Didi Rhebergen

• Vrije Universiteit Amsterdam

Introduction Cognitive side effects, such as memory loss, associated with electroconvulsive therapy (ECT) have been extensively studied. However, knowledge about (sub)acute confusional states during ECT is limited, particularly in older adults with depression. Their incidence, recurrence, and co‐occurrence remain unclear. This study aimed to descri...

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwa...

Objectives: Despite expanding knowledge about the internal and external resources that contribute to resilience among individuals who have experienced depression, the long-term accessibility and protectiveness of these resources across different stressors is unknown. We investigated whether and how the resilience resources of individuals who previ...

Objectives Late Life Depression (LLD) is associated with increased mortality rates, but it remains unclear which depressed patients are at increased risk. This study examined the mortality risk of previously identified subgroups of depressed older patients based on age‐related clinical features (the presence of physical and cognitive frailty). Met...

Older adults who have had a major depressive disorder (MDD) have a high risk of relapse. Although risk factors for depression have been researched extensively, less is known about protective factors, and what experiences might strengthen subsequent resilience and help to prevent relapse. Therefore, this qualitative study explored factors of resilie...

Objectives: Personality traits and affective disorders are both related to functional limitations. It is unknown whether personality traits have an additional effect on functioning in older adults with affective disorders. We studied the association between personality traits and functioning within this group. Methods: We performed a cross-secti...

Background: Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both struct...

Objective: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). Methods: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change,...

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depressive disorders. A recent multi-center study found no consistent changes in correlation-based (undirected) resting-state connectivity after ECT. Effective (directed) connectivity may provide more insight into the working mechanism of ECT. Objective...

Background Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7–36% of patients and recur in 19–54% of patients. PIA has the potential to cause dangerous situations for the patient and staff members aside from the financial impact. To date, it is unclear which pharmacological interven...

Background: Severe depression is associated with accelerated brain aging. BrainAge gap, the difference between predicted and observed BrainAge was investigated in patients with late-life depression (LLD). We aimed to examine BrainAge gap in LLD and its associations with clinical characteristics indexing LLD chronicity, current severity, prior to e...

Background: Traditional cardiovascular risk indicators only partially explain cardiovascular risks in depressed persons. Depressed persons may exhibit a profile of cardiovascular risk indicators that goes beyond traditional cardiovascular risk indicators, such as symptom severity, insomnia, loneliness and neuroticism, yet research on the added val...

Objectives Determinants of frailty are generally explored within context of somatic healthcare and/or lifestyle characteristics. To examine the impact of personality traits on change in frailty and the potential role of depression. Methods A 2-year follow-up study including 285 patients with a depressive disorder and 116 never-depressed controls....

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and...

Objective While research found heterogeneous changes in mental health during the COVID-19 pandemic, less is known about the long term changes in mental health in psychiatric groups. Therefore, we applied a data-driven method to detect sub-groups with distinct trajectories across two years into the pandemic in psychiatric groups, and described their...

Introduction Both older age bipolar disorder (OABD) and late life depression (LLD) have been associated with cognitive dysfunction. It is unclear how cognitive functioning differs between these disorders and what the influence of current depressive symptoms is. Methods We compared OABD (n = 148), LLD (n = 378) and healthy controls (HC) (n = 132) o...

Background Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. Aims We aim to investigate potential predictors of the differences in changes in mental health. Method Data were aggregated from three Dutch ongoing prospective cohorts with simi...

Objective: Electroconvulsive therapy (ECT) is a safe and effective treatment, especially in psychotic late-life depression (LLD). However, it is not yet clear whether the greater efficacy seen in psychotic LLD is because of a shorter index episode duration. The first aim of this study was to substantiate the superior ECT remission rates in patients...

Purpose Subjective quality of life (SQOL) is increasingly valued as an important outcome in schizophrenia treatment. The current study aims to gain insight into changes in SQOL during 5-year follow-up in older persons with schizophrenia spectrum disorders (SSD). Methods The sample consisted of a catchment area-based group of 75 older Dutch patient...

Background Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confu...

Background Child abuse is a major global burden with an enduring negative impact on mental and physical health. A history of child abuse is consistently associated with worse cognitive performance among adults; data in older age groups are inconclusive. Since affective symptoms and cognitive functioning are interrelated among older persons, a syner...

This chapter discusses the specific factors that play a role in depression in older people, including the large heterogeneity of the concept, its clinical presentations, diagnostic procedures and identification of risk factors, consequences, and treatment of depression in late life. However, compared to the Diagnostic and Statistical Manual (DSM),...

