BackgroundAggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA)... Show moreBackgroundAggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA) reduces aggressive incidents.MethodsWe conducted a randomised, triple blind, placebo controlled, single crossover intervention trial. People with intellectual disabilities or borderline intellectual functioning, between 12 and 40 years of age, and showing aggressive behaviour were included. Participants received either a daily dose of dietary supplements, or placebo. Primary outcome was the number of aggressive incidents, measured using the Modified Overt Aggression Scale (MOAS).Resultsthere were 113 participants (placebo, n = 56), of whom 24 (placebo, n = 10) participated in the crossover phase of the trial. All 137 trajectories were included in the analyses. There was no significant difference in mean number of aggressive incidents per day between those assigned to supplements and those who received placebo (rate ratio = 0.93: 95% Confidence Interval [CI] = 0.59–1.45).ConclusionIn this pragmatic trial, we did not find significant differences in the outcomes between the supplement and placebo arms. The COVID-19 pandemic started midway through our trial, this may have affected the results. Show less
Previous studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic... Show morePrevious studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic value of PPT (Dimensional Assessment of Personality Pathology-Short Form) on treatment outcome (Brief Symptom Inventory [BSI-posttreatment]) among patients with depressive and/or anxiety disorders ( N = 5689). Baseline symptom level (BSI-pretreatment) was taken into account as a mediator or moderator variable. Results showed significant effects of PPT on outcome, of which Emotional Dysregulation demonstrated the largest association ( β = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect ( β = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect β = 0.061, p < 0.001) and Inhibition (interaction effect β = 0.062, p < 0.001), but not Compulsivity or Dissocial Behavior, were moderated by the baseline symptom level. PPT predicts higher symptom levels, both before and after treatment, but yields relatively small direct effects on symptom decline when the effect of pretreatment severity is taken into account. Show less
Previous studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic... Show morePrevious studies have failed to take baseline severity into account when assessing the effects of pathological personality traits (PPT) on treatment outcome. This study assessed the prognostic value of PPT (Dimensional Assessment of Personality Pathology-Short Form) on treatment outcome (Brief Symptom Inventory [BSI-posttreatment]) among patients with depressive and/or anxiety disorders (N = 5689). Baseline symptom level (BSI-pretreatment) was taken into account as a mediator or moderator variable. Results showed significant effects of PPT on outcome, of which Emotional Dysregulation demonstrated the largest association (beta = 0.43, p < 0.001). When including baseline BSI score as a mediator variable, a direct effect (beta = 0.11, p < 0.001) remained approximately one-third of the total effect. The effects of Emotional Dysregulation (interaction effect beta = 0.061, p < 0.001) and Inhibition (interaction effect beta = 0.062, p < 0.001), but not Compulsivity or Dissocial Behavior, were moderated by the baseline symptom level. PPT predicts higher symptom levels, both before and after treatment, but yields relatively small direct effects on symptom decline when the effect of pretreatment severity is taken into account. Show less
Objectives: Late-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over... Show moreObjectives: Late-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level. Methods: In the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30-item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged >= 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses. Results: The mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group-level nomothetic approach, four depressive symptom dimensions were identified: "core symptoms", "lethargy/somatic", "sleep", and "appetite/atypical". Items of the "internalizing symptoms" dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms. Conclusions: DTW revealed symptom networks and dimensions based on the within-person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care. Show less
Ottenheim, N.R.; Pan, K.Y.; Kok, A.A.L.; Jorg, F.; Eikelenboom, M.; Horsfall, M.; ... ; Giltay, E.J. 2022
