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SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

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Zoological research 2024年第4期45卷 845-856页

作者： Qunxian Wang Yanshuang Jiang Zijun Meng Xiangjun Dong Dongjie Hu Liangye Ji Weihui Zhou Weihong Song Chongqing Key Laboratory of child neurodevelopment and Cognitive Disorders Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400000China Second Affiliated Hospital and Yuying children’s Hospital Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains *** this study,the role of SIL1 in APP processing was explored both in vitro and in *** the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant *** the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type *** blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant *** indicated that SIL1 expression decreased in APP23/PS45 *** of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in ***,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 ***,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 ***,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 *** findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

关键词： Alzheimer’s disease SIL1 APP processing Cognitive impairment

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NLRP3 inflammasome as a novel therapeutic target for Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2098-2099页

作者： Yun Zhang Zhifang Dong Weihong Song Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina

In a recent publication in Nature,Ising et *** the effect of the NLRP3 inflammasome on Aβ-induced tau pathology in Alzheimer’s disease(AD).The findings indicate that NLRP3 may be a novel target for the treatment of AD.

关键词： Alzheimer Aβ tau

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MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models

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Signal Transduction and Targeted Therapy 2019年第1期4卷 149-160页

作者： Yehong Du Yexiang Du Yun Zhang Zhilin Huang Min Fu Junjie Li Yayan Pang Peng Lei Yu Tian Wang Weihong Song Guiqiong He Zhifang Dong Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing400014PR China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing400016PR China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBCV6T 1Z3Canada West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu610041SichuanChina Brain research Centre The University of British ColumbiaVancouverBCV6T 2B5Canada

Mitogen-activated protein kinase(MAPK)phosphatase 1(MKP-1)is an essential negative regulator of MAPKs by dephosphorylating MAPKs at both tyrosine and threonine *** of the MAPK signaling pathway has been associated with Alzheimer’s disease(AD).However,the role of MKP-1 in AD pathogenesis remains ***,we report that MKP-1 levels were decreased in the brain tissues of patients with AD and an AD mouse *** reduction in MKP-1 gene expression appeared to be a result of transcriptional inhibition via transcription factor specificity protein 1(Sp1)cis-acting binding elements in the MKP-1 gene ***-β(Aβ)-induced Sp1 activation decreased MKP-1 ***,upregulation of MKP-1 inhibited the expression of both Aβprecursor protein(APP)andβ-site APP-cleaving enzyme 1 by inactivating the extracellular signal-regulated kinase 1/2(ERK)/MAPK signaling ***,upregulation of MKP-1 reduced Aβproduction and plaque formation and improved hippocampal long-term potentiation(LTP)and cognitive deficits in APP/PS1 transgenic *** results demonstrate that MKP-1 impairment facilitates the pathogenesis of AD,whereas upregulation of MKP-1 plays a neuroprotective role to reduce Alzheimer-related ***,this study suggests that MKP-1 is a novel molecule for AD treatment.

关键词： Alzheimer Aβ impairment

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Effects of remote support courses on parental mental health and child development in autism:A randomized controlled trial

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World Journal of psychiatry 2024年第12期14卷 1892-1904页

作者： Jia-Hui Lu Hua Wei Yu Zhang Fan Fei Hai-Yan Huang Qiu-Jun Dong Jing Chen Dong-Qin Ao Li Chen Ting-Yu Li Yan Li Ying Dai Growth Development and Mental Health Center of Children and AdolescentsChildren’s Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing 401146China

BACKGROUND Sustaining the mental health of autistic children’s parents can be *** To determine the effect of remote support courses on the mental health of parents and the development of autistic *** Parents of 140 autistic children were randomly assigned to two groups receiving a 2-week intervention:The control group received caregiver-mediated intervention(CMI);the experimental group received CMI with remote family psychological support courses(R-FPSC).The Parenting Stress Index-Short Form,Parenting Sense of Competence Scale,Generalized Anxiety Disorder-7,and Patient Health Questionnaire-9 were used to measure parents’mental *** childhood Autism Rating Scale and Gesell Developmental Schedules were used to evaluate children’s *** Improved parenting stress,sense of competence,depression,and anxiety were found in both groups,but improvements in parenting stress(81.10±19.76 vs 92.10±19.26,P<0.01)and sense of competence(68.83±11.23 vs 63.91±10.86,P<0.01)were greater in the experimental group,although the experimental group showed no significant reduction in depression or ***’s development did not differ significantly between the groups at follow-up;however,experimental group parents exhibited a short-term increase in training enthusiasm(12.78±3.16 vs 11.57±3.15,P<0.05).CONCLUSION Integrating R-FPSC with CMI may be effective in reducing parenting stress,enhancing parents’sense of competence,and increasing parents'training enthusiasm.