Background Little is known about the longer-term impact of the Covid-19 pandemic beyond the first months of 2020, particularly for people with pre-existing mental health disorders. Studies including pre-pandemic data from large psychiatric cohorts are scarce. Methods Between April 2020 and February 2021, twelve successive online questionnaires wer...

Background/Objectives – Frailty is highly prevalent with increasing age. Based on the concept of depression as a disorder of accelerated ageing and its association with inflammation and metabolic dysregulation, we examined whether frailty measures at baseline and over time differed between immuno-metabolic subtypes of late-life depression. Methods...

Background Electroconvulsive therapy (ECT) is the most effective treatment for severe late-life depression (LLD), and several hypotheses on the precise working mechanism have been proposed. Preclinical evidence suggests that ECT induces changes in neurotrophin and inflammatory signaling and that these neurotrophic and inflammatory systems affect ea...

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive ther...

Background Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDE). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential but associations with treatment response in psychiatry are seld...

Objective: Should we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with de...

Outcome of schizophrenia in later life can be evaluated from different perspectives. The recovery concept has moved forward this evaluation, discerning clinical-based and patient-based definitions. Longitudinal data on measures of recovery in older individuals with schizophrenia are scant. This study evaluated the five-year outcome of clinical reco...

Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior...

Background Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structu...

An influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepr...

Objective To determine if there is a synergistic effect between clinically relevant depressive symptoms and cardiovascular risk factors that disproportionately increases the risk of cardiovascular disease (CVD) among older adults with depressive symptoms. Methods Data were obtained from the Longitudinal Aging Study Amsterdam, a longitudinal cohort...

Objectives Discordance between self-reported functional limitations and performance-based physical functioning may have a negative impact in functional independence in older adults. We longitudinally examined baseline apathy- and depressive symptomatology as associates of discordance. Method 469 participants from the multi-site cohort study NESDO...

Introduction Depressive disorder has been conceptualised as a condition of accelerated biological ageing. We operationalized a frailty index (FI) as marker for biological ageing aimed to explore the bidirectional, longitudinal association between frailty and either depressive symptoms or depressive disorder. Methods – A cohort study with 6-year fo...

Objectives An association is found between changes in cytokine levels and antidepressant treatment outcome. Also, a proinflammatory profile is associated with a favourable electroconvulsive therapy (ECT) outcome. This paper investigates the pattern of inflammatory markers during a course of ECT in older depressed patients and whether this pattern i...

Introduction Aging is characterized by a deterioration of health, which often manifests in multiple health domains. Depressive symptoms, cardiovascular morbidity and loneliness are indicators of mental, physical and social health, respectively, and are highly prevalent at old age. The aim of this study was to investigate how these indicators mutual...

Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase...

Objectives Depression both affects physical activity (PA) and cognition in older persons, yet its impact on the association between PA and cognitive decline is to be determined. We aimed to investigate the association between baseline PA and cognitive functioning over time, stratified for depression. Methods We used data of the Netherlands Study o...

Background Unidirectional studies suggest that the effects between cardiovascular disease, depressive symptoms and loneliness are reciprocal, but this has not been tested empirically. The aim was to study how cardiovascular morbidity, depressive symptoms and loneliness influence each other longitudinally. Methods Data from 2979 older adults from t...

Objectives – While vitamin D is involved in frailty as well as depression, hardly any study has examined the course of vitamin D levels prospectively. The objective of this study is to examine whether a change of vitamin D in depressed older adults is associated with either depression course, course of frailty, or both. Methods – The study populati...

In this commentary, we address current clinical practice of long-term antidepressant use in older adults with depression, and recommend improvements. Compared with younger adults, older adults more frequently use antidepressants in the long term, although they may not always benefit from them, and in spite of an increased risk for adverse events. U...

Introduction Depressive symptoms are highly prevalent and clinically relevant in schizophrenia spectrum disorder (SSD) patients. So far, little is known about to what extent the depressive symptom profile in SSD is comparable to that seen in major depressive disorder (MDD). Methods Data were derived from the Genetic Risk and Outcome of Psychosis s...

Background Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LDD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function d...

Background The impact of the COVID-19 pandemic on mental health in people with pre-existing mental health disorders is unclear. In three psychiatry case-control cohorts, we compared the perceived mental health impact and coping and changes in depressive symptoms, anxiety, worry, and loneliness before and during the COVID-19 pandemic between people...

Background Loneliness and social isolation have both been found to be associated with increased mortality in previous studies. One potential underlying mechanism is via the hypothalamic-pituitary-adrenal axis. Objective This study aimed to examine the association between social network size and cortisol, to analyze the associations between both lo...