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... Show moreBackground 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 similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006-2016, and who completed online questionnaires at least once during lockdown in The Netherlands between 1 April and 15 May 2020. Sociodemographic, clinical (number of mental health disorders and personality factors) and COVID-19-related variables were analysed as predictors of relative changes in four mental health outcomes (depressive symptoms, anxiety and worry symptoms, and loneliness), using multivariate linear regression analyses. Results We included 1517 participants with (n = 1181) and without (n = 336) mental health disorders. Mean age was 56.1 years (s.d. 13.2), and 64.3% were women. Higher neuroticism predicted increases in all four mental health outcomes, especially for worry (beta = 0.172, P = 0.003). Living alone and female gender predicted increases in depressive symptoms and loneliness (beta = 0.05-0.08), whereas quarantine and strict adherence with COVID-19 restrictions predicted increases in anxiety and worry symptoms (beta = 0.07-0.11).Teleworking predicted a decrease in anxiety symptoms (beta = -0.07) and higher age predicted a decrease in anxiety (beta = -0.08) and worry symptoms (beta = -0.10). Conclusions Our study showed neuroticism as a robust predictor of adverse changes in mental health, and identified additional sociodemographic and COVID-19-related predictors that explain longitudinal variability in mental health during the COVID-19 pandemic. Show less
Background: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role... Show moreBackground: Childhood trauma (CT) is robustly associated with psychiatric disorders including major depressive and anxiety disorders across the life span. The innate immune system may play a role in the relation between CT and stress-related psychopathology. However, whether CT influences the innate production capacity of cytokine levels following ex vivo stimulation by lipopolysaccharide (LPS), is currently unknown. Methods: Using data from the Netherlands Study of Depression and Anxiety (NESDA, n=1237), we examined whether CT (emotional neglect, emotional, physical, and sexual abuse before the age of 16), assessed by the Childhood Trauma Interview, was associated with levels in supernatants of interferon (IFN)gamma, interleukin-2 (IL -2), IL-4, IL-6, IL-8, IL-10, IL-18, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, matrix metalloproteinase-2 (MMP-2), TNF alpha and TNF beta after ex vivo stimulation with LPS. Cytokines were analysed individually and cumulatively (overall inflammation index and number of cytokines in high-risk quartile (HRQ)) using linear regression analyses. Results: After adjustment for demographic, lifestyle, and health-related covariates, total CT severity was asso-ciated with the overall inflammation index (beta = 0.085, PFDR = 0.011), the number of cytokines in HRQ (beta = 0.063, P-FDR = 0.036), and individual markers of IL-2 (beta = 0.067, P-FDR = 0.036), IL-6 (beta = 0.091 PFDR = 0.011), IL-8 (beta = 0.085 P-FDR = 0.011), IL-10 (beta = 0.094 P-FDR = 0.011), MCP-1 (beta = 0.081 P-FDR = 0.011), MIP-1 alpha (beta = 0.061 P-FDR = 0.047), MIP1-beta (beta = 0.077 P-FDR = 0.016), MMP-2 (beta = 0.070 P-FDR = 0.027), and TNF beta (beta = 0.078 PFDR = 0.016). Associations were strongest for individuals with severe CT, reporting multiple types or higher frequencies of trauma. Half of the findings persisted after adjustment for psychiatric status. The findings were consistent across different CT types. Conclusion: Childhood Trauma is associated with increased LPS-stimulated cytokine levels, with evidence for a dose-response relationship. Our results highlight a dysregulated innate immune system capacity in adults with CT, which could contribute to an increased vulnerability for psychopathology and somatic disorders across the lifespan. Show less
Background: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains... Show moreBackground: Childhood trauma (CT) is a risk factor for depressive and anxiety disorders. However, whether CT is more strongly linked to specific clinical features of these disorders remains inconclusive. The current study comprehensively examined cross-sectional and longitudinal associations between CT and depressive/anxiety symptomatology in a large adult sample with current and remitted depressive and/or anxiety disorders. Methods: Baseline (n = 1803), 2-year (n = 1735), 4-year (n = 1585), and 6-year follow-up (n = 1475) data from the Netherlands Study of Depression and Anxiety were used. CT (emotional neglect, emotional/physical/sexual abuse) was assessed at baseline, while depressive/anxiety symptomatology with relevant dimensions (e.g., mood/cognitive, melancholic, general distress, and somatic depression) was assessed at each wave using selfreported questionnaires. Linear regressions and linear mixed models determined cross-sectional and longitudinal associations. Results: Individuals with CT, especially, severe CT, compared to those without CT, had significantly higher scores in overall depressive symptomatology (Cohen's d = 0.674), mood/cognitive depression (d = 0.691), melancholic depression (d = 0.587), general distress (d = 0.561), and somatic depression severity (d = 0.549). Differences were lower, but still highly significant for anxiety (d = 0.418), worry (d = 0.362), and fear/phobic symptomatology (d = 0.359). Effects were consistent across CT types and maintained over six years. Limitations: Retrospectively-reported CT. Conclusions: CT is a risk factor for depressive and anxiety symptomatology across all dimensions and enduring over multiple years. Screening for CT is essential to identify individuals at risk for more severe and chronic manifestations of affective disorders. Show less
