BACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized examination of motor... Show moreBACKGROUND: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized examination of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown.METHODS: We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by 1) constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders and of intelligence and 2) testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n = 5160) of patients with HD.RESULTS: Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence.CONCLUSIONS: Polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD. Show less
Munter, L. de; Polinder, S.; Haagsma, J.A.; Kruithof, N.; Ree, C.L.P. van de; Steyerberg, E.W.; Jongh, M. de 2020
Objective: To describe the prevalence and prognostic factors of symptoms of anxiety and depression and posttraumatic stress symptoms (PTSS) after injury in the clinical trauma population.Design:... Show moreObjective: To describe the prevalence and prognostic factors of symptoms of anxiety and depression and posttraumatic stress symptoms (PTSS) after injury in the clinical trauma population.Design: Multicenter, prospective, observational cohort study.Setting: Ten hospitals in Noord-Brabant, The Netherlands.Participants: Four thousand two hundred thirty-nine adult patients (N=4239) admitted due to injury between August 2015 and December 2016.Interventions: Patients were asked to complete a questionnaire at 1 week and at 1, 3, 6, and 12 months after injury.Main Outcome Measures: The Hospital Anxiety and Depression Scale was used to assess anxiety and depressive symptoms and the Impact of Event Scale was used to assess PTSS.Results: The prevalence of symptoms of anxiety and depression decreased from 10% and 12%, respectively, at 1 week after injury to 7% and 7% at 12 months after injury. Acute traumatic stress symptoms were present in 13% at 1 week and PTSS was prevalent in 10% of the participants at 12 months after injury. Strong prognostic factors for poor psychological outcome in multivariable logistic mixed models were preinjury frailty, psychological complaints and nonworking status preinjury, female sex, low educational level, and accident category (ie, traffic accident, work-related accident, or accidents at home compared to sport injuries).Conclusions: Psychological distress is a common health problem during the first year after injury. Important prognostic factors for psychological distress include psychological complaints before injury and frailty. Early recognition of psychological problems after injury could facilitate discussion between caregivers and patients and improve recovery. (C) 2019 by the American Congress of Rehabilitation Medicine Show less
Gibson-Smith, D.; Bot, M.; Brouwer, I.A.; Visser, M.; Giltay, E.J.; Penninx, B.W.J.H. 2020
Purpose Adherence to the Mediterranean diet has been associated with fewer depressive symptoms, however, it is unknown whether this is attributed to some or to all components. We examined the... Show morePurpose Adherence to the Mediterranean diet has been associated with fewer depressive symptoms, however, it is unknown whether this is attributed to some or to all components. We examined the association between the individual food groups of the Mediterranean Diet Score (MDS), in isolation and in combination, with depression and anxiety (symptom severity and diagnosis). Methods Data from 1634 adults were available from the Netherlands Study of Depression and Anxiety. Eleven energy-adjusted food groups were created from a 238-item food frequency questionnaire. In regression analysis, these were associated in isolation and combination with (1) depressive and anxiety disorders (established with the Composite International Diagnostic Interview) (current disorder n = 414), and (2) depression and anxiety severity [measured with the Inventory of Depressive Symptomatology (IDS), the Beck Anxiety Inventory (BAI) and the Fear Questionnaire (FEAR)]. Results Overall, the MDS score shows the strongest relationships with depression/anxiety [Diagnosis: odds ratio (OR) 0.77 per SD, 95% confidence interval (95% CI) 0.66-0.90, IDS: standardised betas (beta) - 0.13, 95% CI - 0.18, - 0.08] and anxiety (BAI: beta - 0.11, 95% CI - 0.16, - 0.06, FEAR: beta - 0.08, 95% CI - 0.13, - 0.03). Greater consumption of non-refined grains and vegetables was associated with lower depression and anxiety severity, whilst being a non-drinker was associated with higher symptom severity. Higher fruit and vegetable intake was associated with lower fear severity. Non-refined grain consumption was associated with lower odds and being a non-drinker with greater odds of current depression/anxiety disorders compared to healthy controls, these associations persisted after adjustment for other food groups (OR 0.82 per SD, 95% CI 0.71-0.96, OR 1.26 per SD 95% CI 1.08-1.46). Conclusion We can conclude that non-refined grains, vegetables and alcohol intake appeared to be the driving variables for the associated the total MDS score and depression/anxiety. However, the combined effect of the whole diet remains important for mental health. It should be explored whether an increase consumption of non-refined grains and vegetables may help to prevent or reduce depression and anxiety. Show less
BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was... Show moreBACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons.METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses.RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein Al were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms.CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity. Show less
The ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve... Show moreThe ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve the mesocortical circuitry. Coping with stress increases VTA-DA excitability, but when the stressor becomes chronic the VTA-DA circuit is less active, which may lead to degeneration and local microglial activation. This switch between activation and inhibition of VTA-DA neurons is modulated by e.g. corticotropin-releasing hormone (CRH), opioids, brain-derived neurotrophic factor (BDNF), and the adrenal glucocorticoids. These actions are coordinated with energy-demanding stress-coping styles to promote behavioral adaptation. The VTA circuits show sexual dimorphism that is programmed by sex hormones during perinatal life in a manner that can be affected by glucocorticoid exposure. We conclude that insight in the role of stress in VTA-DA plasticity and connectivity, during reward processing and stress-coping, will be helpful to better understand the mechanism of resilience to breakdown of adaptation. Show less
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
BackgroundResearch in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the... Show moreBackgroundResearch in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents.MethodsWe used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents).ResultsThese analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected.ConclusionsThese analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups. Show less
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
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
Introduction: It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke... Show moreIntroduction: It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up.Patients and methods: In a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0-4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively.Results: Population-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3-4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99-14.25 and 3.04, 95% CI 1.20-7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09-7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers.Conclusions: The results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD. Show less
Many common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to... Show moreMany common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to unraveling the genetic architecture of these polygenetic disorders, a large amount of ‘missing heritability’ remains. A possible explanation is that GWAS, aside single-nucleotide polymorphisms cannot assess the contribution of other important genetic polymorphisms, especially tandem repeats. Tandem repeats constitute 3% of the human genome. Nine hereditary neurodegenerative diseases, known as polyglutamine diseases, including Huntington disease (HD), are the most prevalent disorders associated with tandem repeat variations. These diseases are caused by an elongated cytosine-adenine-guanine (CAG) repeat sequence in the respective polyglutamine disease-associated gene (PDAG). In this dissertation, we provide ample evidence that CAG repeat variations within the ‘normal’ range in PDAGs can affect various aspects of disease, including the age of onset in HD, cognitive function, depression and body mass index. Finally, we found a relatively large prevalence of intermediate and pathological PDAG alleles in the general population. Therefore, we provided support for the role of repetitive DNA polymorphisms in elucidating the ‘missing heritability’ of polygenetic disorders and emphasized the necessity to include these variations in future genetic research. 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