The clinical effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: results from a multicenter, pragmatic randomized controlled trial.

BACKGROUND: Persistent depressive disorder (PDD) is prevalent and debilitating. For patients with PDD, psychiatric rehabilitation using self-management interventions is advised as the next therapeutic step after multiple unsuccessful treatment attempts. The "Patient and Partner Education Program for All Chronic Diseases" (PPEP4All) is a brief, structured self-management program that focuses on functional recovery for patients and their partners/caregivers. In chronic somatic disorder populations, PPEP4All has already been shown to be clinically effective. We examined whether PPEP4All adapted for PDD (PPEP4All-PDD, nine weekly group or individual sessions) is also clinically effective for adults/elderly with PDD and their partners/caregivers compared to care-as-usual (CAU) in specialized mental healthcare. METHODS: In this mixed-method multicenter pragmatic randomized controlled trial, 70 patients with PDD and 14 partners/caregivers were allocated to either PPEP4All-PDD (patients, n = 37; partners/caregivers, n = 14) or CAU (patients, n = 33; partners/caregivers, not included) and completed questionnaires at 0, 3, 6, and 12 months regarding depressive symptoms, psychopathology, psychosocial burden, mental resilience, and happiness/well-being. Qualitative data were collected regarding treatment satisfaction. Data were analyzed using mixed model analyses and an intention-to-treat (ITT) approach. RESULTS: There was no statistically significant difference in any outcome regarding clinical effectiveness between PPEP4All-PDD and CAU. Subgroup analysis for depressive symptoms did not show any interaction effect for any subgroup. Although 78% of participants recommended PPEP4All-PDD, there was no difference in treatment satisfaction between PPEP4All-PDD (score = 6.6; SD = 1.7) and CAU (score = 7.6; SD = 1.2), p = 0.06. CONCLUSION: Although depressive symptoms did not improve relative to CAU, this only confirmed that treatment for patients with treatment-resistant PDD should move from symptom reduction to functional recovery. Also, functional recovery may be reflected in other outcomes than psychosocial burden, such as self-empowerment, in patients with treatment-resistant PDD. Future research on PPEP4All-PDD could focus on a longer-term program and/or online program that may also be offered earlier in the treatment process as an empowerment intervention.  TRIAL REGISTRATION: Netherlands Trial Register Identifier NL5818. Registered on 20 July 2016 https://clinicaltrialregister.nl/nl/trial/20302.

Breaking the cycle: Identifying key symptom pathways of eating disorders and the influence of childhood maltreatment.

BACKGROUND: Most network analyses on central symptoms in eating disorders (EDs) have been cross-sectional. Longitudinal within-person analyses of therapy processes are scarce. Our aim was to investigate central change processes in therapy in a transdiagnostic sample, considering the influence of childhood maltreatment. METHOD: We employed dynamic time warping analyses to identify clusters of symptoms that tended to change similarly across therapy on a within-person level. Symptoms were measured by a 28-item Eating Disorder Examination Questionnaire (EDE-Q). Furthermore, we examined the temporal direction of symptom change to identify symptoms that tended to precede and predict other symptoms. Finally, we estimated two directed, temporal networks in patients with and without a history of childhood maltreatment. RESULTS: Our analysis included 122 ED patients (mean age = 30.9, SD = 9.7; illness duration = 14.2 years, SD = 8.9; prior treatment = 5.6 years, SD = 5.1). The initial network revealed three robust clusters of symptoms over time: (1) ED behavior, (2) inhibition, and (3) cognitions and feelings about body and weight. Overvaluation of shape had the highest out-strength preceding and predicting other symptoms. Dissatisfaction with weight preceded and predicted other symptoms in the maltreatment network. The non-maltreatment network showed a similar structure to the transdiagnostic network. CONCLUSION: Targeting and monitoring feelings and cognitions related to shape may be crucial for achieving lasting symptom improvement in a transdiagnostic sample. Furthermore, our findings highlight the need for further investigation into the different processes driving EDs based on maltreatment status. PUBLIC SIGNIFICANCE: There is limited understanding of the processes that occur for patients with eating disorders between admission and discharge in therapy, especially for patients with a history of childhood maltreatment. Our analyses suggest that changes in cognitions regarding shape precede and predict changes in cognitions about weight. Different processes may be driving the eating disorder according to maltreatment status, which might further illuminate the riddle of dropout and relapse in therapy for patients with a history of childhood maltreatment. These findings suggest the need for further investigation into the specific dynamics occurring during therapy for individuals with a history of childhood maltreatment.

