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Highlights
• Suicides which occurred in a biologics trial targeting the IL-17R are revisited.
• High IL-17 levels are found in depression by the majority of reports.
• Results from studies regarding IL-17 and psychosis are mixed.
• Very few psychiatric studies investigated IL-17 signalling in suicidality.
• Potential mechanisms how IL-17 influences neuro-inflammation are described.
Abstract:
Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine which plays a role in autoimmune disorders, such as psoriasis and multiple sclerosis, and is important for the defense against pathogens, particularly in the gut. However, IL-17 has recently also gained attention in association with suicidal behavior. In this review, we review the literature regarding IL-17 in psychiatric disorders and suicidality. We also take a closer look at the suicides which occurred in the clinical trial for psoriasis with brodalumab, a monoclonal antibody targeting the IL-17 receptor. Lastly, we discuss potential working mechanisms relevant to neuroinflammation and the possible involvement of IL-17.
Background: While the antidepressant efficacy of guided digital interventions has been proven in randomized controlled trials, findings from routine care are less clear. Low adherence rates are common and limit the potential effectiveness. Adherence has been linked to sociodemographic variables and the amount of guidance, but the role of the guide's profession and their work setting has not yet been studied for routine care.
Methods: Routinely collected log data from a digital intervention for depressed patients (iFightDepression tool) were analyzed in an exploratory manner. The sample is a convenience sample from routine care, where guidance is provided by general practitioners (GP), certified psychotherapists (PT) or medical doctors specialized in mental health. Log data from 2184 patients were analyzed and five usage parameters were extracted to measure adherence (first-to-last login, time on tool, number of sessions, workshops completed and minimal dose). Multiple logistic regression was used to analyze relations between the guide's profession and clinical context as well as other covariates and adherence and symptom change on a brief depression questionnaire (PHQ-9).
Results: The analyses showed a significant relation of guide profession and adherence. Guidance by PT was associated to the highest adherence scores (reference category). The odds ratios (ORs) of scoring above the median in each usage parameter for patients guided by GPs were 0.50–0.63 (all ps < 0.002) and 0.61–0.80 (p = .002–0.197) for MH. Higher age, initial PHQ-9 score and self-reported diagnosis of depression were also significantly associated with higher adherence scores. In a subsample providing enough data on the PHQ-9 (n = 347), no association of guide profession with symptom reduction was found. Instead, a greater reduction was observed for patients with a higher baseline PHQ-9 (β = −0. 39, t(341.75) = −8.814, p < .001) and for those who had achieved minimal dose (β = −2.42, t(340.34) = −4.174, P < .001) and those who had achieved minimal dose and scored high on time on tool (β = 0.22, t(341.75) = 1.965, P = .050).
Conclusion: Being guided by PT was associated with the highest adherence. The lowest adherence was observed in patients who were guided by GP. While no association of guide profession and symptom reduction was found in a subsample, greater adherence was associated with symptom reduction.
Introduction: The COVID-19 pandemic has necessitated a reduction in face-to-face consultations, resulting in significant limitations in healthcare for individuals with depression. To ensure safe and adequate care, e-health services, such as telemedicine, gained a more prominent role. Governments have eased restrictions on the use of telemedicine, enabling healthcare professionals to increasingly offer video and telephone consultations.
Objective: This study examines, 1) possible changes over the course of the pandemic in reported use of video and telephone consultations and intended future use of video consultations with healthcare professionals among adults with diagnosed depression; 2) their attitudes towards video and telephone consultations and perceived barriers towards using e-health after prolonged time of the pandemic; and 3) differences in results between subgroups based on sociodemographic and clinical characteristics.
Methods: Three population-representative online surveys were conducted in Germany at different timepoints (t) during the COVID-19 pandemic. Respondents aged 18–69 years with a professionally diagnosed depression were included in the present analyses (t1: June/July 2020 with n = 1094; t2: February 2021 with n = 1038; t3: September 2021 with n = 1255).
