In this thesis, we used qualitative and quantitative research methods to gain insight in treatment decision-making for depression- and anxiety disorders in specialized mental health care. We... Show moreIn this thesis, we used qualitative and quantitative research methods to gain insight in treatment decision-making for depression- and anxiety disorders in specialized mental health care. We identified what factors are important in the decisional process, to both patients and clinicians, and how they determine decision-making outcomes, i.e., the decision to opt for: pharmacotherapy, psychotherapy, or a combination of both. We determined what preferences patients and clinicians have regarding the treatment of depression and anxiety disorders, which treatments are selected, and which factors are involved in the formation of such treatment preferences and treatment selection. Additionally, we determined what preferences patients and clinicians have regarding their role in the decisional process, their experienced decision-making roles, and the level of concordance between preferred and experienced role of patients. Finally, we examined the extent of Shared Decision-Making (SDM) in clinical practice and explored possible target points to improve SDM. Show less
De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. Show less
It is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large... Show moreIt is well known that military deployment can lead to mental health problems in veterans, but the long-term impact is still unclear. This thesis discusses the results of the PRISMO-study, a large cohort study in a group of Dutch Afghanistan veterans with a follow-up period of ten years. It shows that at ten years post-deployment, 8% of the cohort reported severe symptoms of posttraumatic stress disorder (PTSD). Agoraphobia, anxiety, depression, and hostility symptoms are also reported more frequently at ten years post-deployment compared to pre-deployment. Furthermore, this thesis demonstrates the large heterogeneity in PTSD symptom development among veterans. Of note is the delayed onset group that experienced increasing symptom levels between five and ten years post-deployment and did not show significant symptom reduction. The results from this thesis also show that various psychological factors, such as social support, and biological factors, such as DNA methylation, are associated with the development of PTSD or other mental health symptoms after deployment. Combining these factors in a prediction model for PTSD symptoms has not led to a useful screening instrument. It does, however, offer important leads for the identification of risk factors for PTSD and the development of intervention programs. Show less
Background Depression and anxiety are common mental disorders among patients with chronic pain. It is hypothesised that patients suffering from these disorders benefit less from cervical spine... Show moreBackground Depression and anxiety are common mental disorders among patients with chronic pain. It is hypothesised that patients suffering from these disorders benefit less from cervical spine surgery than mentally healthy patients. Therefore, this study aimed to quantify the effect of mental health status on functional outcome after anterior cervical discectomy in a post hoc analysis on RCT data. Methods One hundred eight patients from the NECK trial, with radiculopathy due to a one-level herniated disc, underwent anterior cervical discectomy and were included into this analysis. Functional outcome was quantified using the Neck Disability Index (NDI), and mental health status was measured using the Hospital Anxiety and Depression Score (HADS) questionnaire. NDI differences were assessed using generalised estimated equations (GEE), crude means, a predictive linear mixed model (LMM) using baseline scores and over time with an explanatory LMM. Results At baseline, 24% and 32% of patients were respectively depressed and anxious and had statistically significant and clinically relevant higher NDI scores during follow-up. However, in those patients in which the HADS returned to normal during follow-up, NDI values decreased comparably to the non-depression or non-anxiety cases. Those patients that demonstrated persisting high HADS values had convincingly worse NDI scores. A predictive LMM showed that combining baseline NDI and HADS scores was highly predictive of NDI during follow-up. The R shiny application enabled the effective, visual communication of results from the predictive LMM. Conclusion This study shows that mental health status and disability are strongly associated and provides insight into the size of the effect, as well as a way to use this relation to improve preoperative patient counselling. These findings give rise to the suggestion that incorporating mental health screening in the preoperative assessment of patients could help to adequately manage patients' expectations for functional recovery. Show less
Hebbrecht, K.; Morrens, M.; Giltay, E.J.; Nuijs, A.L.N. van; Sabbe, B.; Ameele, S. van den 2021
Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway... Show moreIntroduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship. Show less
Roelofs, E.F.; Bas-Hoogendam, J.M.; Werff, S.J.A. van der; Valstar, S.D.; Wee, N.J.A. van der; Vermeiren, R.R.J.M. 2021
Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies... Show moreCross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12-18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months' time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents. Show less
Galbally, M.; Watson, S.J.; Lappas, M.; Kloet, E.R. de; Rossum, E. van; Wyrwoll, C.; ... ; Lewis, A.J. 2021