关键词： Autism spectrum disorder Parenting stress Parenting sense of competence Caregiver-mediated intervention Family psychological intervention

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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study

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Neural Regeneration research 2022年第7期17卷 1582-1587页

作者： Xiaoyue Li Xuan Mo Tao Liu Robin Shao Kayla Teopiz Roger S.McIntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Laboratory of Emotion and Cognition The Affiliated Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Department of psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Canadian Rapid Treatment Center of Excellence MississaugaONCanada Mood Disorders Psychopharmacology unit Poul Hansen Family Centre for DepressionUniversityHealth NetworkTorontoONCanada Department of psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoONCanada Ministry of Education joint international research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive *** preclinical models of neurological and psychiatric diseases,Lycium barbarum polysaccharide(LBP)extracted from Goji berries had antidepressant effects including but not limited to anti-oxidative and anti-inflammatory ***,the effect of LBP on subthreshold depression is *** investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents,we conducted a randomized,double-blind,placebo-controlled trial(RCT)with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical *** participants were randomly assigned to groups where they received either 300 mg LBP(LBP group,n=15,3 boys and 12 girls aged 15.13±2.17 years)or a placebo(placebo group,n=14,2 boys and 12 girls aged 15±1.71 years)for 6 successive *** analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale(HAMD-24)scores relative to the baseline and a higher remission rate(HAMD-24 total score≤7)at 6 weeks compared with the placebo *** on the Beck Depression Inventory-II(BDI-II),Pittsburgh Sleep Quality Index(PSQI),Kessler Psychological Distress Scale(Kessler),and Screen for child Anxiety-Related Emotional Disorders(SCARED)were similar between the LBP and placebo *** side effects related to the intervention were reported in either *** results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold ***,LBP was well tolerated with no treatment-limiting adverse *** trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold *** study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University(Guangzho

关键词： adolescents efficacy Goji berry Lycium barbarum polysaccharide randomized clinical trial safety subthreshold depression tolerance

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Epidemiological characteristics of childhood migraine syndrome in Serbia

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Neural Regeneration research 2011年第9期6卷 692-698页

作者： Marija Knezevi-Poganev Neboja Jovi Vesna Iveti Danka Filipovi Dragan Katani Institute of child and Youth Health Care of Vojvodina Clinic of Neurology and psychiatry for children and Youth Medical Faculty of Novi Sad Institute for PhysiologyDepartment for Neurophysiology

This study investigated childhood migraine, examining the clinical characteristics of different childhood migraine types, predisposing factors, and possible medical treatments in a sample of children in Serbia. This was the first epidemiological study in Serbia using the operational diagnostic criteria of the international Headache Society. The present study examined 30 636 children between 1988 and 2006, including 15 434 （50.38%） males and 15 202 （49.62%） females, in nine towns in Vojvodina, a northern province in Serbia. Migraine was reported in 2 644 （8.63%） children aged 3 to 7 years, consisting of 1 189 （8.0%） males and 1 455 （9.6%） females. Migraine with aura accounted for 25.55%, migraine without aura for 67.21% and other migraine syndromes for 7.23% of reported migraine sufferers. The mean age of first migraine attack across groups was 5 years and 1.8 months. Migraine with aura was associated with an earlier onset than migraine without aura Migraine was more frequent among younger groups of children who were breastfed for a shorter period of time. child healthcare in Vojvodina has a high level of specialization, with more than half of the children reporting migraine diagnosed and treated by neuropediatricians. Socioeconomic status, duration of breastfeeding, birth order, and age of entering full-day nursery care were found to be important factors for childhood migraine. These findings suggest that healthcare providers should educate parents about these predisposing factors, so they can be identified and avoided early.

关键词： children migraine epidemiology health care Serbia

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Epidemiology of anorexia nervosa in a French community-based sample of 39,542 adolescents

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Open Journal of Epidemiology 2013年第2期3卷 53-61页

作者： Nathalie T. Godart Stéphane Legleye Caroline Huas Sylvana M. Coté Marie Choquet Bruno Falissard Evelyne Touchette Department of General Practice University of Tours Tours France école de Psychologie Université Laval Quebec City Canada Institut National des études Démographiques (INED) Paris France international Laboratory for child and Adolescent Mental Health (unit 669 INSERM Paris France and Research Unit on Chil- dren’s Psychosocial Maladjustment University of Montreal Montreal Canada) psychiatry Institut Mutualiste Montsouris Paris France unit 669 INSERM University of Paris-Sud and University of Paris Descartes UMR-S0669 Paris France

