Treatment patterns and clinical outcomes

BACKGROUND: Treatment resistant depression (TRD) characterizes a subgroup of 10-30% of patients with major depressive disorder, and is associated with considerable morbidity and mortality. A consensus treatment for TRD does not exist, which often leads to wide variations in treatment strategies. Real-world studies on treatment patterns and outcomes in TRD patients in Europe are lacking and could help elucidate current treatment strategies and their efficacy. METHODS: This non-interventional cohort study of patients with TRD (defined as treatment failure on ≥2 oral antidepressants given at adequate dose and duration) with moderate to severe depression collected real-world data on treatment patterns and outcomes in several European countries. Patients were started on a new treatment for depression according to routine clinical practice. RESULTS: Among 411 patients enrolled, after 6 months, only 16.7% achieved remission and 73.5% showed no response. At Month 12, while 19.2% achieved remission and 69.2% showed no response, 33.3% of those in remission at Month 6 were no longer in remission. Pharmacological treatments employed were heterogenous; 54 different drugs were recorded at baseline, and the top 5 treatment types according to drug classes accounted for 40.0% of patients. Even though remission rates were very low, at Month 12, 60.0% of patients had not changed treatment since enrolment. CONCLUSIONS: The heterogeneity of treatments highlights a lack of consensus. Moreover, despite low response rates, patients often remained on treatments for substantial periods of time. These data further support existence of an unmet treatment need for TRD patients in Europe.publishersversionpublishe

Understanding personalized dynamics to inform precision medicine: a dynamic time warp analysis of 255 depressed inpatients

Background: Major depressive disorder (MDD) shows large heterogeneity of symptoms between patients, but within patients, particular symptom clusters may show similar trajectories. While symptom clusters and networks have mostly been studied using cross-sectional designs, temporal dynamics of symptoms within patients may yield information that facilitates personalized medicine. Here, we aim to cluster depressive symptom dynamics through dynamic time warping (DTW) analysis. Methods: The 17-item Hamilton Rating Scale for Depression (HRSD-17) was administered every 2 weeks for a median of 11 weeks in 255 depressed inpatients. The DTW analysis modeled the temporal dynamics of each pair of individual HRSD-17 items within each patient (i.e., 69,360 calculated “DTW distances”). Subsequently, hierarchical clustering and network models were estimated based on similarities in symptom dynamics both within each patient and at the group level. Results: The sample had a mean age of 51 (SD 15.4), and 64.7% were female. Clusters and networks based on symptom dynamics markedly differed across patients. At the group level, five dynamic symptom clusters emerged, which differed from a previously published cross-sectional network. Patients who showed treatment response or remission had the shortest average DTW distance, indicating denser networks with more synchronous symptom trajectories. Conclusions: Symptom dynamics over time can be clustered and visualized using DTW. DTW represents a promising new approach for studying symptom dynamics with the potential to facilitate personalized psychiatric care

Healthcare resource utilization

Background: Treatment resistant depression (TRD) is diagnosed when patients experiencing a major depressive episode fail to respond to ≥2 treatments. Along with substantial indirect costs, patients with TRD have higher healthcare resource utilization (HCRU) than other patients with depression. However, research on the economic impact of this HCRU, and differences according to response to treatment, is lacking. Methods: This multicenter, observational study documented HCRU among patients with TRD in European clinical practice initiating new antidepressant treatments. Data regarding access to outpatient consultations and other healthcare resources for the first 6 months, collected using a questionnaire, were analyzed qualitatively according to response and remission status. The economic impact of HCRU, estimated using European costing data, was analyzed quantitatively. Results: Among 411 patients, average HCRU was higher in non-responders, attending five times more general practitioner (GP) consultations and spending longer in hospital (1.7 versus 1.1 days) than responders. Greater differences were observed according to remission status, with non-remitters attending seven times more GP consultations and spending approximately three times longer in hospital (1.7 versus 0.6 days) than remitters. Consequently, the estimated economic impacts of non-responders and non-remitters were significantly greater than those of responders and remitters, respectively. Limitations: Key limitations are small cohort size, absence of control groups and generalizability to different healthcare systems. Conclusion: Patients with TRD, particularly those not achieving remission, have considerable HCRU, with associated economic impact. The costs of unmet TRD treatment needs are thus substantial, and treatment success is fundamental to reduce individual needs and societal costs.publishersversionpublishe

Opening the research agenda for selection of hot spots for human biomonitoring research in Belgium: a participatory research project

<p>Abstract</p> <p>Background</p> <p>In order to select priority hotspots for environment and health research in Flanders (Belgium), an open procedure was organized. Environment and health hotspots are strong polluting point sources with possible health effects for residents living in the vicinity of the hot spot. The selection procedure was part of the work of the Flemish Centre of Expertise for Environment and Health, which investigates the relation between environmental pollution and human health. The project is funded and steered by the Flemish government.</p> <p>Methods</p> <p>The involvement of other actors than merely experts is inspired by the 'analytical-deliberative' approach of the National Research Council in the United States and the extended peer community approach. These approaches stress the importance of involving different expert- and social perspectives in order to increase the knowledge base on complex issues. In the procedure used in the project a combination of expert and stakeholder input was essential. The final decision was supported by a multi-criteria analysis of expert assessment and stakeholder advice.</p> <p>Results</p> <p>The endeavour was challenging from the start because of the complicated ambition of including a diversity of actors, potential hotspots, concerns and assessment criteria, but nevertheless the procedure proved its value in both structuring and informing the decision-making process. Moreover the process gained the support of most actors participating in the process, even though the final selection could not satisfy all preferences.</p> <p>Conclusions</p> <p>Opening the research agenda exemplifies the value of inter- and transdisciplinary cooperation as well as the need for a well-structured and negotiated procedure that combines relevant factors and actors with pragmatism. The value of such a process also needs to prove itself in practice after the procedure has been completed: the tension between an ambition of openness on the one hand and a more closed attitude amongst experts on the other will continue to play a role even after closure.</p

Harmonization of human biomonitoring studies in Europe: characteristics of the HBM4EU-aligned studies participants

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL((R)) DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll((R)) DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed

EEG correlates of impaired self-other integration during joint-task performance in schizophrenia

FSW - Self-regulation models for health behavior and psychopathology - ou

Converging evidence of social avoidant behavior in schizophrenia from two approach-avoidance tasks

FSW - Self-regulation models for health behavior and psychopathology - ou

The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder

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 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.Stress-related psychiatric disorders across the life spa

Supplementary Material for: Unraveling Psychomotor Slowing in Bipolar Disorder

<strong><em>Background/Aims:</em></strong> In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. <b><i>Methods:</i></b> Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. <b><i>Results:</i></b> The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. <b><i>Conclusions:</i></b> The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients