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BACKGROUND: Suicide is a global health concern whose rates are soaring in many low-and-middle-income countries. Public awareness campaigns have been implemented in Brazil; however, their impact is uncertain. METHODS: This was an ecological study using population data from DATA-SUS, a Brazilian official notification system, selecting only deaths that were voluntarily self-inflicted (CID-10 × 60-X84). We analyzed all available data from 2000 to 2019 to assess trends before and after the national Yellow September (YS) campaign started in 2015. Differences in trends were assessed by Joinpoint Analysis (JA) and Regression Discontinuity Analysis (RDD), unadjusted and adjusted for economic factors. RESULTS: Overall, there was a progressive increase in the rate of relative (per 100,000 inhabitants) number of suicides over time between 2000 and 2019 (57 % increase). The JA detected a change in the slope of the curve representing an acceleration in suicides starting in the year 2015. Adjusted RDD revealed the year that Yellow September started significantly change the slope of the association between time and rates of suicide (pinteraction < 0.01), and marginal analysis detected the coefficient increased from 0.07 (95%CI 0.04-0.10) to 0.27 (95%CI -0.07-0.60) suicides/year per 100,000 inhabitants. LIMITATIONS: The ecological nature of the manuscript compromises causational implications. CONCLUSIONS: We found an increase in suicidal trends in Brazil, against the global trend that coincides with the beginning of a large national awareness campaign. Although we cannot attribute causality, our results reinforce the need of further studies to better understand the role of awareness campaigns in suicide reduction interventions, including potential unintended effects.
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Internet-based cognitive behavioral therapy (iCBT) offers a scalable, cost-effective, accessible, and low-threshold form of psychotherapy. Recent advancements explored the use of conversational agents such as chatbots and voice assistants to enhance the delivery of iCBT. These agents can deliver iCBT-based exercises, recognize and track emotional states, assess therapy progress, convey empathy, and potentially predict long-term therapy outcome. However, existing systems predominantly utilize categorical approaches for emotional modeling, which can oversimplify the complexity of human emotional states. To address this, we developed a transformer-based model for dimensional text-based emotion recognition, fine-tuned with a novel, comprehensive dimensional emotion dataset comprising 75,503 samples. This model significantly outperforms existing state-of-the-art models in detecting the dimensions of valence, arousal, and dominance, achieving a Pearson correlation coefficient of r = 0.90, r = 0.77, and r = 0.64, respectively. Furthermore, a feasibility study involving 20 participants confirmed the model's technical effectiveness and its usability, acceptance, and empathic understanding in a conversational agent-based iCBT setting, marking a substantial improvement in personalized and effective therapy experiences.
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BACKGROUND: Prolonged exposure (PE) therapy is widely recognized as an effective treatment for post-traumatic stress disorder (PTSD) and is often considered one of the primary options for addressing this condition. Nevertheless, a significant proportion of patients (30-51%) fail to demonstrate clinically significant symptom changes. One of the reasons is that a high proportion of patients drop out from treatment, which often lasts for a minimum of 3-4 months. Hence, there is an urgent need for PTSD treatments that can be delivered to decrease dropout rates. A more intensive PE treatment approach has been suggested to decrease dropout rates and in addition achieve faster recovery rates and has shown promising effects on reducing PTSD symptoms but needs to be tested against firsthand treatment. METHODS: This single-blind, randomized controlled trial (N = 140) will compare an intensive delivery format of prolonged exposure (iPE) against standard weekly delivered sessions of PE. The primary outcome is change on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes include self-rated measures of symptoms of PTSD and complex PTSD, depression and quality of life, speed of recovery, cost effectiveness, dropout rates, and adverse events. DISCUSSION: This study will be the first to compare iPE with first-line treatment in a psychiatric outpatient setting. One of the key strengths of this study lies in its implementation within a clinical setting and the broad eligibility criteria. Additionally, the utilization of gold-standard assessment measures ensures the accuracy and reliability of the outcomes. However, several potential challenges may arise during the study's execution. These challenges may include difficulties in participant recruitment, ensuring adequate participant retention, adherence to the treatment protocol, and maintaining therapist retention mostly due to recruitment taking place at one single clinic. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05934175. Registered on June 6, 2023. Open Science Framework (OSF) https://osf.io/7qsb3 . Registered on September 2, 2023.
