Rôle du facteur de transcription PITX1 dans les pathogenèses de l'ostéoporose et des maladies parodontales

L’ostéoporose est une maladie caractérisée par une faible masse osseuse et une détérioration du tissu osseux. Cette condition entraîne une plus grande fragilité osseuse et des risques de fractures. Plusieurs études ont associé l’ostéoporose à la faible densité osseuse des mandibules, à la perte d’attache parodontale, à l’augmentation de la hauteur de la crête alvéolaire et à la chute des dents. Cette étude vise à comprendre les mécanismes sous-jacents cette perte osseuse. En effet, au cours du développement des souris, PITX1 joue un rôle clé dans l'identité des membres postérieurs et dans le bon développement des mandibules et des dents. Son inactivation complète chez la souris mène à un phénotype squelettique sévère. Tandis que, son inactivation partielle provoque des symptômes apparentés à l'arthrose avec une augmentation de la masse osseuse au niveau de l’os cortical et de l’os trabéculaire. Inversement, une étude antérieure chez des jumelles monozygotiques discordantes pour l’ostéoporose, montrent une augmentation d’environ 8.6 fois du niveau d’expression du gène Pitx1 chez la jumelle ostéoporotique. Collectivement, ces données nous ont poussés à investiguer sur le rôle du facteur de transcription PITX1 dans le métabolisme osseux normal et pathologique. Dans ce contexte, des souris transgéniques Col1α1-Pitx1 sur-exprimant Pitx1 spécifiquement dans le tissu osseux sous le promoteur du collagène de type-I (fragment 2.1kpb) ont été générées et phénotypiquement caractérisées. Ces résultats ont révelé que les souris transgéniques Col1α1-Pitx1 présentaient un phénotype similaire à celui des patients ostéoporotiques accompagné d'une perte de dents et des problèmes dentaires et parodontaux. De plus, cette étude a révélé que la surexpression de Pitx1 induit une altération de l’homéostasie osseuse via l’inactivation de la voie de signalisation Wnt/β-caténine canonique. Cette hypothèse a été appuyée par le fait que le traitement des souris transgéniques Col1α1-Pitx1 avec du chlorure de lithium, un activateur de la voie Wnt canonique, prévient le phénotype ostéoporotique chez ces souris. Finalement, cette étude établit un rôle crucial de PITX1 dans la régulation de la masse osseuse et une implication possible dans l’ostéoporose et les maladies parodontales via l’inactivation de la voie de signalisation Wnt/β-caténine canonique.Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and density leading to an increased risk of fracture. Several studies have linked osteoporosis to the low bone density of the mandibles, the periodontal attachment loss, increasing of the alveolar crest heigh and tooth loss. This study aims to understand the mechanisms underlying bone loss. During mouse development, PITX1 plays a key role in the identity of the hindlimb and the proper development of the jaws and teeth. Interestingly, PITX1-null mice displayed severe skeletal phenotype. Whereas, ageing PITX1+/- progressively developed OA-like lesions in cartilage associated with a drastic increase in cortical and trabecular bone formation. Conversely, expression analysis of osteoblasts derived from monozygotic twins discordant for osteoporosis reported an 8.6-fold up-regulation of Pitx1 expression in osteoblasts from osteoporotic twins when compared with healthy ones. Collectively, these data prompted us to investigate the role of PITX1 in normal and pathological bone metabolism. In this context, transgenic Col1α1-Pitx1 mice over expressing Pitx1 specifically in bone tissue under the type-I collagen promoter (2.3kb fragment) were generated and phenotypically characterized. These data suggested that Pitx1 overexpression induces an osteoporosis like phenotype accompanied with oral bone loss, edentulousness, dental and periodontal problems. These results suggested that Pitx1 overexpression induces alteration of bone homeostasis via the inactivating of the the Wnt/β-catenin canonical pathway. This hypothesis was supported by the fact that treatment with lithium chloride, a Wnt canonical activator, rescued the phenotype. Finally, this study establishes a crucial role of PITX1 in the regulation of bone mass and a possible involvement in the developpement of osteoporosis and periodontal disease via the inactivation of the Wnt/β-catenin canonical pathway

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization’s World Mental Health Survey Initiative