Objective: The objective of this study was to examine correlates of discordance between 13-year trajectories of self-reported functional limitations and performance-based physical functioning in older adults. Method: We included 2,135 participants from the population-based Longitudinal Aging Study Amsterdam, the Netherlands, followed across 1995-20...

Background The prevalence of loneliness increases with age. The presence of loneliness in older adults has been found to be associated with health problems such as depression, decreased cognitive functioning, increases in systolic blood pressure and increased mortality. The underlying mechanisms of the higher mortality risk are largely unknown. Me...

Background A substantial number of patients with late-life depression (LLD) that remitted after ECT experience relapse. Identifying risk factors for relapse may guide clinical management to devote attention to those at increased risk. Therefore the current study aims to evaluate which baseline clinical characteristics are related to relapse within...

The nature of schizophrenia spectrum disorders with an onset in middle or late adulthood remains controversial. The aim of our study was to determine in patients aged 60 and older if clinically relevant subtypes based on age at onset can be distinguished, using admixture analysis, a data-driven technique. We conducted a cross-sectional study in 94...

Background With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance and physical frailty. Methods A clinical cohort study of 375 depressed older p...

Background The heterogeneity of late-life depression hampers diagnosis and treatment. Data-driven methods have identified several subtypes of depression in older persons, but the longitudinal stability of these subtypes remains unknown. Methods In total 111 older persons with a major depressive disorder both at baseline and 2-year follow-up from...

Objective Clinical characteristics appear limited in their ability to predict course of anxiety disorders, therefore we explored the predictive value of biological parameters on course of anxiety disorders. Methods 907 persons with an anxiety (panic, social phobia, generalised anxiety) disorder with a baseline and two-year follow-up measure were s...

Objective Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate th...

Background Symptoms of apathy are common in older persons. Negative effects on physical performance and fall risk are plausible, considering the pathophysiology of apathy. However, literature is scarce. Aim To longitudinally assess the association between apathy and 1) decline of physical performance and 2) the number of falls in older community-d...

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number o...

Objective: Depression has been associated with increased mortality rates, and modifying mechanisms have not yet been elucidated. We examined whether specific subtypes or characteristics of late-life depression predict mortality. Methods: A cohort study including 378 depressed older patients according to DSM-IV criteria and 132 never depressed compa...

Autism and depression often co-occur. Through network analysis, we seek to gain a better understanding of this co-occurrence by investigating whether (1) autism and depression share overlapping groups of symptoms and/or (2) are connected through a bridge of mastery or worry symptoms. This is addressed in two complimentary studies: (1) Study 1 focus...

Background Symptoms of apathy are common in older persons. Negative effects on physical performance and fall risk are plausible, considering the pathophysiology of apathy. However, literature is scarce. Aim To longitudinally assess the association between apathy and (1) decline of physical performance and (2) the number of falls in older community...

Background: In mental health research, functional recovery is increasingly valued as an important outcome in addition to symptomatic remission. Methods: Course types of functional limitations among depressed older patients and its relation with symptomatic remission were explored in a naturalistic cohort study (Netherlands Study of Depression in...

Background: Increasing evidence suggests that glial mediated disruption of neuroplasticity contributes to depression. S100 calcium-binding protein B (S100B) promotes neuronal protection in nanomolar concentrations. Studies on its possible role as a treatment outcome marker in affective disorders are limited. Recent evidence suggests a putative rol...

Background Major depressive disorder (MDD) represents a leading cause of disability. This study examines the course of disability in patients with chronic, recurrent and remitting MDD compared to healthy controls and identifies predictors of disability in remitting MDD. Methods We included 914 participants from the Netherlands Study of Depression...

Background: Compelling evidence links elevated levels of C-reactive protein (CRP) and other inflammatory markers to poor treatment outcome of antidepressant medication. Little is known about the contribution of low-grade inflammation to treatment response to electroconvulsive therapy (ECT) in severely depressed patients. Method: Associations bet...

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 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...

While brain-derived neurotrophic factor (BDNF) has been shown to predict response to pharmacotherapy in depression, studies in electroconvulsive therapy (ECT) are small and report conflicting results. This study assesses the association between pre-treatment BDNF levels and ECT outcome in severe late-life unipolar depression (LLD). The potential of...

Background: The association between pain and dementia is complicated and may depend on underlying brain pathology. It was hypothesized that both medial temporal atrophy (MTA) and global cortical atrophy (GCA) predicted no/mild pain, while white matter hyperintensities (WMH) predicted moderate/severe pain. Objectives: To study the association betwee...

Objectives In clinical practice, particularly melancholic depression benefits from electroconvulsive therapy (ECT), albeit research melancholia criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) is not conclusive. We compared clinical characteristics and ECT outcome of melancholic and nonmelancholic depression, here defin...