Metabolic syndrome after childhood trauma: a 9-year longitudinal analysis.

BACKGROUND: Childhood trauma (CT) has been cross-sectionally associated with metabolic syndrome (MetS), a group of biological risk factors for cardiometabolic disease. Longitudinal studies, while rare, would clarify the development of cardiometabolic dysregulations over time. Therefore, we longitudinally investigated the association of CT with the 9-year course of MetS components. METHODS: Participants (N = 2958) from the Netherlands Study of Depression and Anxiety were assessed four times across 9 years. The CT interview retrospectively assessed childhood emotional neglect and physical, emotional, and sexual abuse. Metabolic outcomes encompassed continuous MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, blood pressure [BP], and glucose) and count of clinically elevated MetS components. Mixed-effects models estimated sociodemographic- and lifestyle-adjusted longitudinal associations of CT with metabolic outcomes over time. Time interactions evaluated change in these associations. RESULTS: CT was reported by 49% of participants. CT was consistently associated with increased waist (b = 0.32, s.e. = 0.10, p = 0.001), glucose (b = 0.02, s.e. = 0.01, p < 0.001), and count of MetS components (b = 0.04, s.e. = 0.01, p < 0.001); and decreased HDL cholesterol (b = -0.01, s.e.<0.01, p = .020) and systolic BP (b = -0.33, s.e. = 0.13, p = 0.010). These associations were mainly driven by severe CT and unaffected by lifestyle. Only systolic BP showed a CT-by-time interaction, where CT was associated with lower systolic BP initially and with higher systolic BP at the last follow-up. CONCLUSIONS: Over time, adults with CT have overall persistent poorer metabolic outcomes than their non-maltreated peers. Individuals with CT have an increased risk for cardiometabolic disease and may benefit from monitoring and early interventions targeting metabolism.

Lithium in bipolar depression: A review of the evidence.

BACKGROUND: Lithium is widely used as treatment of acute mania and as prophylactic therapy for bipolar disorder. International and national guidelines also consider lithium as a possible treatment of acute bipolar depression. Research on the use of lithium in bipolar depression, however, seems to be limited compared to the data available for its efficacy in the other phases of bipolar disorder. OBJECTIVE: To provide a systematic review of the evidence for lithium in the treatment of acute bipolar depression and provide directions for further research. METHOD: A systematic review of clinical studies investigating the use of lithium in bipolar depression was performed using preferred reporting items for systematic reviews and meta-analyses guidelines in Pubmed, Embase and Psychinfo using the medical subjects headings and free text terms "lithium," "bipolar depression," "dosage," "serum concentration" and "bipolar disorders." RESULTS: This review included 15 studies with a total of 1222 patients, between the age of 18 and 65, suffering from bipolar depression of which 464 were treated with lithium. There are currently only limited and low-quality data on the efficacy of lithium as a treatment of bipolar depression. It appears that there have been no placebo controlled randomized controlled trials with lithium concentrations that are considered to be therapeutic. The older studies suffered from limitations such as small sample sizes, insufficient treatment lengths, and insufficient monitoring of serum concentrations. CONCLUSION: In contrast to data for the treatment of mania and prophylaxis, robust data on the efficacy of lithium in bipolar depression is currently lacking, making it impossible to make conclusions regarding efficacy or inefficacy, for which further research is needed.

The impact of COVID-19-pandemic-related adversity on mental health: longitudinal study in Dutch populations with and without mental health disorders.