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Estudos de Equivalência como Asunto , Terapia Implosiva , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Método Simples-Cego , Terapia Implosiva/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto , Pacientes Desistentes do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Qualidade de Vida , Masculino , FemininoRESUMO
BACKGROUND: Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm-including nonsuicidal self-injuries and suicide attempts-and death by suicide in BDD. METHODS: Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997, and December 31, 2020, were matched with 10 unexposed individuals (i.e., without BDD) from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios and 95% CIs for intentional self-harm. Stratified Cox proportional hazards models estimated hazard ratios and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities. RESULTS: Among 2833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1071 (3.78%), respectively, had at least 1 record of intentional self-harm during the study period (incidence rate ratio = 3.37; 95% CI, 3.02-3.76). In the BDD group, about two-thirds (n = 314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (hazard ratio = 3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least 1 previous record of intentional self-harm compared with unexposed individuals (52.94% vs. 22.22%; p = .036). CONCLUSIONS: BDD was associated with a 3-fold increased risk of intentional self-harm and death by suicide.
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INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.
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Transtorno Obsessivo-Compulsivo , Avaliação de Resultados em Cuidados de Saúde , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico , Adulto , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de RemissãoRESUMO
Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G>A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD.
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While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.
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Background: Trauma-focused cognitive behavioural therapy such as prolonged exposure is considered firsthand choice for treatment of posttraumatic stress disorder (PTSD) but is seldom available in regular care. Digital therapy is proposed to bridge this gap, but its effectiveness for severe and complex PTSD is uncertain. The primary objective of the current study was to examine the feasibility, acceptability, and preliminary effects of digital therapist-guided prolonged exposure (Huddinge Online Prolonged Exposure; HOPE).Method: Thirty participants with moderate to severe PTSD, with the majority self-reporting complex PTSD symptoms, received HOPE over a ten-week period. Eighty percent of participants had been diagnosed with other psychiatric comorbidity by a mental health professional. Primary outcome was the feasibility and acceptability of treatment. Participants were repeatedly assessed using clinician- and self-rated outcome measures at baseline, during the treatment period, post-treatment, and at 1-month and 6-month follow-ups to estimate preliminary treatment effects. The Clinician Administered PTSD Scale version 5 (CAPS-5), administered by independent assessors, evaluated PTSD symptom severity.Results: HOPE proved feasible and effective, delivering evidence-based treatment content in a psychiatric outpatient setting with reduced therapist time. The treatment was well-tolerated, with no severe adverse events and a 17% dropout rate. Sixty-four percent completed the exposure-based portion of the treatment, and overall satisfaction measured by the Client Satisfaction Questionnaire was moderate. Furthermore, significant reductions in PTSD symptoms as assessed with the CAPS-5 (Cohen's d = 1.30 [95% CI -1.79 to -0.82]) at the primary endpoint 1 month which were sustained at the 6-month follow up.Conclusion: Altogether, this study indicate feasibility of treating severe and complex PTSD through a digital PE intervention, thereby building upon and extending previous research findings. Large-scale controlled trials are needed to further validate the specific effect and long-term benefits of HOPE.Trial registration: ClinicalTrials.gov identifier: NCT05560854.
HOPE, a digital therapist-guided prolonged exposure programme, demonstrated feasibility and preliminary effects for severe and complex PTSD in a psychiatric outpatient setting, while requiring less therapist time.HOPE was well-tolerated by participants, with a relatively low dropout rate and average overall satisfaction.Significant reductions in PTSD symptoms were observed, and these benefits were sustained at the 6-month follow-up.