Background:There is a substantial proportion of patients who drop out of treatment beforethey receive minimally adequate care. They tend to have worse health outcomes than thosewho complete treatment. Our main goal is to describe the frequency and determinants ofdropout from treatment for mental disorders in low-, middle-, and high-income countries.Methods: Respondents from 13 low- or middle-income countries (N= 60 224) and 15 in high-income countries (N= 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for thosewho screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. Results: Dropout rates are high, both in high-income (30%) and low/middle-income (45%)countries. Dropout mostly occurs during the first two visits. It is higher in general medicalrather than in specialist settings (nearly 60%v.20% in lower income settings). It is also higherfor mild and moderate than for severe presentations. The lack of financial protection for men-tal health services is associated with overall increased dropout from care.Conclusions:Extending financial protection and coverage for mental disorders may reducedropout. Efficiency can be improved by managing the milder clinical presentations at theentry point to the mental health system, providing adequate training, support and specialistsupervision for non-specialists, and streamlining referral to psychiatrists for more severe casesPeer ReviewedPostprint (author's final draft

findings from the World Health Organization World Mental Health surveys

Funding Information: The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline and Bristol-Myers Squibb. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork and consultation on data analysis. The Argentina survey—Estudio Argentino de Epidemiología en Salud Mental (EASM)— was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204–3. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The ESEMeD surveys were funded by the European Commission (contracts QLG5–1999-01042; SANCO 2004123 and EAHC 20081308), the Piedmont Region, Italy, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000– 158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP) and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through the United Nations Development Group Iraq Trust Fund (UNDG ITF). The Lebanese Evaluation of the Burden of Ailments and Needs of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481–01), anonymous private donations to IDRAAC, Lebanon and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H), with supplemental support from the PanAmerican Health Organization (PAHO). Te Rau Hinengaro: the New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria) and the Federal Ministry of Health, Abuja, Nigeria. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology (FCT) and Ministry of Health. The Romania WMH study projects ‘Policies in Mental Health Area’ and ‘National Study regarding Mental Health and Services Use’ were carried out by the National School of Public Health and Health Services Management (former National Institute for Research and Development in Health, present National School of Public Health Management and Professional Development, Bucharest), with technical support of Metro Media Transilvania, the National Institute of Statistics—National Centre for Training in Statistics, SC. Cheyenne Services SRL, Statistics Netherlands and were funded by the Ministry of Public Health (former Ministry of Health) with supplemental support of Eli Lilly Romania SRL. The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; grant 044708) and the John W. Alden Trust. None of the funders had any role in the design, analysis, interpretation of results or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organizations, agencies or governments. J.J.M. received the John Cade Fellowship APP1056929 from the National Health and Medical Research Council and the Niels Bohr Professorship from the Danish National Research Foundation. A complete list of all within-country and cross-national WMH publications can be found at http://www.hcp.med. harvard.edu/wmh/. Publisher Copyright: © 2017 Society for the Study of AddictionBackground and aims: Prior research has found bidirectional associations between psychotic experiences (PEs) and selected substance use disorders. We aimed to extend this research by examining the bidirectional association between PEs and various types of substance use (SU) and substance use disorders (SUDs), and the influence of antecedent mental disorders on these associations. Design, setting, participants and measurements: We used data from the World Health Organization World Mental Health surveys. A total of 30 902 adult respondents across 18 countries were assessed for (a) six types of life-time PEs, (b) a range of types of SU and DSM-IV SUDs and (c) mental disorders using the Composite International Diagnostic Interview. Discrete-time survival analyses based on retrospective age-at-onset reports examined the bidirectional associations between PEs and SU/SUDs controlling for antecedent mental disorders. Findings: After adjusting for demographics, comorbid SU/SUDs and antecedent mental disorders, those with prior alcohol use disorders [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2–2.0], extra-medical prescription drug use (OR = 1.5, 95% CI = 1.1–1.9), alcohol use (OR = 1.4, 95% CI = 1.1–1.7) and tobacco use (OR = 1.3, 95% CI = 1.0–1.8) had increased odds of subsequent first onset of PEs. In contrast, those with temporally prior PEs had increased odds of subsequent onset of tobacco use (OR = 1.5, 95% CI = 1.2–1.9), alcohol use (OR = 1.3, 95% CI = 1.1–1.6) or cannabis use (OR = 1.3, 95% CI = 1.0–1.5) as well as of all substance use disorders (ORs ranged between 1.4 and 1.5). There was a dose response relationship between both count and frequency of PEs and increased subsequent odds of selected SU/SUDs. Conclusions: Associations between psychotic experiences (PEs) and substance use/substance use disorders (SU/SUDs) are often bidirectional, but not all types of SU/SUDs are associated with PEs. These findings suggest that it is important to be aware of the presence of PEs within those with SUDs or at risk of SUDs, given the plausibility that they may each impact upon the other.publishersversionpublishe