Placental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental... Show morePlacental 11fl-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental health via placental 11flHSD2 mRNA to cortisol regulation in the infant offspring. This study reports on data obtained from 236 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). At term, placental tissue was collected within 30 min of birth from 52 participants meeting current criteria for a depressive disorder, and 184 control participants. Depressive disorders were diagnosed using the SCID-IV. In addition, antidepressant use, depressive and anxiety symptoms were measured in early and late pregnancy. Placental 11fl-HSD2 mRNA expression was measured using qRT-PCR. Infant salivary cortisol samples were taken at 12 months of age. Women on antidepressant medication and with higher trait anxiety had higher placental 11fl-HSD2 expression compared to women not taking medication. Furthermore, the offspring of women taking an antidepressant and who also had a current depressive disorder and high trait anxiety had high cortisol reactivity at 12 months of age and this was mediated through 11fl-HSD2 mRNA expression. In contrast, offspring of women not taking antidepressant medication with depressive disorder and high anxiety there was low cortisol reactivity observed. Our findings suggest that the relationship between maternal antenatal depression and anxiety and infant cortisol reactivity is mediated through placental 11fl-HSD2 mRNA expression. Furthermore, the direction differed for women taking antidepressants, where infant cortisol reactivity was high whereas when compared to those with unmedicated depression and anxiety, where infant cortisol reactivity was low. Show less
Objective: To determine the physical and mental health of very old people (aged 80+) with anaemia.Methods: Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ... Show moreObjective: To determine the physical and mental health of very old people (aged 80+) with anaemia.Methods: Individual level meta-analysis from five cohorts of octogenarians (n = 2,392): LiLACS NZ Maori, LiLACS NZ non-Maori, Leiden 85-plus Study, Newcastle 85+ Study, and TOOTH. Mixed models of change in functional ability, cognitive function, depressive symptoms, and self-rated health over time were separately fitted for each cohort. We combined individual cohort estimates of differences according to the presence of anaemia at baseline, adjusting for age at entry, sex, and time elapsed. Combined estimates are presented as differences in standard deviation units (i.e. standardised mean differences-SMDs).Results: The combined prevalence of anaemia was 30.2%. Throughout follow-up, participants with anaemia, on average, had: worse functional ability (SMD -0.42 of a standard deviation across cohorts; CI -0.59, -0.25); worse cognitive scores (SMD -0.27; CI -0.39,-0.15); worse depression scores (SMD -0.20; CI -0.31, -0.08); and lower ratings of their own health (SMD -0.36; CI -0.47,-0.25). Differential rates of change observed were: larger declines in functional ability for those with anaemia (SMD -0.12 over five years; CI -0.21, -0.03) and smaller mean difference in depression scores over time between those with and without anaemia (SMD 0.18 over five years; CI 0.05, 0.30).Conclusion: Anaemia in the very old is a common condition associated with worse functional ability, cognitive function, depressive symptoms, and self-rated health, and a more rapid decline in functional ability over time. The question remains as to whether anaemia itself contributes to worse outcomes or is simply a marker of chronic diseases and nutrient deficiencies. Show less
Galbally, M.; Watson, S.J.; IJzendoorn, M. van; Saffery, R.; Ryan, J.; Kloet, E.R. de; ... ; Lewis, A.J. 2020
Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early... Show moreUnderstanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes. Show less
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
Background Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with... Show moreBackground Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. Methods This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of >= 10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. Discussion If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. Show less
Understanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes.... Show moreUnderstanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes. The aim of this study was to investigate infant and maternal cortisol in women with depression. Data were obtained from 241 pregnant women within the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort study. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeat Edinburgh Postnatal Depression Scale (EPDS). Repeated measures of antidepressant use, stressful events, anxiety symptoms and maternal hair cortisol concentrations (HCC) and infant cortisol at 12 months postpartum in saliva and hair. Socio-emotional outcomes were measured at 12 months by maternal report on the Brief Infant and Toddler Socio-emotional Assessment (BITSEA). This study found that maternal depression was not associated with maternal HCC. Anxiety, stress and antidepressant use were not associated with maternal HCC. Independently, higher maternal 3rd trimester maternal depressive and anxiety symptoms were associated with lower infant cortisol response at 12 months of age. A higher number of postpartum stressful events was associated with lower infant cortisol response. Lower infant stress reactivity was associated with higher externalizing symptoms at 12 months of age. Future studies are required to understand implications for later mental health. Show less