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Terapia Cognitivo-Comportamental , Terapia Implosiva , Transtornos de Estresse Pós-Traumáticos , Humanos , Estudos de Viabilidade , Transtornos de Estresse Pós-Traumáticos/terapia , Pessoal de SaúdeRESUMO
To date, four genome-wide association studies (GWAS) of obsessive-compulsive disorder (OCD) have been published, reporting a high single-nucleotide polymorphism (SNP)-heritability of 28% but finding only one significant SNP. A substantial increase in sample size will likely lead to further identification of SNPs, genes, and biological pathways mediating the susceptibility to OCD. We conducted a GWAS meta-analysis with a 2-3-fold increase in case sample size (OCD cases: N = 37,015, controls: N = 948,616) compared to the last OCD GWAS, including six previously published cohorts (OCGAS, IOCDF-GC, IOCDF-GC-trio, NORDiC-nor, NORDiC-swe, and iPSYCH) and unpublished self-report data from 23andMe Inc. We explored the genetic architecture of OCD by conducting gene-based tests, tissue and celltype enrichment analyses, and estimating heritability and genetic correlations with 74 phenotypes. To examine a potential heterogeneity in our data, we conducted multivariable GWASs with MTAG. We found support for 15 independent genome-wide significant loci (14 new) and 79 protein-coding genes. Tissue enrichment analyses implicate multiple cortical regions, the amygdala, and hypothalamus, while cell type analyses yielded 12 cell types linked to OCD (all neurons). The SNP-based heritability of OCD was estimated to be 0.08. Using MTAG we found evidence for specific genetic underpinnings characteristic of different cohort-ascertainment and identified additional significant SNPs. OCD was genetically correlated with 40 disorders or traits-positively with all psychiatric disorders and negatively with BMI, age at first birth and multiple autoimmune diseases. The GWAS meta-analysis identified several biologically informative genes as important contributors to the aetiology of OCD. Overall, we have begun laying the groundwork through which the biology of OCD will be understood and described.
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BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with a broad range of health-related issues. Unhealthy lifestyle habits such as physical inactivity, an unhealthy diet, smoking, and alcohol consumption are hypothesized to contribute to this association. However, the lifestyle habits of individuals with OCD have been scarcely investigated. In this international survey, we explored the physical health and lifestyle habits of adults with a self-reported diagnosis of OCD. METHODS: An online global survey available in seven languages was disseminated through interest organizations and social media between July 2021 and March 2022. The survey included questions relating to socio-demographic variables and clinical characteristics (including OCD symptom severity - as measured with the 12-item self-report scale Obsessive-Compulsive Inventory [OCI-12] - and psychotropic medication), physical health, and lifestyle habits. Frequencies and percentages, or means and standard deviations, as appropriate, were calculated. Subgroup analyses by OCD symptom severity, gender, and age group were performed. RESULTS: A total of 496 individuals with OCD completed the survey and were included in the analyses (mean age = 36.0 years, SD = 12.5, range 18-79; 78.8% women). Most participants were from Europe (n = 245, 49.4%) and North America (n = 187, 37.7%). OCD symptom severity scores were on the moderate range (OCI-12 mean score = 21.2, SD = 9.1). A majority (n = 354, 71.4%) reported having comorbid somatic health issues, mainly allergies, gastrointestinal conditions, and cardiometabolic conditions. Nearly half of the sample (n = 236, 47.6%) reported a body mass index ≥ 25, corresponding to at least overweight. A significant proportion of the participants reported low physical activity (n = 271, 55.0%), unhealthy dietary habits (n = 182, 36.7%), risk consumption of alcohol (n = 111, 22.3%), and non-restorative sleep (n = 268, 54.0%). Subgroup analyses showed overall similar results across groups, with some exceptions. CONCLUSIONS: In this sample, individuals with OCD self-reported a range of health-related issues and a number of unhealthy lifestyle behaviors, most prominently a lack of physical activity. Interventions aimed at modifying unhealthy lifestyles to prevent or improve health conditions beyond the psychiatric symptoms should be considered.