Results: The overall proportion of adults with depression who used video or telephone consultations did not change significantly in the time surveyed (t1: 16.51 %, n = 179; t2: 20.23 %, n = 210; t3: 18.47 %, n = 230). However, among users, reported use of video consultations with a psychotherapist increased significantly from t1 (34.83 %, n = 62) to t3 (44.98 %, n = 102, p = .023). Intended future use of VC for healthcare varied depending on the purpose of the consultation. Significant differences over time were only found for the purpose of using VC to discuss clinical findings, laboratory results and diagnostic analyses with a doctor, with higher intentions reported at t2 during lockdown in Germany. At t3, the majority of adults with depression felt that video and telephone consultations were too impersonal and considered them more as a helpful support rather than an alternative to face-to-face psychotherapy. Key barriers to using e-health were found within the societal context and the lacking support from significant others for using e-health, while knowledge and skills represented facilitators for using e-health.
Conclusion: Despite ambivalent attitudes towards video and telephone consultations among adults with depression, reported use of video consultations with a psychotherapist increased during the COVID-19 pandemic.
Pattern recognition approaches, such as the Support Vector Machine (SVM), have been successfully used to classify groups of individuals based on their patterns of brain activity or structure. However these approaches focus on finding group differences and are not applicable to situations where one is interested in accessing deviations from a specific class or population. In the present work we propose an application of the one-class SVM (OC-SVM) to investigate if patterns of fMRI response to sad facial expressions in depressed patients would be classified as outliers in relation to patterns of healthy control subjects. We defined features based on whole brain voxels and anatomical regions. In both cases we found a significant correlation between the OC-SVM predictions and the patients' Hamilton Rating Scale for Depression (HRSD), i.e. the more depressed the patients were the more of an outlier they were. In addition the OC-SVM split the patient groups into two subgroups whose membership was associated with future response to treatment. When applied to region-based features the OC-SVM classified 52% of patients as outliers. However among the patients classified as outliers 70% did not respond to treatment and among those classified as non-outliers 89% responded to treatment. In addition 89% of the healthy controls were classified as non-outliers.
Supported by the German Alliance Against Depression, 82 regions in Germany launched their own community-based multi-level intervention programs targeting both depression and suicidal behavior prior to January 2016. Sixteen of these regions have implemented the full 4-level intervention program comprising 1) training of General Practitioners, 2) a public awareness campaign, 3) training of community facilitators and 4) support for depressed patients and their relatives for at least three years. The aim of the study was to examine possible suicide prevention effects in these sixteen 4-level intervention regions (comprising a population of 6,976,309) by 1) comparing the annual suicide rates during the 3-year intervention period to a 10-year baseline and 2) comparing these differences to corresponding trends in Germany after excluding all intervention regions (Germany-IR). Primary outcome was the annual rate of suicides. Analyses included negative binomial regression models. When examining differences between suicide rates during the intervention period compared to the baseline period, only a trend towards a significant reduction was found. This reduction of suicides in the sixteen 4-level intervention regions did not differ from that in Germany-IR as control. The interpretation of these findings has to take into account that the training of General Practitioners, police and other community facilitators might have improved the recognition of suicides, thus increasing detection rates. Furthermore, destigmatizing effects of the public awareness campaigns might have increased the number of suicides by lowering suicide threshold (“normalization”) for those at risk and by decreasing the rate of suicides deliberately hidden by suicide victims or their relatives.
Depressive symptoms in youth with ADHD: the role of impairments in cognitive emotion regulation
(2022)
Youth with attention-deficit/hyperactivity disorder (ADHD) are at increased risk to develop co-morbid depression. Identifying factors that contribute to depression risk may allow early intervention and prevention. Poor emotion regulation, which is common in adolescents, is a candidate risk factor. Impaired cognitive emotion regulation is a fundamental characteristic of depression and depression risk in the general population. However, little is known about cognitive emotion regulation in youth with ADHD and its link to depression and depression risk. Using explicit and implicit measures, this study assessed cognitive emotion regulation in youth with ADHD (N = 40) compared to demographically matched healthy controls (N = 40) and determined the association with depressive symptomatology. As explicit measure, we assessed the use of cognitive emotion regulation strategies via self-report. As implicit measure, performance in an ambiguous cue-conditioning task was assessed as indicator of affective bias in the processing of information. Compared to controls, patients reported more frequent use of maladaptive (i.e., self-blame, catastrophizing, and rumination) and less frequent use of adaptive (i.e., positive reappraisal) emotion regulation strategies. This pattern was associated with the severity of current depressive symptoms in patients. In the implicit measure of cognitive bias, there was no significant difference in response of patients and controls and no association with depression. Our findings point to depression-related alterations in the use of cognitive emotion regulation strategies in youth with ADHD. The study suggests those alterations as a candidate risk factor for ADHD-depression comorbidity that may be used for risk assessment and prevention strategies.