Hudson, J.; Cruickshank, M.; Quinton, R.; Aucott, L.; Aceves-Martins, M.; Gillies, K.; ... ; Jayasena, C.N. 2022
Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most... Show moreBackground: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9.5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0.4%] of 1621) than placebo (12 [0.8%] of 1537) without significant differences between groups (odds ratio [OR] 0.46 [ 95% CI 0.17-1.24]; p=0.13). Cardiovascular risk was similar during testosterone treatment (120 [7.5%] of 1601 events) and placebo treatment (110 [7.2%] of 1519 events; OR 1.07 [95% CI 0.81-1.42]; p=0. 62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0.97 [99% CI 0.92- 1.03]; p=0.17), baseline testosterone (interaction 0.97 [0 .82-1.15]; p=0.69), smoking status (interaction 1.68 [0.41-6.88]; p=0.35), or diabetes status (interaction 2.08 [0.89-4.82; p=0.025) were not associated with cardiovascular risk .Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. Show less
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... Show moreBackground: 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 were distributed among participants of the Netherlands Study of Depression and Anxiety, Netherlands Study of Depression in Older Persons, and Netherlands Obsessive Compulsive Disorder Association Study (N = 1714, response rate 62%). Outcomes were depressive symptoms, anxiety, worry, loneliness, perceived mental health impact of the pandemic, fear of Covid-19, positive coping, and happiness. Using linear mixed models we compared trajectories between subgroups with different pre-pandemic chronicity of disorders and healthy controls. Results: Depressive, anxiety and worry symptoms were stable since April-May 2020 whereas happiness slightly decreased. Furthermore, positive coping steadily decreased and loneliness increased - exceeding pre-Covid and April-May 2020 levels. Perceived mental health impact and fear of Covid-19 fluctuated in accordance with national Covid-19 mortality rate changes. Absolute levels of all outcomes were poorer with higher chronicity of disorders, yet trajectories did not differ among subgroups. Limitations: The most vulnerable psychiatric groups may have been underrepresented and results may not be generalizable to lower income countries. Conclusions: After a year, levels of depressive and worry symptoms remained higher than before the pandemic in healthy control groups, yet not in psychiatric groups. Nevertheless, persistent high symptoms in psychiatric groups and increasing loneliness in all groups are specific points of concern for mental health care professionals. Show less
Saito, T.; Does, F.H.S. van der; Nagamine, M.; Wee, N.J. van der; Shigemura, J.; Yamamoto, T.; ... ; Giltay, E.J. 2022
Background First responders to disasters are at risk of developing post-traumatic stress disorder (PTSD). The trajectories of post-traumatic stress symptom severity differ among individuals, even... Show moreBackground First responders to disasters are at risk of developing post-traumatic stress disorder (PTSD). The trajectories of post-traumatic stress symptom severity differ among individuals, even if they are exposed to similar events. These trajectories have not yet been reported in non-Western first responders. Aims We aimed to explore post-traumatic stress symptom severity trajectories and their risk factors in first responders to the 2011 Great East Japan Earthquake (GEJE) - a historically large earthquake that resulted in a tsunami and a nuclear disaster. Method A total of 55 632 Japan Ground Self-Defense Force (JGSDF) personnel dispatched to the GEJE were enrolled in this 7-year longitudinal cohort study. PTSD symptom severity was measured using the Impact of Event Scale-Revised. Trajectories were identified using latent growth mixture models (LGMM). Nine potential risk factors for the symptom severity trajectories were analysed using multinomial logistic regression. Results Five symptom severity trajectories were identified: 'resilient' (54.8%), 'recovery' (24.6%), 'incomplete recovery' (10.7%), 'late-onset' (5.7%), and 'chronic' (4.3%). The main risk factors for the four non-resilient trajectories were older age, personal disaster experiences and working conditions. These working conditions included duties involving body recovery or radiation exposure risk, longer deployment length, later or no post-deployment leave and longer post-deployment overtime. Conclusions The majority of first responders to GEJE were resilient and developed few or no PTSD symptoms. A substantial minority experienced late-onset and chronic symptom severity trajectories. The identified risk factors can inform policies for prevention, early detection and intervention in individuals at risk of developing symptomatic trajectories. Show less