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Transtorno Obsessivo-Compulsivo , Adulto , Humanos , Feminino , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Inquéritos e Questionários , Autorrelato , Hábitos , Estilo de VidaRESUMO
Current genetic research on obsessive-compulsive disorder (OCD) supports contributions to risk specifically from common single nucleotide variants (SNVs), along with rare coding SNVs and small insertion-deletions (indels). The contribution to OCD risk from large, rare copy number variants (CNVs), however, has not been formally assessed at a similar scale. Here we describe an analysis of rare CNVs called from genotype array data in 2,248 deeply phenotyped OCD cases and 3,608 unaffected controls from Sweden and Norway. We found that in general cases carry an elevated burden of large (>30kb, at least 15 probes) CNVs (OR=1.12, P=1.77×10-3). The excess rate of these CNVs in cases versus controls was around 0.07 (95% CI 0.02-0.11, P=2.58×10-3). This signal was largely driven by CNVs overlapping protein-coding regions (OR=1.19, P=3.08×10-4), particularly deletions impacting loss-of-function intolerant genes (pLI>0.995, OR=4.12, P=2.54×10-5). We did not identify any specific locus where CNV burden was associated with OCD case status at genome-wide significance, but we noted non-random recurrence of CNV deletions in cases (permutation P = 2.60×10-3). In cases where sufficient clinical data were available (n=1612) we found that carriers of neurodevelopmental duplications were more likely to have comorbid autism (P<0.001), and that carriers of deletions overlapping neurodevelopmental genes had lower treatment response (P=0.02). The results demonstrate a contribution of large, rare CNVs to OCD risk, and suggest that studies of rare coding variation in OCD would have increased power to identify risk genes if this class of variation were incorporated into formal tests.
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OBJECTIVE: To estimate the risk of all cause and cause specific mortality in people with obsessive-compulsive disorder (OCD) compared with matched unaffected people from the general population and with their unaffected siblings. DESIGN: Population based matched cohort and sibling cohort study. SETTING: Register linkage in Sweden. PARTICIPANTS: Population based cohort including 61 378 people with OCD and 613 780 unaffected people matched (1:10) on sex, birth year, and county of residence; sibling cohort consisting of 34 085 people with OCD and 47 874 unaffected full siblings. Cohorts were followed up for a median time of 8.1 years during the period from 1 January 1973 to 31 December 2020. MAIN OUTCOME MEASURES: All cause and cause specific mortality. RESULTS: 4787 people with OCD and 30 619 unaffected people died during the study period (crude mortality rate 8.1 and 5.1 per 1000 person years, respectively). In stratified Cox proportional hazards models adjusted for birth year, sex, county, migrant status (born in Sweden versus abroad), and sociodemographic variables (latest recorded education, civil status, and family income), people with OCD had an increased risk of all cause mortality (hazard ratio 1.82, 95% confidence interval 1.76 to 1.89) and mortality due to natural causes (1.31, 1.27 to 1.37) and unnatural causes (3.30, 3.05 to 3.57). Among the natural causes of death, those due to endocrine, nutritional, and metabolic diseases, mental and behavioural disorders, and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems were higher in the OCD cohort. Conversely, the risk of death due to neoplasms was lower in the OCD cohort compared with the unaffected cohort. Among the unnatural causes, suicide showed the highest hazard ratio, followed by accidents. The results were robust to adjustment for psychiatric comorbidities and familial confounding. CONCLUSIONS: Non-communicable diseases and external causes of death, including suicides and accidents, were major contributors to the risk of mortality in people with OCD. Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD.