Association of Cohort and Individual Substance Use With Risk of Transitioning to Drug Use, Drug Use Disorder, and Remission From Disorder: Findings From the World Mental Health Surveys

Importance: Limited empirical research has examined the extent to which cohort-level prevalence of substance use is associated with the onset of drug use and transitioning into greater involvement with drug use. Objective: To use cross-national data to examine time-space variation in cohort-level drug use to assess its associations with onset and transitions across stages of drug use, abuse, dependence, and remission. Design, Setting, and Participants: The World Health Organization World Mental Health Surveys carried out cross-sectional general population surveys in 25 countries using a consistent research protocol and assessment instrument. Adults from representative household samples were interviewed face-to-face in the community in relation to drug use disorders. The surveys were conducted between 2001 and 2015. Data analysis was performed from July 2017 to July 2018. Main Outcomes and Measures: Data on timing of onset of lifetime drug use, DSM-IV drug use disorders, and remission from these disorders was assessed using the Composite International Diagnostic Interview. Associations of cohort-level alcohol prevalence and drug use prevalence were examined as factors associated with these transitions. Results: Among the 90 027 respondents (48.1% [SE, 0.2%] men; mean [SE] age, 42.1 [0.1] years), 1 in 4 (24.8% [SE, 0.2%]) reported either illicit drug use or extramedical use of prescription drugs at some point in their lifetime, but with substantial time-space variation in this prevalence. Among users, 9.1% (SE, 0.2%) met lifetime criteria for abuse, and 5.0% (SE, 0.2%) met criteria for dependence. Individuals who used 2 or more drugs had an increased risk of both abuse (odds ratio, 5.17 [95% CI, 4.66-5.73]; P \u3c .001) and dependence (odds ratio, 5.99 [95% CI, 5.02-7.16]; P \u3c .001) and reduced probability of remission from abuse (odds ratio, 0.86 [95% CI, 0.76-0.98]; P = .02). Birth cohort prevalence of drug use was also significantly associated with both initiation and illicit drug use transitions; for example, after controlling for individuals’ experience of substance use and demographics, for each additional 10% of an individual’s cohort using alcohol, a person’s odds of initiating drug use increased by 28% (odds ratio, 1.28 [95% CI, 1.26-1.31]). Each 10% increase in a cohort’s use of drug increased individual risk by 12% (1.12 [95% CI, 1.11-1.14]). Conclusions and Relevance: Birth cohort substance use is associated with drug use involvement beyond the outcomes of individual histories of alcohol and other drug use. This has important implications for understanding pathways into and out of problematic drug use

Perceived helpfulness of treatment for posttraumatic stress disorder: Findings from the World Mental Health Surveys

Background: Perceived helpfulness of treatment is an important healthcare quality indicator in the era of patient-centered care. We examine probability and predictors of two key components of this indicator for posttraumatic stress disorder (PTSD). Methods: Data come from World Mental Health surveys in 16 countries. Respondents who ever sought PTSD treatment (n = 779) were asked if treatment was ever helpful and, if so, the number of professionals they had to see to obtain helpful treatment. Patients whose treatment was never helpful were asked how many professionals they saw. Parallel survival models were estimated for obtaining helpful treatment in a specific encounter and persisting in help-seeking after earlier unhelpful encounters. Results: Fifty seven percent of patients eventually received helpful treatment, but survival analysis suggests that it would have been 85.7% if all patients had persisted in help-seeking with up to six professionals after earlier unhelpful treatment. Survival analysis suggests that only 23.6% of patients would persist to that extent. Odds of ever receiving helpful treatment were positively associated with receiving treatment from a mental health professional, short delays in initiating help-seeking after onset, absence of prior comorbid anxiety disorders and childhood adversities, and initiating treatment before 2000. Some of these variables predicted helpfulness of specific treatment encounters and others predicted persistence after earlier unhelpful encounters. Conclusions: The great majority of patients with PTSD would receive treatment they considered helpful if they persisted in help-seeking after initial unhelpful encounters, but most patients whose initial treatment is unhelpful give up before receiving helpful treatment