Background Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in... Show moreBackground Aggression and violent incidents are a major concern in psychiatric in-patient care. Nutritional supplementation has been found to reduce aggressive incidents and rule violations in forensic populations and children with behavioural problems. Aims To assess whether multivitamin, mineral and n-3 polyunsaturated fatty acid supplementation would reduce the number of aggressive incidents among long-stay psychiatric in-patients. Method The trial was a pragmatic, multicentre, randomised, double-blind placebo-controlled study. Data were collected from 25 July 2016 to 29 October 2019, at eight local sites for mental healthcare in The Netherlands and Belgium. Participants were randomised (1:1) to receive 6-month treatment with either three supplements containing multivitamins, minerals and n-3 polyunsaturated fatty acid, or placebo. The primary outcome was the number of aggressive incidents, determined by the Staff Observation Aggression Scale - Revised (SOAS-R). Secondary outcomes were patient quality of life, affective symptoms and adverse events. Results In total, 176 participants were randomised (supplements, n = 87; placebo, n = 89). Participants were on average 49.3 years old (s.d. 14.5) and 64.2% were male. Most patients had a psychotic disorder (60.8%). The primary outcome of SOAS-R incidents was similar in supplement (1.03 incidents per month, 95% CI 0.74-1.37) and placebo groups (0.90 incidents per month, 95% CI 0.65-1.19), with a rate ratio of 1.08 (95% CI 0.67-1.74, P = 0.75). Differential effects were not found in sensitivity analyses on the SOAS-R or on secondary outcomes. Conclusions Six months of nutritional supplementation did not reduce aggressive incidents among long-stay psychiatric in-patients. Show less
Background: Setting up and conducting a randomised controlled trial (RCT) has many challenges-particularly trials that include vulnerable individuals with behavioural problems or who reside in... Show moreBackground: Setting up and conducting a randomised controlled trial (RCT) has many challenges-particularly trials that include vulnerable individuals with behavioural problems or who reside in facilities that focus on care as opposed to research. These populations are underrepresented in RCTs. Approach: In our paper, we describe the challenges and practical lessons learned from two RCTs in two care settings involving long-stay psychiatric inpatients and people with intellectual disabilities. We describe five main difficulties and how these were overcome: (1) multisite setting, (2) inclusion of vulnerable participants, (3) nutritional supplements and placebos, (4) assessment of behavioural outcomes, and (5) collecting bio samples. Conclusions: By sharing these practical experiences, we hope to inform other researchers how to optimally design their trials, while avoiding and minimising the difficulties that we encountered, and to facilitate the implementation of a trial. Both trials were registered in the Clinical Trials Register (RCT A: NCT02498106; RCT B: NCT03212092). Show less
Bokma, W.A.; Zhutovsky, P.; Giltay, E.J.; Schoevers, R.A.; Penninx, B.W.J.H.; Balkom, A.L.J.M. van; ... ; Wingen, G.A. van 2022
Background Disease trajectories of patients with anxiety disorders are highly diverse and approximately 60% remain chronically ill. The ability to predict disease course in individual patients... Show moreBackground Disease trajectories of patients with anxiety disorders are highly diverse and approximately 60% remain chronically ill. The ability to predict disease course in individual patients would enable personalized management of these patients. This study aimed to predict recovery from anxiety disorders within 2 years applying a machine learning approach. Methods In total, 887 patients with anxiety disorders (panic disorder, generalized anxiety disorder, agoraphobia, or social phobia) were selected from a naturalistic cohort study. A wide array of baseline predictors (N = 569) from five domains (clinical, psychological, sociodemographic, biological, lifestyle) were used to predict recovery from anxiety disorders and recovery from all common mental disorders (CMDs: anxiety disorders, major depressive disorder, dysthymia, or alcohol dependency) at 2-year follow-up using random forest classifiers (RFCs). Results At follow-up, 484 patients (54.6%) had recovered from anxiety disorders. RFCs achieved a cross-validated area-under-the-receiving-operator-characteristic-curve (AUC) of 0.67 when using the combination of all