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Transtorno Obsessivo-Compulsivo , Suicídio , Feminino , Humanos , Estudos de Coortes , Irmãos , Causas de Morte , Fatores de Risco , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Suécia/epidemiologiaRESUMO
Importance: Hypochondriasis, also known as health anxiety disorder, is a prevalent, yet underdiagnosed psychiatric disorder characterized by persistent preoccupation about having serious and progressive physical disorders. The risk of mortality among individuals with hypochondriasis is unknown. Objective: To investigate all-cause and cause-specific mortality among a large cohort of individuals with hypochondriasis. Design, Setting, and Participants: This Swedish nationwide matched-cohort study included 4129 individuals with a validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of hypochondriasis assigned between January 1, 1997, and December 31, 2020, and 41â¯290 demographically matched individuals without hypochondriasis. Individuals with diagnoses of dysmorphophobia (body dysmorphic disorder) assigned during the same period were excluded from the cohort. Statistical analyses were conducted between May 5 and September 27, 2023. Exposure: Validated ICD-10 diagnoses of hypochondriasis in the National Patient Register. Main Outcome and Measures: All-cause and cause-specific mortality in the Cause of Death Register. Covariates included birth year, sex, county of residence, country of birth (Sweden vs abroad), latest recorded education, civil status, family income, and lifetime psychiatric comorbidities. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs of all-cause and cause-specific mortality. Results: Of the 4129 individuals with hypochondriasis (2342 women [56.7%]; median age at first diagnosis, 34.5 years [IQR, 26.3-46.1 years]) and 41â¯290 demographically matched individuals without hypochondriasis (23â¯420 women [56.7%]; median age at matching, 34.5 years [IQR, 26.4-46.2 years]) in the study, 268 individuals with hypochondriasis and 1761 individuals without hypochondriasis died during the study period, corresponding to crude mortality rates of 8.5 and 5.5 per 1000 person-years, respectively. In models adjusted for sociodemographic variables, an increased rate of all-cause mortality was observed among individuals with hypochondriasis compared with individuals without hypochondriasis (HR, 1.69; 95% CI, 1.47-1.93). An increased rate was observed for both natural (HR, 1.60; 95% CI, 1.38-1.85) and unnatural (HR, 2.43; 95% CI, 1.61-3.68) causes of death. Most deaths from unnatural causes were attributed to suicide (HR, 4.14; 95% CI, 2.44-7.03). The results were generally robust to additional adjustment for lifetime psychiatric disorders. Conclusions and Relevance: This cohort study suggests that individuals with hypochondriasis have an increased risk of death from both natural and unnatural causes, particularly suicide, compared with individuals from the general population without hypochondriasis. Improved detection and access to evidence-based care should be prioritized.
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Hipocondríase , Suicídio , Humanos , Feminino , Estudos de Coortes , Causas de Morte , Suicídio/psicologia , Renda , Suécia/epidemiologiaRESUMO
INTRODUCTION: Individual cognitive behavioural therapy (CBT) with exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD). However, individual CBT is costly and time-consuming, requiring weekly therapy sessions for 3-4 months. A 4-day intensive version of CBT for OCD delivered in group format has been recently developed in Norway (Bergen 4-day treatment, B4DT). B4DT has shown promising results in several uncontrolled and one small, randomised trial, but its non-inferiority to the gold standard treatment has not been established. METHODS AND ANALYSIS: This single-blind, randomised controlled trial including 120 patients (60 per arm) will compare B4DT to individual CBT. The primary outcome is the blind assessor-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We hypothesise that B4DT will be non-inferior to gold standard CBT 15 weeks after treatment start. The non-inferiority margin is set at four points on the Y-BOCS. Secondary outcomes include time to treatment response, cost-effectiveness, response and remission rates, drop-out rates and adverse events. ETHICS AND DISSEMINATION: This study has been approved by the Swedish Ethical Review Authority. Hypotheses were specified and analysis code published before data collection started. Results from all analyses will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials and Consolidated Health Economic Evaluation Reporting Standards irrespective of outcome. TRIAL REGISTRATION NUMBER: NCT05608278.
