitor stress-related symptoms and resilience in HCW over time in relation to various factors during the COVID-19 pandemic. Methods: Between June 2020 and May 2022, data was collected among HCW of Leiden University Medical Centre (LUMC) through a digital self-monitoring application. The application included a 14-items self-monitoring tool (i.e., 7-items on Supporting factors, 7-items on Stressful burden), and a set of validated questionnaires (i.e., the Copenhagen Burnout Inventory (CBI), Impact of Event Scale – Revised (IES-R), Resilience Evaluation Scale (RES), and Depression Anxiety and Stress Scale (DASS-21). Results: The self-monitoring tool and validated questionnaires were completed by 1070 and 413 participants respectively. Mean stress-related symptom scores (as measured by the self-monitoring, CBI, IES-R, and DASS-21) exhibited significant changes over time (all p’s < 0.001), which correlated with the waves of COVID-19 patients admitted and the national COVID-19 mortality rate (all p’s < 0.005). Resilience, as measured by the RES, showed a significant decrease from the start of data collection onwards (p = 0.001), whereas supporting factors showed significant decreases the first few months, followed by fluctuations after January 2021 (p = 0.02). Limitations: Selection bias may have arisen as those participating may have been more concerned with the burden on mental wellbeing. Conclusions: The current study underscores the need for active psychosocial support for all HCW particularly during periods of increased admissions due to pandemics.

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Abstract Background After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the “Patient and Partner Education Program for All Chronic Illnesses” (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers. Methods Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months. Discussion This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers. Trial registration Netherlands Trial Register Identifier NTR5973 . Registered on 20 July 2016.

Abstract Background Population segmentation and risk stratification are important strategies for allocating resources in public health, health care and social care. Social exclusion, which is defined as the cumulation of disadvantages in social, economic, cultural and political domains, is associated with an increased risk of health problems, low agency, and as a consequence, a higher need for health and social care. The aim of this study is to test social exclusion against traditional social stratifiers to identify high-risk/high-need population segments. Methods We used data from 33,285 adults from the 2016 Public Health Monitor of four major cities in the Netherlands. To identify at-risk populations for cardiovascular risk, cancer, low self-rated health, anxiety and depression symptoms, and low personal control, we compared relative risks (RR) and population attributable fractions (PAF) for social exclusion, which was measured with the Social Exclusion Index for Health Surveys (SEI-HS), and four traditional social stratifiers, namely, education, income, labour market position and migration background. Results The analyses showed significant associations of social exclusion with all the health indicators and personal control. Particular strong RRs were found for anxiety and depression symptoms (7.95) and low personal control (6.36), with corresponding PAFs of 42 and 35%, respectively. Social exclusion was significantly better at identifying population segments with high anxiety and depression symptoms and low personal control than were the four traditional stratifiers, while the two approaches were similar at identifying other health problems. The combination of social exclusion with a low labour market position (19.5% of the adult population) captured 67% of the prevalence of anxiety and depression symptoms and 60% of the prevalence of low personal control, as well as substantial proportions of the other health indicators. Conclusions This study shows that the SEI-HS is a powerful tool for identifying high-risk/high-need population segments in which not only ill health is concentrated, as is the case with traditional social stratifiers, but also a high prevalence of anxiety and depression symptoms and low personal control are present, in addition to an accumulation of social problems. These findings have implications for health care practice, public health and social interventions in large cities.

Background Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems. Aims To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients. Method The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale – Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events. Results In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74–1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65–1.19), with a rate ratio of 1.08 (95% CI 0.67–1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes. Conclusions Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients.

Introduction: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. Latent T. gondii infection has been linked to several neuropsychiatric mood disorders and behaviors. The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. Methods: In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n ​= ​133), anxiety (n ​= ​188), comorbid depressive and anxiety (n ​= ​148), and remitted disorders (n ​= ​889), as well as in healthy controls (n ​= ​373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. Results: Participants were on average 51.2 years (SD ​= ​13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69-1.28). Conclusions: No evidence was found for a relationship between affective disorders and T. gondii infection in the current sample.

Abstract Background Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes. Methods Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses). Results With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes. Conclusions Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate.