BACKGROUND: Despite growing concerns about mental health during the COVID-19 pandemic, particularly in people with pre-existing mental health disorders, research has shown that symptoms of depression and anxiety were generally quite stable, with modest changes in certain subgroups. However, individual differences in cumulative exposure to COVID-19 stressors have not been yet considered. AIMS: We aimed to quantify and investigate the impact of individual-level cumulative exposure to COVID-19-pandemic-related adversity on changes in depressive and anxiety symptoms and loneliness. In addition, we examined whether the impact differed among individuals with various levels of pre-pandemic chronicity of mental health disorders. METHOD: Between April 2020 and July 2021, 15 successive online questionnaires were distributed among three psychiatric case-control cohorts that started in the 2000s (N = 1377). Outcomes included depressive and anxiety symptoms and loneliness. We developed a COVID-19 Adversity Index (CAI) summarising up to 15 repeated measures of COVID-19-pandemic-related exposures (e.g. exposure to COVID-19 infection, negative economic impact and quarantine). We used linear mixed linear models to estimate the effects of COVID-19-related adversity on mental health and its interaction with pre-pandemic chronicity of mental health disorders and CAI. RESULTS: Higher CAI scores were positively associated with higher increases in depressive symptoms, anxiety symptoms and loneliness. Associations were not statistically significantly different between groups with and without (chronic) pre-pandemic mental health disorders. CONCLUSIONS: Individual differences in cumulative exposure to COVID-19-pandemic-related adversity are important predictors of mental health, but we found no evidence for higher vulnerability among people with (chronic) pre-pandemic mental health disorders.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

Temporal associations between salivary cortisol and emotions in clinically depressed individuals and matched controls: A dynamic time warp analysis.

Depression can be understood as a complex dynamic system where depressive symptoms interact with one another. Cortisol is suggested to play a major role in the pathophysiology of depression, but knowledge on the temporal interplay between cortisol and depressive symptoms is scarce. We aimed to analyze the temporal connectivity between salivary cortisol and momentary affective states in depressed individuals and controls. Thirty pair-matched depressed and non-depressed participants completed questionnaires on momentary positive (PA) and negative (NA) affect and collected saliva three times a day for 30 days. The association between cortisol and affect was analyzed by dynamic time warp (DTW) analyses. These analyses involved lag-1 backward to lag-1 forward undirected analyses and lag-0 and lag-1 forward directed analyses. Large inter- and intra-individual variability in the networks were found. At the group level, with undirected analysis PA and NA were connected in the networks in depressed individuals and in controls. Directed analyses indicated that increases in cortisol preceded specific NA items in controls, but tended to follow upon specific affect items increase in depressed individuals. To conclude, at group level, changes in cortisol levels in individuals diagnosed with a depression may be a result of changes in affect, rather than a cause.

PTSD Symptom dynamics after the great east japan earthquake: mapping the temporal structure using Dynamic Time Warping.

Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system.

Personnel from the Japan Ground Self-Defense Force responded to the aftermath of the 2011 Great East Japan Earthquake, putting them at increased risk of developing symptoms of Post-Traumatic Stress Disorder.In recent years, psychological research has focused increasingly on methods to map the ways in which symptoms of psychopathology cause and exacerbate each other.The Dynamic Time Warping algorithm seems to be an appropriate and useful tool to analyse the interaction between post-traumatic stress symptoms over time, especially if these are not instantaneous or linear. This can improve our understanding of psychopathology and help move towards personalized medicine.

Weighing poor immunometabolic health in relatives for severity of affective symptoms: A study of patients with depressive and anxiety disorders and their siblings.

BACKGROUND: Affective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands' immunometabolic health on siblings' psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. METHODS: The sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. RESULTS: In siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. CONCLUSIONS: Our findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.

Metabolomics signatures of depression: the role of symptom profiles.

Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an "atypical/energy-related" symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An 'AES profile' score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (ß = 0.13, p = 1.35*10-12), isoleucine (ß = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (ß = 0.11, p = 6.19*10-9) and saturated fatty acid levels (ß = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (ß = -0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature-commonly linked to cardiometabolic disorders-associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression's detrimental impact on health.

A network analysis of depressive symptoms and metabolomics.

BACKGROUND: Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models. METHODS: We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later. RESULTS: The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave. CONCLUSIONS: The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.

Association Between the Fronto-Limbic Network and Cognitive and Emotional Functioning in Individuals With Bipolar Disorder: A Systematic Review and Meta-analysis.

