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... Show moreDepression 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. Show less
BackgroundMost 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... Show moreBackgroundMost 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.MethodWe 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.ResultsOur 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.ConclusionTargeting 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. Show less
Does, F.H.S. van der; Nagamine, M.; Wee, N.J.A. van der; Chiba, T.; Edo, N.; Kitano, M.; ... ; Giltay, E.J. 2023
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... Show moreBackground: 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. Show less
BackgroundChildhood trauma (CT) has been cross-sectionally associated with metabolic syndrome (MetS), a group of biological risk factors for cardiometabolic disease. Longitudinal studies, while... Show moreBackgroundChildhood 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.MethodsParticipants (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.ResultsCT 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.ConclusionsOver 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. Show less
Maran, P.L.; Klokgieters, S.S.; Giltay, E.J.; Oppen, P. van; Jörg, F.; Eikelenboom, M.; ... ; Kok, A.A.L. 2023
BackgroundDespite 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... Show moreBackgroundDespite 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.AimsWe 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.MethodBetween 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.ResultsHigher 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.ConclusionsIndividual 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. Show less
BackgroundChildhood trauma (CT) is associated with severe sequelae, including stress-related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship... Show moreBackgroundChildhood trauma (CT) is associated with severe sequelae, including stress-related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship seems to be emotion regulation. We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger in a cohort that included participants with and without current affective disorders.MethodsIn the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi-structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at a 4-year follow-up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ-4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post hoc analyses comprised cross-sectional regression analyses, using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) also obtained at a 4-year follow-up.ResultsParticipants (n = 2271) were on average 42.1 years (SD = 13.1), and 66.2% were female. Childhood trauma showed a dose–response association with all anger constructs. All types of childhood trauma were significantly associated with borderline personality traits, independently of depression and anxiety. Additionally, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood. Cross-sectionally, the effect sizes were larger compared with the analyses with the childhood trauma measured 4 years prior to the anger measures.ConclusionsChildhood trauma is linked with anger in adulthood, which could be of particular interest in the context of psychopathology. Focus on childhood traumatic experiences and adulthood anger may help to enhance the effectiveness of treatment for patients with depressive and anxiety disorders. Trauma-focused interventions should be implemented when appropriate. Show less
BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic... Show moreBackgroundAffective (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.MethodsThe 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.ResultsIn 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.ConclusionsOur 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. Show less
Kluiver, H. de; Jansen, R.; Penninx, B.W.J.H.; Giltay, E.J.; Schoevers, R.A.; Milaneschi, Y. 2023
Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous... Show moreDepression 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 (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = −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. Show less
BackgroundManic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic... Show moreBackgroundManic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time.MethodsThe Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3–6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network.ResultsThe mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the “Lethargy” dimension showed the highest out-strength, and its changes preceded those of “somatic/suicidality,” while changes in “core (hypo)mania” preceded those of “dysphoric mania.”ConclusionDynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention. Show less
BackgroundDepression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network... Show moreBackgroundDepression 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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. Show less
Mesbah, R.; Koenders, M.A.; van der Wee, N.J.A.; Giltay, E.J.; van Hemert, A.M.; de Leeuw, M. 2023
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... Show moreWe 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. Show less
Hebbrecht, K.; Dejaeger, M.; Giltay, E.J.; Birkenhager, T.; Sabbe, B.; Verwijk, E.; ... ; Diermen, L. van 2023
ObjectiveWhile 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... Show moreObjectiveWhile 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.MethodWe 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.ResultsWe 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.ConclusionWe 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. Show less
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... Show moreBackground: 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. Show less
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... Show morePurpose: 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. Show less
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... Show moreLearning 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. Show less
Gast, D.A.A.; Didden, R.; Westera, J.J.; Rest, O. van de; Hemert, A.M. van; Giltay, E.J. 2022
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