Aim: To identify moderators of treatment effect for Mindfulness-Based Cognitive Therapy (MBCT) versus Treatment As Usual (TAU) in depressed patients.Methods: An individual patient data-analysis was... Show moreAim: To identify moderators of treatment effect for Mindfulness-Based Cognitive Therapy (MBCT) versus Treatment As Usual (TAU) in depressed patients.Methods: An individual patient data-analysis was performed on three randomized-controlled trials, investigating the effect of MBCT + TAU versus TAU alone (N = 292). Patients were either in (partial) remission, currently depressed or had chronic, treatment-resistant depression. Outcomes were depressive symptoms and quality of life. The Qualitative INteraction Trees (QUINT) method was used to identify subgroups that benefited more from either condition.Results: MBCT + TAU outperformed TAU in reducing depressive symptoms. For both conditions, the effect of baseline depressive symptoms on post-treatment depressive symptoms was curvilinear. QUINT analyses revealed that MBCT + TAU was more beneficial than TAU for patients with an earlier onset and higher rumination levels in terms of depressive symptom reduction and for patients with a lower quality of life in terms of improving quality of life.Conclusions: The results suggest that MBCT might be more beneficial for those with earlier onset and higher levels of rumination and for patients with a lower quality of life. Sophisticated analytical techniques such as QUINT can be used in future research to improve personalized assignment of MBCT to patients. Long-term outcome could also be integrated in this. Show less
Background Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous... Show moreBackground Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients. Methods A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables. Results Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction. Conclusions Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations. Show less
Diermen, L. van; Vanmarcke, S.; Walther, S.; Moens, H.; Veltman, E.; Fransen, E.; ... ; Schrijvers, D. 2019
Psychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the... Show morePsychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the treatment modulates psychomotor disturbance. In 73 adults suffering from major depressive disorder psychomotor functioning was evaluated before, during and after ECT using the observer-rated CORE measure and objective measures including accelerometry and a drawing task. Regression models were fitted to assess the predictive value of melancholic depression (CORE >= 8) and the psychomotor variables on ECT outcome, while effects on psychomotor functioning were evaluated through linear mixed models. Patients with CORE-defined melancholic depression (n = 41) had a 4.9 times greater chance of reaching response than those (n = 24) with non-melancholic depression (Chi-Square = 7.5, P = 0.006). At baseline, both higher total CORE scores (AUC = 0.76; P = 0.001) and needing more cognitive (AUC = 0.78; P = 0.001) and motor time (AUC = 0.76; P = 0.003) on the drawing task corresponded to superior ECT outcomes, as did lower daytime activity levels (AUC = 0.76) although not significantly so after Bonferroni correction for multiple testing. A greater CORE-score reduction in the first week of ECT was associated with higher ECT effectiveness. ECT reduced CORE-assessed psychomotor symptoms and improved activity levels only in those patients showing the severer baseline retardation. Although the sample was relatively small, psychomotor symptoms were clearly associated with beneficial outcome of ECT in patients with major depression, indicating that monitoring psychomotor deficits can help personalise treatment. Show less
Background: Metabolic syndrome (MetS) has been associated with both early- and late-life depression. This study investigated whether baseline MetS and its individual components are associated with... Show moreBackground: Metabolic syndrome (MetS) has been associated with both early- and late-life depression. This study investigated whether baseline MetS and its individual components are associated with the course of depression over six years among older persons with a formal depression diagnosis.Methods: Data were used from 378 older persons with a depressive disorder from the Netherlands Study of Depression in Old age (NESDO) with a 6-year follow-up. A formal depression diagnosis according to DSM-IV-TR criteria was ascertained with the Composite International Diagnostic Interview. Severity of depressive symptoms was assessed with the Inventory of Depressive Symptomatology at 6-month intervals. Metabolic syndrome (MetS) was defined according the modified National Cholesterol Education Programme - Adult Treatment Panel III criteria. Primary outcome was time to remission from depression. We applied cox regression analysis for the primary outcome and linear mixed models for secondary analyses.Results: Neither MetS nor its individual components were associated with time to remission from depression (MetS: HR = 1.03; 95% CI = 0.74 - 1.44; p = 0.85), or with depression severity (MetS: B = 0.02; SE = 0.04; p = 0.64) and course of depressive symptoms (MetS: B = -0.01; SE = 0.01; p = 0.23) over 6-years follow-up.Limitations: Attrition was relatively high (46.8%). Furthermore, we only had information on formal depression diagnosis at baseline, 2-year, and 6-year follow-up.Conclusions: We found no evidence for an effect of baseline presence of metabolic dysregulation on the course of formally diagnosed depression in older persons. Metabolic syndrome in depressed patients should be clinically monitored for other reasons than predicting chronicity or severity of depression. Show less