Importance: Individuals with bipolar disorder (BD) experience cognitive and emotional dysfunctions. Various brain circuits are implicated in BD but have not been investigated in a meta-analysis of functional magnetic resonance imaging (fMRI) studies. Objective: To investigate the brain functioning of individuals with BD compared with healthy control individuals in the domains of emotion processing, reward processing, and working memory. Data Sources: All fMRI experiments on BD published before March 2020, as identified in a literature search of PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Emcare, Academic Search Premier, and ScienceDirect. The literature search was conducted on February 21, 2017, and March 2, 2020, and data were analyzed from January 2021 to January 2022. Study Selection: fMRI experiments comparing adult individuals with BD and healthy control individuals were selected if they reported whole-brain results, including a task assessing at least 1 of the domains. In total, 2320 studies were screened, and 253 full-text articles were evaluated. Data Extraction and Synthesis: A total of 49 studies were included after selection procedure. Coordinates reporting significant activation differences between individuals with BD and healthy control individuals were extracted. Differences in brain region activity were tested using the activation likelihood estimation method. Main Outcomes and Measures: A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to stimuli in 3 cognitive domains between individuals with BD and healthy control individuals were different. Results: The study population included 999 individuals with BD (551 [55.2%] female) and 1027 healthy control individuals (532 [51.8%] female). Compared with healthy control individuals, individuals with BD showed amygdala and hippocampal hyperactivity and hypoactivation in the inferior frontal gyrus during emotion processing (20 studies; 324 individuals with BD and 369 healthy control individuals), hyperactivation in the orbitofrontal cortex during reward processing (9 studies; 195 individuals with BD and 213 healthy control individuals), and hyperactivation in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex during working memory (20 studies; 530 individuals with BD and 417 healthy control individuals). Limbic hyperactivation was only found during euthymia in the emotion and reward processing domains; abnormalities in frontal cortex activity were also found in individuals with BD with mania and depression. Conclusions and Relevance: This systematic review and meta-analysis revealed evidence for activity disturbances in key brain areas involved in cognitive and emotion processing in individuals with BD. Most of the regions are part of the fronto-limbic network. The results suggest that aberrations in the fronto-limbic network, present in both euthymic and symptomatic individuals, may be underlying cognitive and emotional dysfunctions in BD.

Heterogeneity in depressive and anxiety symptoms and loneliness during the COVID-19 pandemic: Results from three Dutch psychiatric case-control cohorts from April 2020 to February 2022.

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 differences in socio-demographic and clinical characteristics. METHOD: We conducted sixteen rounds of questionnaires between April 2020 and February 2022 among participants (n = 1722) of three psychiatric case-control cohorts that started in the 2000's. We used Growth Mixture Modelling and (multinomial) logistic regression to identify characteristics associated with trajectory membership. RESULTS: We found low decreasing (1228 [72%] participants), intermediate (n = 348 [22%] participants) and high stable (106 [6%] participants) trajectories of depressive symptoms; decreasing low/intermediate (1507 [90%] participants) and high stable (161 [10%] participants) trajectories of anxiety symptoms; and stable low (1109 [61%] participants), stable high (315 [17%] participants), temporary lowered (123 [9%]) and temporary heightened (175 [13%] participants) trajectories of loneliness. Chronicity and severity of pre-pandemic mental disorders predicted unfavourable sub-group membership for all outcomes. Being female, having a low education and income level were associated with unfavourable trajectories of depression, being younger with unfavourable trajectories of anxiety and being female and living alone with unfavourable trajectories of loneliness. CONCLUSION: We found relatively stable trajectories of depression and anxiety symptoms over two years, suggesting low heterogeneity in outcomes during the pandemic. For loneliness, we found two specific sub-groups with temporary increase and decrease in loneliness during the pandemic.

Translation and cross-cultural validation of the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48).

We aimed to validate cross-culturally the Turkish, Moroccan Arabic and Moroccan Berber versions of the 48-item Symptom Questionnaire (SQ-48). Its psychometric properties were assessed in four samples: patients (n = 150) and controls (n = 103) with Turkish or Moroccan origins (n = 103) and patients (n = 189) and controls (n = 463) with native Dutch origins. Internal consistency and discriminatory power of SQ-48 subscales across groups were adequate to high. However, immigrant groups scored on average higher than Dutch native groups, but there was full configural, metric and partial scalar invariance in the immigrant groups. Although the SQ-48 is a valid measure of psychopathology in immigrant groups of Turkish and Moroccan origins, their cut-off values should likely be higher compared to natives.