Circulating monocytes contribute to inflammatory processes. We here validate abnormal expression of inflammation-related genes in monocytes of a large and well-characterised group of MDD patients, and relate the outcomes to pertinent clinical characteristics. Thirty-two genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD, and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene- expression data were related to age, sex, BMI, depression severity, childhood adversity (CA) and suicide risk (SR). Three distinct gene profiles were identified within the MDD group (downregulated, mixed upregulated and strongly upregulated genes). Patients in the merged upregulated groups had a significantly higher prevalence of CA and high SR. Using hierarchical clustering of the genes, we found a cluster of mainly cytokine (production)-related genes; patients with SR had a significantly higher expression of this cluster than patients without SR (particularly for IL-6, IL1A and IL1B). Such difference did not emerge for patients with and without CA. A downregulated gene profile was found for patients not exposed to CA and without SR (particularly for glucocorticoid-signalling genes NR3C1a and HSPA1/B). No inflammatory changes were observed for healthy controls exposed to CA. Our data show that inflammatory activation in MDD is not uniform, and that immunologically discernible phenotypes of depression can be linked to CA and high SR. The absence of monocyte inflammatory activation in healthy controls exposed to CA suggests an inflammatory involvement in MDD-prone individuals exposed to early stressors, but not healthy controls.
Background: Depression and anxiety are the most prevalent mental health difficulties in the workplace, costing the global economy $1 trillion each year. Evidence indicates that symptoms may be reduced by interventions in the workplace. This paper is the first to systematically review psychosocial interventions for depression, anxiety, and suicidal ideation and behaviours in small-to medium-size enterprises (SMEs).
Methods: A systematic search following PRISMA guidelines, registered in PROSPERO (CRD42020156275), was conducted for psychosocial interventions targeting depression, anxiety, and suicidal ideation/behaviour in SMEs. The PubMed, PsycINFO, Scopus, and two specific occupational health databases were searched, as well as four databases for grey literature, without time limit until 2nd December 2019.
Results: In total, 1283 records were identified, 70 were retained for full-text screening, and seven met the inclusion criteria: three randomised controlled trials (RCTs), three before and after designs and one non-randomised trial, comprising 5111 participants. Study quality was low to moderate according to the Quality Assessment Tool for Quantitative Studies. Five studies showed a reduction in depression and anxiety symptoms using techniques based on cognitive behavioural therapy (CBT), two reported no significant change.
Limitations: Low number and high heterogeneity of interventions and outcomes, high attrition and lack of rigorous RCTs.
Conclusions: Preliminary evidence indicates CBT-based interventions can be effective in targeting symptoms of depression and anxiety in SME employees. There may be unique challenges to implementing programmes in SMEs. Further research is needed in this important area.
The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ = − 3.46, t(165) = − 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ = − 1.00, t(165) = − 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results.
Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)‐guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.
Methods and results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP‐guided HF management. One‐year rates of freedom from device‐ or system‐related complications and from sensor failure (co‐primary outcomes) were 98.3% [95% confidence interval (CI) 95.8–100.0] and 99.6% (95% CI 97.6–100.0), respectively. Survival rate was 86.2%. For the 12 months post‐ vs. pre‐implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient‐year; hazard ratio 0.38, 95% CI 0.31–0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9‐item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).
Conclusion: Haemodynamic‐guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician‐directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.