Abstract Background Social exclusion (SE) refers to the inability of certain groups or individuals to fully participate in society. SE is associated with socioeconomic inequalities in health, and its measurement in routine public health monitoring is considered key to designing effective health policies. In an earlier retrospective analysis we demonstrated that in all four major Dutch cities, SE could largely be measured with existing local public health monitoring data. The current prospective study is aimed at constructing and validating an extended national measure for SE that optimally employs available items. Methods In 2012, a stratified general population sample of 258,928 Dutch adults completed a version of the Netherlands Public Health Monitor (PHM) questionnaire in which 9 items were added covering aspects of SE that were found to be missing in our previous research. Items were derived from the SCP social exclusion index, a well-constructed 15-item instrument developed by the Netherlands Institute for Social Research (SCP). The dataset was randomly divided into a development sample (N =129,464) and a validation sample (N = 129,464). Canonical correlation analysis was conducted in the development sample. The psychometric properties were studied and compared with those of the original SCP index. All analyses were then replicated in the validation sample. Results The analysis yielded a four dimensional index, the Social Exclusion Index for Health Surveys (SEI-HS), containing 8 SCP items and 9 PHM items. The four dimensions: “lack of social participation”, “material deprivation”, “lack of normative integration” and “inadequate access to basic social rights”, were each measured with 3 to 6 items. The SEI-HS showed adequate internal consistency for both the general index and for two of four dimension scales. The internal structure and construct validity of the SEI-HS were satisfactory and similar to the original SCP index. Replication of the SEI-HS in the validation sample confirmed its generalisability. Conclusion This study demonstrates that the SEI-HS offers epidemiologists and public health researchers a uniform, reliable, valid and efficient means of assessing social exclusion and its underlying dimensions. The study also provides valuable insights in how to develop embedded measures for public health surveillance.

BackgroundThe recently developed Social Exclusion Index for Health Surveys (SEI-HS) revealed particularly strong social exclusion in non-Western immigrant groups compared to the native Dutch population. To qualify such results, cross-cultural validation of the SEI-HS in non-Western immigrant groups is called for.MethodsA sequential explanatory mixed methods design was used, employing quantitative data from the Netherlands Public Health Monitor along with qualitative interviews. Data from 1,803 adults aged 19 years or older of Surinamese, 1,009 of Moroccan and 1,164 of Turkish background and 19,318 native Dutch living in the four largest cities in the Netherlands were used to test the factorial structure of the SEI-HS and differential item functioning across immigrant groups. Additionally, 52 respondents with a high score on the SEI-HS and from different background were interviewed on the item content of the SEI-HS and subjective feelings of exclusion. For each SEI-HS item the semantic, conceptual and contextual connotations were coded and compared between the immigrant groups and native Dutch.ResultsHigh levels of social exclusion were found in 20.0% of the urban population of Surinamese origin, 20.9% of Moroccan, 28.7% of Turkish and 4.2% of native Dutch origin. The 4-factor structure of the SEI-HS was confirmed in all three immigrant groups. None of the items demonstrated substantial differential item functioning in relation to immigration background. The interviews uncovered some methodological shortcomings, but these did not substantially impact the observed excess of social exclusion in immigrant groups.ConclusionsThe present study provides evidence in support of the validity of the SEI-HS in adults of Surinamese, Moroccan and Turkish background and confirms the major social exclusion of these immigrant groups in the main cities in the Netherlands. Policy measures to enhance social inclusion and reduce exclusion are urgently needed.

INTRODUCTION: Social exclusion is considered a major factor in the causation and maintenance of health inequalities, but its measurement in health research is still in its infancy. In the Netherlands the Institute for Social Research (SCP) developed an instrument to measure the multidimensional concept of social exclusion in social and economic policy research. Here, we present a method to construct a similar measure of social exclusion using available data from public health surveys. METHODS: Analyses were performed on data from the health questionnaires that were completed by 20,877 adults in the four largest cities in the Netherlands. From each of the four questionnaires we selected the items that corresponded to those of the SCP-instrument. These were entered into a nonlinear canonical correlation analysis. The measurement properties of the resulting indices and dimension scales were assessed and compared to the SCP-instrument. RESULTS: The internal consistency of the indices and most of the dimension scales were adequate and the internal structure of the indices was as expected. Both generalisabiliy and construct validity were good: in all datasets strong associations were found between the index and a number of known risk factors of social exclusion. A limitation of content validity was that the dimension "lack of normative integration" could not be measured, because no relevant items were available. CONCLUSIONS: Our findings indicate that a measure for social exclusion can be constructed with available health questionnaires. This provides opportunities for application in public health surveillance systems in the Netherlands and elsewhere in the world.