Use of benzodiazepine and Z-drugs and mortality in older adults after myocardial infarction.

BACKGROUND: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI). METHODS: This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors. RESULTS: A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent-patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: <0.001). CONCLUSION: BZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship. CLINICAL TRIAL REGISTRATION: NCT00127452 (www. CLINICALTRIALS: gov).

Dietary supplements for aggressive behaviour in people with intellectual disabilities: A randomised controlled crossover trial.

BACKGROUND: Aggressive 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. METHODS: We 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). RESULTS: there 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). CONCLUSION: In 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.

Cognitive performance among older adults with psychotic depression compared to non-psychotic depression.

It remains unclear whether psychotic depression (PD) compared to non-psychotic depression (non-PD) among older adults is associated with poorer cognitive performance. For inpatients (60+) with a major depressive episode, cognitive performance in PD and non-PD (categorical) were compared as well as the relationship between symptom severity for depression and psychosis (dimensional) and cognition. Of 90 participants (on average 72.7 years old; range 60-92), 64% were female. The severity of depressive- and psychotic symptoms are both negatively associated with cognitive functioning among older adults with depression. This is of relevance for the treatment of this vulnerable group of patients.

Eating disorder psychopathology dimensions based on individual co-occurrence patterns of symptoms over time: a dynamic time warp analysis in a large naturalistic patient cohort.

PURPOSE: Most of the network approaches in eating disorders found the highest degree of centrality for symptoms related to weight and shape concerns. However, longitudinal analyses are scarce and may increase our insight of the complex characteristics and dynamics over time. In the current study, an alternative non-linear method to perform longitudinal network analyses, the dynamic time warp approach, was used to examine whether robust dimensions of eating disorder psychopathology symptoms could be found based on the individual dynamic interplay of eating disorder symptoms co-occurrence patterns in time. METHODS: The study sample included a naturalistic cohort of patients (N = 255) with all eating disorder subtypes who were assessed with the eating disorder examination questionnaire (EDE-Q) at a minimum of four times during treatment. Dynamic time warp analyses yielded distance matrices within each individual patient, which were subsequently aggregated into symptom networks and dimensions at the group level. RESULTS: Aggregation of the individual distance matrices at the group level yielded four robust symptom dimensions: 1. restraint/rules, 2. secret eating/fasting, 3. worries/preoccupation, and 4. weight and shape concern. The items 'fear of weight gain' and 'guilt' were bridge symptoms between the dimensions 1, 3 and 4. CONCLUSION: Dynamic time warp could capture the within-person dynamics of eating disorder symptoms. Sumscores of the four dimensions could be used to follow patients over time. This approach could be applied in the future to visualize eating disorder symptom dynamics and signal the central symptoms within an individual and groups of patients. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies. .

A randomized pharmacological fMRI trial investigating D-cycloserine and brain plasticity mechanisms in learned pain responses.

Learning and negative outcome expectations can increase pain sensitivity, a phenomenon known as nocebo hyperalgesia. Here, we examined how a targeted pharmacological manipulation of learning would impact nocebo responses and their brain correlates. Participants received either a placebo (n = 27) or a single 80 mg dose of D-cycloserine (a partial NMDA receptor agonist; n = 23) and underwent fMRI. Behavioral conditioning and negative suggestions were used to induce nocebo responses. Participants underwent pre-conditioning outside the scanner. During scanning, we first delivered baseline pain stimulations, followed by nocebo acquisition and extinction phases. During acquisition, high intensity thermal pain was paired with supposed activation of sham electrical stimuli (nocebo trials), whereas moderate pain was administered with inactive electrical stimulation (control trials). Nocebo hyperalgesia was induced in both groups (p < 0.001). Nocebo magnitudes and brain activations did not show significant differences between D-cycloserine and placebo. In acquisition and extinction, there were significantly increased activations bilaterally in the amygdala, ACC, and insula, during nocebo compared to control trials. Nocebo acquisition trials also showed increased vlPFC activation. Increased opercular activation differentiated nocebo-augmented pain aggravation from baseline pain. These results support the involvement of integrative cognitive-emotional processes in nocebo hyperalgesia.