Purpose: To assess the prevalence of DSM-IV anorexia nervosa criteria, anorexia nervosa and subthreshold subgroups, and their incidence between the ages of 12 and 17 years using Cole’s international thinness cut-offs, and to characterize these anorexic adolescents by parental socioeconomic status and whether or not they reported receiving treatment. Method: In all, a representative sample of 39,542 French adolescents (19,658 girls and 19,884 boys) was recruited in a cross-sectional study in 2008. Anorexia nervosa DSM-IV diagnosis was determined by a self-administered questionnaire. Results: Among females, 0.5% (n = 105) met criteria for anorexia nervosa between the ages of 12 and 17 years, whereas among males, the prevalence was 0.03% (n = 6). In females, the prevalence of sub-threshold anorexia nervosa was found to be between 1.2% (n = 216) and 3.3% (n = 618);more than 75% were of the restrictive subtype. The highest incidence of anorexia nervosa was at 16 years. There was also a greater prevalence of sub-threshold anorexia nervosa subgroups among subjects with high parental socioeconomic status. More than half of the female adolescents who met the anorexia nervosa criteria reported receiving treatment for their disorder, versus 23% to 40% of the adolescents in the sub-threshold subgroups (P sample of adolescents. Using Cole’s international thinness cut-off could improve international comparability among studies. Adolescents from the higher socioeconomic categories were more likely to be anorexic.

关键词： Anorexia Nervosa Prevalence Incidence Adolescence Community Survey

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A comparison of perinatal and infant mortality rates in British Columbia and Finland:Similarities and differences

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Open Journal of Pediatrics 2013年第1期3卷 35-41页

作者： Paivi Rautava Anne Synnes Jennifer Claydon Jaakko Matomaki Mika Gissler Turku Clinical research Centre Turku University HospitalTurkuFinland British Columbia’s Women’s Hospital VancouverCanada Pediatric research unit Department of PediatricsTurku University HospitalTurkuFinland Faculty of Medicine Centre for Child PsychiatryUniversity of TurkuTurkuFinland National Institute for Health and Welfare HelsinkiFinland

Introduction: Despite similarities, perinatal and infant mortality rates between British Columbia, (BC) Canada and Finland differ. Key variables that may influence stillbirth, early neonatal, perinatal and infant mortality rates in BC and Finland were studied. Methods: After standardizing definitions, data for all births between 2001 and 2009 from provincial and national registries were used to compare perinatal outcomes between BC and Finland. Annual change was evaluated with regression analyses. Results: Births before 22 weeks gestation were excluded. All mortality rates per 1000 were lower in Finland vs BC (perinatal: 5.1 vs 6.2, stillbirth: 3.4 vs 3.9, early neonatal 1.7 vs 2.4, infant 2.9 vs 4.0;all p Higher multiple birth and preterm birth rates in BC are affecting mortality rates. Finland’s policy of single embryo transfer is a potential explanation. It is possible to have good perinatal outcomes and low caesarean section rates. Conclusions: The Finnish health care system may suggest possible solutions for improved perinatal outcomes. Lower per capita health care expenditures in Finland do not appear to have adversely affected perinatal outcomes.

关键词： Perinatal Mortality Infant Mortality international Comparative Studies

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More anxious than depressed:prevalence and correlates in a 15-nation study of anxiety disorders in people with type 2 diabetes mellitus

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General psychiatry 2019年第4期32卷 197-205页

作者： Santosh K Chaturvedi Shayanth Manche Gowda Helal Uddin Ahmed Fahad D Alosaimi Nicola Andreone Alexey Bobrov Viola Bulgari Giuseppe Carra Gianluca Castelnuovo Giovanni de Girolamo Tomasz Gondek Nikola Jovanovic Thummala Kamala Andrzej Ki Nebojsa Lalic Dusica Lecic-Tosevski Fareed Minhas Victoria Mutiso David Ndetei Golam Rabbani Suntibenchakul Somruk Sathyanarayana Srikanta Rizwan Taj Umberto Valentini Olivera Vukovic Wolfgang Wolwer Larry Cimino Arie Nouwen Cathy Lloyd Norman Sartorius Department of psychiatry National Institute of Mental Health and Neuro-SciencesBangaloreIndia Institute of Mental Health BelgradeSerbia Samatvam Endocrinology Diabetes Center and Jnana Sanjeevini Diabetes Hospital and Medical Center BangaloreIndia University of Lower Silesia WroclawPoland Center for Global Mental Health RawalpindiPakistan University of Nairobi NairobiKenya Faculty of Medicine Chulalongkorn UniversityBangkokThailand Pakistan Institute of Medical Sciences IslamabadPakistan Department of psychiatry and Psychotherapy Medical FacultyUniversity of DusseldorfDusseldorfGermany ProConsult Owings MillsMarylandUSA 不详 child Adolescent and Family psychiatry National Institute of Mental HealthDhakaBangladesh Department of psychiatry King Saud UniversityRiyadhSaudi Arabia IRCCS Ospedale Sacro Cuore Don Calabria NegrarItaly National research Centre for psychiatry and Narcology MoscowRussia IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli BresciaItaly University of Milano-Bicocca BicoccaItaly Department of Psychology Catholic UniversityMilanItaly Department of psychiatry Wroclaw Medical UniversityWroclawPoland

Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. Aims To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. Methods People aged 18-65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-international Neuropsychiatric Interview. Demographic and medical record data were collected. Results A total of 3170 people with type 2 diabetes (56.2% women;with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%;however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. Conclusions Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.

关键词： type 2 diabetes mellitus anxious depressed

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