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
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
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
Background: Patients with various psychiatric disorders may suffer from feelings of anger, sometimes leading to maladaptive (e.g., aggressive) behaviors. We examined to what extent depressive and... Show moreBackground: Patients with various psychiatric disorders may suffer from feelings of anger, sometimes leading to maladaptive (e.g., aggressive) behaviors. We examined to what extent depressive and anxiety disorders, relevant clinical correlates, and sociodemographics determined the level of trait anger and the prevalence of recent anger attacks.Methods: In the Netherlands Study of Depression and Anxiety (NESDA), the Spielberger Trait Anger Subscale and the Anger Attacks Questionnaire were analyzed in patients with depressive (n = 204), anxiety (n = 288), comorbid (n = 222), and remitted disorders (n = 1,107), as well as in healthy controls (n = 470) based on DSM-IV criteria.Results: On average, participants were 46.2 years old (SD = 13.1) and 66.3% were female. Trait anger and anger attacks were most prevalent in the comorbid group (M = 18.5, SD = 5.9, and prevalence 22.1%), followed by anxiety disorder, depressive disorder, remitted disorder, and controls (M = 12.7; SD = 2.9, and prevalence 1.3%). Major depressive disorder, social phobia, panic disorder, and generalized anxiety disorder were most strongly associated to trait anger and anger attacks.Limitations: Due to a cross-sectional design, it was not possible to provide evidence for temporal or causal relationships between anger and depressive and anxiety disorders.Conclusions: Trait anger and anger attacks are linked to depressive and anxiety disorders, although the strength of the relationship differed among both anger constructs. Show less
Ter Avest, M.J.; Dusseldorp, E.; Huijbers, M.J.; Van Aalderen, J.R.; Cladder-Micus, M.B.; Spinhoven, P.; ... ; Speckens, A.E.M. 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
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
Background and objectives: Comorbidity among anxiety and depression disorders and their symptoms is high. Rumination and worry have been found to mediate prospective cross-disorder relations... Show moreBackground and objectives: Comorbidity among anxiety and depression disorders and their symptoms is high. Rumination and worry have been found to mediate prospective cross-disorder relations between anxiety and depression disorders and their symptoms in adolescents and adults. We examined whether generic repetitive negative thinking (RNT), that is content- and disorder-independent, also mediates prospective cross-disorder associations between anxiety and depressions disorders and their symptoms.Methods: This was studied using a 5-year prospective cohort study. In a mixed sample of 1859 adults (persons with a prior history of or a current affective disorder and healthy individuals), we assessed DSM-IV affective disorders (Composite Interview Diagnostic Instrument), anxiety (Beck Anxiety Inventory) and depression symptoms (Inventory of Depressive Symptomatology) and RNT (Perseverative Thinking Questionnaire).Results: We found that baseline depression disorders and symptom severity have predictive value for anxiety disorders and symptom severity five years later (and vice versa) and that these associations were significantly mediated by level of RNT as assessed two years after baseline. The significant and rather large mediation effects seemed mainly due to the mental capacity captured by RNT, especially in the prospective relation of anxiety with future depression.Limitations: The mediation effects were greatly attenuated or even nullified after rigorously controlling for concomitant psychopathology at two years after baseline.Conclusions: From these results it can be concluded that repetitive negative thinking could be an important transdiagnostic factor, that may constitute a suitable target for treatment. Show less
The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent's acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as 'depressed'. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the EST is still increasing and that the majority of researchers qualifies the rodent's floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