predictor domains (sensitivity: 62.0%, specificity 62.8%) for predicting recovery from anxiety disorders. Classification of recovery from CMDs yielded an AUC of 0.70 (sensitivity: 64.6%, specificity: 62.3%) when using all domains. In both cases, the clinical domain alone provided comparable performances. Feature analysis showed that prediction of recovery from anxiety disorders was primarily driven by anxiety features, whereas recovery from CMDs was primarily driven by depression features. Conclusions The current study showed moderate performance in predicting recovery from anxiety disorders over a 2-year follow-up for individual patients and indicates that anxiety features are most indicative for anxiety improvement and depression features for improvement in general. 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
OBJECTIVE: Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome or premenstrual dysphoric disorder also seeking contraception, but evidence for... Show moreOBJECTIVE: Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome or premenstrual dysphoric disorder also seeking contraception, but evidence for this treatment is scarce. We aimed to determine (1) the level of evidence for the efficacy of combined oral contraceptives in managing premenstrual depressive symptoms and overall premenstrual symptomatology and (2) the comparative efficacy of combined oral contraceptives (the International Prospective Register of Systematic Reviews registration number CRD42020205510). DATA SOURCES: We searched Cochrane Central Register of Controlled Trials, PubMed, Web of Science, PsycINFO, EMCare, and Embase from inception to June 3, 2021. STUDY ELIGIBILITY CRITERIA: All randomized clinical trials that evaluated the efficacy of combined oral contraceptives in women with premenstrual syndrome or premenstrual dysphoric disorder were considered eligible for inclusion in this meta-analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A random effect Bayesian pairwise and network meta-analysis was conducted with change in premenstrual depressive symptoms and overall premenstrual symptomatology between baseline and 3 cycles as outcome. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Of 3664 records, 9 eligible trials were included that studied 1205 women with premenstrual syndrome or premenstrual dysphoric disorder (mean age per study range, 24.6-36.5 years). The pairwise meta-analysis revealed that combined oral contraceptives were more efficacious than placebo in treating overall premenstrual symptomatology (standardized mean difference, 0.41; 95% credible interval, 0.17-0.67), but not premenstrual depressive symptoms specifically (standardized mean difference, 0.22; 95% credible interval,-0.06 to 0.47). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology. CONCLUSION: Combined oral contraceptives may improve overall premenstrual symptomatology in women with premenstrual syndrome or premenstrual dysphoric disorder, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other. Show less
Background: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective... Show moreBackground: In longitudinal research, switching between diagnoses should be considered when examining patients with depression and anxiety. We investigated course trajectories of affective disorders over a nine-year period, comparing a categorical approach using diagnoses to a dimensional approach using symptom severity.Method: Patients with a current depressive and/or anxiety disorder at baseline (N = 1701) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Using psychiatric diagnoses, we described 'consistently recovered,' 'intermittently recovered,' 'intermittently recurrent', and 'consistently chronic' at two-, four-, six-, and nine-year follow-up. Additionally, latent class growth analysis (LCGA) using depressive, anxiety, fear, and worry symptom severity scores was used to identify distinct classes.Results: Considering the categorical approach, 8.5% were chronic, 32.9% were intermittently recurrent, 37.6% were intermittently recovered, and 21.0% remained consistently recovered from any affective disorder at nine-year follow-up. In the dimensional approach, 66.6% were chronic, 25.9% showed partial recovery, and 7.6% had recovered.Limitations: 30.6% of patients were lost to follow-up. Diagnoses were rated by the interviewer and questionnaires were completed by the participant.Conclusions: Using diagnoses alone as discrete categories to describe clinical course fails to fully capture the persistence of affective symptoms that were observed when using a dimensional approach. The enduring, fluctuating presence of sub-threshold affective symptoms likely predisposes patients to frequent relapse. The commonness of subthreshold symptoms and their adverse impact on long-term prognoses deserve continuous clinical attention in mental health care as well further research. Show less