Background Severe depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-pati...

Although highly prevalent, motor syndromes in psychiatry and motor side effects of psychopharmacologic agents remain understudied. Catatonia is a syndrome with specific motor abnormalities that can be seen in the context of a variety of psychiatric and somatic conditions. The neuroleptic malignant syndrome is a lethal variant, induced by antipsycho...

Objectives To establish the course of metabolic syndrome (MS) rates in older patients with severe mental illness (SMI) after five‐year follow‐up and evaluate whether MS at baseline is associated with mortality or diabetes at follow‐up. Methods Patients (>60 years of age) with SMI (N=100) were included at a specialized mental health outpatient clin...

Apathy, a common and disabling behavioural syndrome in older persons, has been associated with impaired physical performance and executive dysfunction. Both are fall risk factors and they share pathophysiological pathway. We cross-sectionally examined the association between apathy and recurrent falling (≥2 falls in the past 12 months) and number o...

Controversy exists concerning the reliability of retrospective self-reports on childhood abuse since this method might be subject to under- or overreporting. Until now, no studies have been done in older adults, although reasons for under- or overreporting could be even more prominent in this age group. In this first study in older adults, test-ret...

Objectives Apathy, a lack of motivation, is frequently seen in older individuals, with and without depression, with substantial impact on quality of life. This prospective cohort study of patients with severe late‐life depression treated with electroconvulsive therapy (ECT) aims to study the course of apathy and the predictive value of vascular bur...

Introduction: Electroconvulsive therapy (ECT) is an important and effective treatment for depression. However, research on course trajectories of depressive symptoms during ECT is limited. Insight into putative differences in speed of response of depressive symptom dimensions may enable clinicians to optimally inform patients and their relatives....

Background Currently, the predictive value of psychiatric diagnosis is inadequate compared to other medical fields. It has been suggested that the use of a network model might aid in acquiring new insights into the underlying connections between symptoms (Bringmann et al., 2013). In addition, previous research (Bakker et al., 2012) has revealed ass...

Background In older people, both apathy and depression (which frequently co-occurs with apathy) have been associated with poor physical functioning, a major health concern. We investigated the association between apathy and physical functioning in older people without dementia and whether this association is modified by depression. Methods We used...

Background: There is growing evidence that inflammatory and cortisol dysregulation are underlying pathophysiological mechanisms in the aetiology of major depressive disorder, particularly in younger adults. However, findings of biological disturbances in late-life depression have been divergent, probably due to the even greater heterogeneity of de...

Objectives: Electroconvulsive therapy (ECT) is the most effective treatment for depression, however consensus on predictors for ECT-outcome is lacking. We aim to examine the relation between pre-ECT salivary cortisol values and clinical characteristics and ECT-outcome in depressed, older persons. Methods: 102 inpatients meeting DSM-IV-criteria for...

Objective: Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psych...

Inconsistent results are found in the involvement of the Hypothalamus-Pituitary-Adrenal (HPA)-axis in cognitive functioning. This study examined the association between various saliva cortisol measures (the 1-h awakening cortisol, evening cortisol, diurnal change, and cortisol suppression) and cognitive functioning (episodic memory, processing spee...

Background The behavioral variant of frontotemporal dementia (bvFTD) has a broad differential diagnosis including other neurological and psychiatric disorders. Psychiatric misdiagnoses occur in up to 50% of bvFTD patients. Numbers on misdiagnosis of bvFTD in psychiatric disorders are lacking. Objective The aim of our study was to investigate the f...

Objective: To assess the pain prevalence, pain intensity, and pain medication use in older patients with a diagnosed subtype of dementia, mild cognitive impairment (MCI), or subjective cognitive impairment (SCI). Design: Cross-sectional. Setting: Outpatient memory clinics. Subjects: In total, 759 patients with Alzheimer's disease (AD), vascu...

Background Late-life depression is thought to differ in clinical presentation from early-life depression. Particularly, late-life depression is considered to be more characterized by apathy than is early-life depression. Lacking convincing evidence, this study examines the presence and associated socio-demographic/clinical characteristics of apathy...

Age-of-onset has been found to be a marker of clinical relevant subtypes in various medical and psychiatric disorders. In addition, clinical importance of age-of-onset has been reported in Generalized Anxiety Disorder (GAD) but in research to date, arbitrary cut-off ages have been used. In this study, admixture analysis was used to determine the be...

Background: Clinical findings indicate heterogeneity of depressive disorders, stressing the importance of subtyping depression for research and clinical care. Subtypes of the common late life depression are however seldom studied. Data-driven methods may help provide a more empirically-based classification of late-life depression. Methods: Data...