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
Ter Avest, M.J.; Dusseldorp, E.; Huijbers, M.J.; Van Aalderen, J.R.; Cladder-Micus, M.B.; Spinhoven, P.; ... ; Speckens, A.E.M. 2019
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
This dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from... Show moreThis dissertation contains the results of an RCT into the effectiveness of an online self-help intervention for people living with HIV (PLWH) and depressive symptoms. Many PLWH suffer from depressive symptoms. Online interventions to treat depression may have benefits, such as less perceived stigma, a large reach and high accessibility. The online self-help intervention that we investigated is based on cognitive behavioral therapy and contains 4 components: stimulating activities, relaxation exercises, changing negative thoughts and goal attainment. Two meta-analyses were conducted and the results point to the effectiveness of psychosocial interventions for PLWH to improve depressive symptoms, anxiety symptoms, quality of life, psychological well-being, and medication adherence. The most important result of the RCT was that the intervention together with telephone coaching is effective in reducing depressive symptoms, compared to an attention-only control group. It was also found that the intervention may be effective for all PLWH, regardless of certain baseline characteristics. Furthermore, behavioral activation and goal reengagement were found to be mediators of the intervention effect. Also, the intervention is likely to be cost-effective compared to attention only. As eHealth interventions have benefits compared to face-to-face interventions, they should be more widely implemented in the mental healthcare for PLWH. 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
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 FST 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
Kunst, L.E.; Groot, J. de; Does, A.J.W. van der 2019
The gender difference in the prevalence of depression is well-documented, poorly understood and multifactorial. Considering that gender differences exist in the expression of emotions, we... Show moreThe gender difference in the prevalence of depression is well-documented, poorly understood and multifactorial. Considering that gender differences exist in the expression of emotions, we hypothesized that ambivalence over the expression of sadness and anger contributes to the difference in depression scores between men and women. Questionnaires on depressive symptoms and ambivalence regarding sadness and anger expression were completed by 550 respondents (66.9% women, average age 27.8years). Women reported more depressive symptoms and were more ambivalent over the expression of both sadness and anger than men. Ambivalence over sadness andto a lesser extentanger mediated the relationship between gender and depressive symptoms. We conclude that ambivalence over emotion expression may partly explain why depression occurs more frequently in women than men. Show less
The main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction... Show moreThe main aim of this thesis is to explore risk factors associated to an increased risk of adverse outcomes for heart failure (HF) patients and improve the early re-admission or mortality prediction in HF. Data from two studies (OPERA-HF study in the UK and SAPHIRE study in US) has been used to explore a wide range of variables as potential risk factors. We found that depression is a significant and independent predictor of all-cause mortality among HF patients. Depression was also significantly associated with recurrent events: unplanned readmission or mortality. Other psychosocial or non-clinical variables independently associated with increasing risk of recurrent events in the year following discharge after a HF hospital admission were: presence of frailty, moderate-to-severe anxiety, living alone and the presence of cognitive impairment. We then used data from the OPERA-HF study to develop a 30-day composite outcome model and to explore the added predictive value of non-clinical predictors to early outcomes: 30-day unplanned readmission or mortality. The performance of the model improved by including physical frailty and social support next to clinical variables. The transportability of the model to a different geography was proved in the external validation of the model on the SAPHIRE study data. Show less