A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but... Show moreA cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized betacoefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression. Show less
Background: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for... Show moreBackground: Worldwide, oral contraceptive (OC) use is a very common form of birth control, although it has been associated with symptoms of depression and insomnia. Insomnia is a risk factor for major depressive disorder (MDD) but may also be a symptom of the disorder. Despite the large number of women who use OC, it is yet unknown whether women with previous or current diagnosis of depression are more likely to experience more severe depressive and insomnia symptoms during concurrent OC use than women without diagnosis of depression. Aim: This study examined associations between OC use and concurrent symptoms of depression (including atypical depression) and insomnia as well as between OC and prevalences of concurrent dysthymia and MDD. Participants were adult women with and without a history of MDD or dysthymia. We hypothesized that OC use is associated with concurrent increased severity of depressive symptoms and insomnia symptoms, as well as with an increased prevalence of concurrent diagnoses of dysthymia and MDD. We also hypothesized that a history of MDD or dysthymia moderates the relationship between OC use and depressive and insomnia symptoms. Methods: Measurements from premenopausal adult women from the Netherlands Study of Depression and Anxiety (NESDA) were grouped, based on whether participants were using OC or naturally cycling (NC). OC use, timing and regularity of the menstrual cycle were assessed with a structured interview, self-reported symptoms of depression (including atypical depression), insomnia with validated questionnaires, and MDD and dysthymia with structured diagnostic interviews. Results: We included a total of 1301 measurements in women who reported OC use and 1913 measurements in NC women (mean age 35.6, 49.8% and 28.9% of measurements in women with a previous depression or current depression, respectively). Linear mixed models showed that overall, OC use was neither associated with more severe depressive symptoms (including atypical depressive symptoms), nor with higher prevalence of diagnoses of MDD or dysthymia. However, by disentangling the amalgamated overall effect, within-person estimates indicated increased depressive symptoms and depressive disorder prevalence during OC use, whereas between-person estimated indicated lower depressive symptoms and prevalence of depressive disorders. OC use was consistently associated with more severe concurrent insomnia symptoms, in the overall estimates as well as in the within-person and between-person estimates. Presence of current or previous MDD or dysthymia did not mod-erate the associations between OC use and depressive or insomnia symptoms. Discussion: The study findings showed consistent associations between OC use and more severe insomnia symptoms, but no consistent associations between OC and depressive symptoms or diagnoses. Instead, post-hoc analyses showed that associations between OC and depression differed between within-and between person -estimates. This indicates that, although OC shows no associations on the overall level, some individuals might experience OC-associated mood symptoms. Our findings underscore the importance of accounting for individual differences in experiences during OC use. Furthermore, it raises new questions about mechanisms underlying associations between OC, depression and insomnia. Show less
Gast, D.A.A.; Wit, G.L.C. de; Hoof, A. van; Vries, J.H.M. de; Hemert, B. van; Didden, R.; Giltay, E.J. 2021
Background We sought to assess diet quality among people with intellectual disabilities or borderline intellectual functioning, living in residential facilities or receiving day care. Methods We... Show moreBackground We sought to assess diet quality among people with intellectual disabilities or borderline intellectual functioning, living in residential facilities or receiving day care. Methods We measured diet quality using the Dutch Healthy Diet Food Frequency Questionnaire (DHD) and compared this between participants with (n = 151) and controls without intellectual disabilities (n = 169). Potential correlates of diet quality were explored. Results We found lower mean diet quality among people with intellectual disabilities (M = 80.9) compared to controls (M = 111.2; mean adjusted difference -28.4; 95% CI [-32.3, -24.5]; p < .001). Participants with borderline intellectual functioning and mild intellectual disabilities had lower diet quality and higher body mass index than individuals with severe to profound intellectual disabilities. Being female was a predictor of better diet quality. Conclusions Overall, we found that diet quality was low in the sample of people with intellectual disabilities or borderline intellectual functioning. Show less