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Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Adulto , Humanos , Terapia Cognitivo-Comportamental/métodos , Análise Custo-Benefício , Transtorno Obsessivo-Compulsivo/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do Tratamento , Estudos de Equivalência como AsuntoRESUMO
PURPOSE: Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data. PARTICIPANTS: MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029. FINDINGS TO DATE: Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase. FUTURE PLANS: The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.
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Transtorno do Espectro Autista , Transtorno Depressivo Maior , Adulto , Gravidez , Feminino , Humanos , Suécia , Depressão/terapia , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/diagnóstico , Ansiedade/terapia , Psicoterapia , Resultado do Tratamento , InternetRESUMO
Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Lítio/uso terapêutico , Antidepressivos/uso terapêutico , Eletroconvulsoterapia/métodos , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/genéticaRESUMO
OBJECTIVE: Exhaustion disorder is a stress-related diagnosis that was introduced in 2005 to the Swedish version of the International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10). The Karolinska Exhaustion Disorder Scale (KEDS) was developed to assess exhaustion disorder symptomatology. While the KEDS is intended to reflect a single construct and be used based on its total score, the instrument's characteristics have received limited attention. This study investigated the KEDS's psychometric and structural properties in a large clinical sample. METHODS: The study relied on data from 1,072 patients diagnosed with exhaustion disorder that were included in two clinical trials in Sweden. We investigated the dimensionality, homogeneity, and reliability of the KEDS using advanced statistical techniques, including exploratory structural equation modeling (ESEM) bifactor analysis. RESULTS: A one-factor confirmatory analytic model exhibited a poor fit, suggesting at least a degree of multidimensionality. The ESEM bifactor analysis found the general factor to explain about 72% of the common variance extracted, with an omega hierarchical coefficient of 0.680. Thus, the ESEM bifactor analysis did not clearly support the scale's essential unidimensionality. A homogeneity analysis revealed a scale-level H of only 0.296, suggesting that KEDS's total scores do not accurately rank individuals on the latent continuum assumed to underlie the measure. The KEDS's reliability was modest, signaling considerable measurement error. CONCLUSION: Findings reveal important limitations to the KEDS with possible implications for the status of exhaustion disorder as a nosological category. TRIAL REGISTRATION: This study was pre-registered on Open Science Framework (osf.io) on April 24, 2022 ( https://osf.io/p34sq/ ).
Assuntos
Classificação Internacional de Doenças , Pacientes , Humanos , Psicometria , Reprodutibilidade dos Testes , Análise de Classes LatentesRESUMO
Approximately one-fifth of new parents struggle with unwanted intrusive thoughts (UITs) about intentionally harming their child. This study evaluated the initial efficacy, feasibility and acceptability of a novel online self-guided cognitive intervention for new parents with distressing UITs. Self-recruited parents (N = 43, 93% female, age 23-43 years) of children 0-3 years reporting daily distressing and impairing UITs were randomized to the 8-week self-guided online cognitive intervention or to waiting-list. The primary outcome was change on the Parental Thoughts and Behaviour Checklist (PTBC) from baseline to week 8 (post-intervention). The PTBC and negative appraisals (mediator) were assessed at baseline, weekly, post-intervention and at the 1-month follow-up. Results showed that the intervention led to statistically significant reductions in distress and impairment associated with UITs at post-intervention (controlled between-group d = 0.99, 95% CI 0.56 to 1.43), which were maintained at the 1-month follow-up (controlled between-group d = 0.90, 95% CI 0.41 to 1.39). The intervention was deemed to be feasible and acceptable by the participants. Change in negative appraisals mediated reductions in UITs but the model was sensitive to mediator-outcome confounders. We conclude that this novel online self-guided cognitive intervention can potentially reduce the distress and impairment associated with UITs in new parents. Large-scale trials are warranted.Abbreviations: UITs: Unwanted Intrusive Thoughts PTBC: Parental Thoughts and Behaviour Checklist.