a World Mental Health Surveys report

Funding Information: The WHO World Mental Health Survey collaborators are Sergio Aguilar-Gaxiola, MD, PhD; Ali Al-Hamzawi, MD; Mohammed Salih Al-Kaisy, MD; Jordi Alonso, MD, PhD; Yasmin A. Altwaijri, PhD; Laura Helena Andrade, MD, PhD; Lukoye Atwoli, MD, PhD; Corina Benjet, PhD; Guilherme Borges, ScD; Evelyn J. Bromet, PhD; Ronny Bruffaerts, PhD; Brendan Bunting, PhD; Jose Miguel Caldas-de-Almeida, MD, PhD; Gra?a Cardoso, MD, PhD; Somnath Chatterji, MD; Alfredo H. Cia, MD; Louisa Degenhardt, PhD; Koen Demyttenaere, MD, PhD; Silvia Florescu, MD, PhD; Giovanni de Girolamo, MD; Oye Gureje, MD, DSc, FRCPsych; Josep Maria Haro, MD, PhD; Meredith G. Harris, PhD; Hristo Hinkov, MD, PhD; Chi-yi Hu, MD, PhD; Peter de Jonge, PhD; Aimee Nasser Karam, PhD; Elie G. Karam, MD; Norito Kawakami, MD, DMSc; Ronald C. Kessler, PhD; Andrzej Kiejna, MD, PhD; Viviane Kovess-Masfety, MD, PhD; Sing Lee, MBBS; Jean-Pierre Lepine, MD; John J. McGrath, MD, PhD; Maria Elena Medina-Mora, PhD; Zeina Mneimneh, PhD; Jacek Moskalewicz, PhD; Fernando Navarro-Mateu, MD, PhD; Marina Piazza, MPH, ScD; Jose Posada-Villa, MD; Kate M. Scott, PhD; Tim Slade, PhD; Juan Carlos Stagnaro, MD, PhD; Dan J. Stein, FRCPC, PhD; Margreet ten Have, PhD; Yolanda Torres, MPH, Dra.HC; Maria Carmen Viana, MD, PhD; Daniel V. Vigo, MD, DrPH; Harvey Whiteford, MBBS, PhD; David R. Williams, MPH, PhD; Bogdan Wojtyniak, ScD. Funding Information: The Argentina survey -- Estudio Argentino de Epidemiología en Salud Mental (EASM) -- was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación) - (Grant Number 2002–17270/13–5). The 2007 Australian National Survey of Mental Health and Wellbeing is funded by the Australian Government Department of Health and Ageing. The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204–3. The Bulgarian Epidemiological Study of common mental disorders EPIBUL is supported by the Ministry of Health and the National Center for Public Health Protection. EPIBUL 2, conducted in 2016–17, is supported by the Ministry of Health and European Economic Area Grants. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The Mental Health Study Medellín – Colombia was carried out and supported jointly by the Center for Excellence on Research in Mental Health (CES University) and the Secretary of Health of Medellín. The ESEMeD project is funded by the European Commission (Contracts QLG5–1999-01042; SANCO 2004123, and EAHC 20081308), (the Piedmont Region (Italy)), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000–158-CE), Generalitat de Catalunya (2017 SGR 452; 2014 SGR 748), Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through United Nations Development Group Iraq Trust Fund (UNDG ITF). The Israel National Health Survey is funded by the Ministry of Health with support from the Israel National Institute for Health Policy and Health Services Research and the National Insurance Institute of Israel. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013, H25-SEISHIN-IPPAN-006) from the Japan Ministry of Health, Labour and Welfare. The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481–01), anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H), with supplemental support from the Pan American Health Organization (PAHO). Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council, and the Health Research Council. The Northern Ireland Study of Mental Health was funded by the Health & Social Care Research & Development Division of the Public Health Agency. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Polish project Epidemiology of Mental Health and Access to Care –EZOP Project (PL 0256) was carried out by the Institute of Psychiatry and Neurology in Warsaw in consortium with Department of Psychiatry - Medical University in Wroclaw and National Institute of Public Health-National Institute of Hygiene in Warsaw and in partnership with Psykiatrist Institut Vinderen–Universitet, Oslo. The project was funded by the European Economic Area Financial Mechanism and the Norwegian Financial Mechanism. EZOP project was co-financed by the Polish Ministry of Health. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology (FCT) and Ministry of Health. The Saudi National Mental Health Survey (SNMHS) is conducted by the King Salman Center for Disability Research. It is funded by Saudi Basic Industries Corporation (SABIC), King Abdulaziz City for Science and Technology (KACST), Ministry of Health (Saudi Arabia), and King Saud University. Funding in-kind was provided by King Faisal Specialist Hospital and Research Center, and the Ministry of Economy and Planning, General Authority for Statistics. The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUS-Murcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia. The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Funding Information: The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline, and Bristol-Myers Squibb. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork, and consultation on data analysis. None of the funders had any role in the design, analysis, interpretation of results, or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organizations, agencies, or governments. Funding Information: In the past 3 years, RCK reports being a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. FNM reports non-financial support from Otsuka outside and not related to the submitted work. In the past 3 years LD has received untied educational grant funding from Indivior and Seqirus, not related to the submitted work. DJS has received research grants and/or honoraria from Lundbeck, Johnson & Johnson, Servier and Takeda. The remaining authors declare that they have no competing interests. Publisher Copyright: © 2021, The Author(s).Background: Treatment guidelines for generalized anxiety disorder (GAD) are based on a relatively small number of randomized controlled trials and do not consider patient-centered perceptions of treatment helpfulness. We investigated the prevalence and predictors of patient-reported treatment helpfulness for DSM-5 GAD and its two main treatment pathways: encounter-level treatment helpfulness and persistence in help-seeking after prior unhelpful treatment. Methods: Data came from community epidemiologic surveys in 23 countries in the WHO World Mental Health surveys. DSM-5 GAD was assessed with the fully structured WHO Composite International Diagnostic Interview Version 3.0. Respondents with a history of GAD were asked whether they ever received treatment and, if so, whether they ever considered this treatment helpful. Number of professionals seen before obtaining helpful treatment was also assessed. Parallel survival models estimated probability and predictors of a given treatment being perceived as helpful and of persisting in help-seeking after prior unhelpful treatment. Results: The overall prevalence rate of GAD was 4.5%, with lower prevalence in low/middle-income countries (2.8%) than high-income countries (5.3%); 34.6% of respondents with lifetime GAD reported ever obtaining treatment for their GAD, with lower proportions in low/middle-income countries (19.2%) than high-income countries (38.4%); 3) 70% of those who received treatment perceived the treatment to be helpful, with prevalence comparable in low/middle-income countries and high-income countries. Survival analysis suggested that virtually all patients would have obtained helpful treatment if they had persisted in help-seeking with up to 10 professionals. However, we estimated that only 29.7% of patients would have persisted that long. Obtaining helpful treatment at the person-level was associated with treatment type, comorbid panic/agoraphobia, and childhood adversities, but most of these predictors were important because they predicted persistence rather than encounter-level treatment helpfulness. Conclusions: The majority of individuals with GAD do not receive treatment. Most of those who receive treatment regard it as helpful, but receiving helpful treatment typically requires persistence in help-seeking. Future research should focus on ensuring that helpfulness is included as part of the evaluation. Clinicians need to emphasize the importance of persistence to patients beginning treatment.publishersversionpublishe

Age of onset and cumulative risk of mental disorders:a cross-national analysis of population surveys from 29 countries

Background: Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk. Methods: In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account. Findings: We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9–29·2) for male respondents and 29·8% (29·2–30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9–47·8) for male respondents and 53·1% (51·9–54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14–32) for male respondents and 20 years (12–36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents. Interpretation: By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course. Funding: None.</p

Patterns and correlates of patient-reported helpfulness of treatment for common mental and substance use disorders in the WHO World Mental Health Surveys

Patient-reported helpfulness of treatment is an important indicator of quality in patient-centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post-traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys - 17 in high-income countries (HICs) and 13 in low- and middle-income countries (LMICs) - carried out as part of the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of individuals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help-seeking if earlier treatments are not helpful