1.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
2.Three-dimensional Heterogeneity and Intrinsic Plasticity of the Projection from the Cerebellar Interposed Nucleus to the Ventral Tegmental Area.
Chen WANG ; Si-Yu WANG ; Kuang-Yi MA ; Zhao-Xiang WANG ; Fang-Xiao XU ; Zhi-Ying WU ; Yan GU ; Wei CHEN ; Ying SHEN ; Li-Da SU ; Lin ZHOU
Neuroscience Bulletin 2025;41(1):159-164
3.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
4.Characteristics of adrenal lesions in unilateral primary aldosteronism: a prospective study
Wei ZHANG ; Yi YANG ; Junlong LI ; Jiayu LI ; Yao ZHANG ; Youlin KUANG ; Weiyang HE ; Linqiang MA ; Ying SONG ; Jinbo HU ; Shumin YANG ; Qifu LI
Chinese Journal of Urology 2025;46(7):537-543
Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria:① Age is 18 to 80 years old;② The laboratory test indicators are in line with the diagnosis of primary aldosteronism;③ The auxiliary examination proved that only one side was involved;④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows:① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery;② Postoperative loss to follow-up;③ No surgical specimens were received or the surgical specimens were incomplete,making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited,and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin(HE)staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was(49.86 ± 9.80)years,the body mass index was(25.49 ± 3.40)kg/m2,the preoperative aldosterone level was 352(2012,556)pg/ml,and the direct renin concentration was 1.63(0.50,4.56)μIU/ml. The aldosterone/renin ratio was 224.9(57.1,641.6)(aldosterone concentration unit was pg/ml,renin concentration unit was μIU/ml),the minimum blood potassium concentration was 2.87(2.50,3.40)mmol/L,and the systolic blood pressure was(144.5 ± 19.5)mmHg. Among the 114 patients,105 had adrenal nodules detected by preoperative CT,of whom 2(1.75%)had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules,2 cases had no nodules,and 22 cases(19.30%)had multiple nodules detected(17 cases had 2 nodules and 5 cases had 3 nodules). Among them,12 cases(10.53%)presented as grossly visible multinodular lesions,while 10 cases(8.77%)appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules,13 had multiple CYP11B2-positive nodules,while the remaining had only one positive nodule. Among the 22 patients with multiple nodules,preoperative CT showed single nodules in 19 cases,hyperplasia in 1 case,and multiple nodules in 2 cases(9.09%). Among the 12 patients with grossly visible multinodular lesions,preoperative CT showed single nodules in 9 cases,hyperplasia in 1 case,and multiple nodules in 2 cases(16.67%).Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common,and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.
5.Characteristics of adrenal lesions in unilateral primary aldosteronism: a prospective study
Wei ZHANG ; Yi YANG ; Junlong LI ; Jiayu LI ; Yao ZHANG ; Youlin KUANG ; Weiyang HE ; Linqiang MA ; Ying SONG ; Jinbo HU ; Shumin YANG ; Qifu LI
Chinese Journal of Urology 2025;46(7):537-543
Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria:① Age is 18 to 80 years old;② The laboratory test indicators are in line with the diagnosis of primary aldosteronism;③ The auxiliary examination proved that only one side was involved;④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows:① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery;② Postoperative loss to follow-up;③ No surgical specimens were received or the surgical specimens were incomplete,making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited,and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin(HE)staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was(49.86 ± 9.80)years,the body mass index was(25.49 ± 3.40)kg/m2,the preoperative aldosterone level was 352(2012,556)pg/ml,and the direct renin concentration was 1.63(0.50,4.56)μIU/ml. The aldosterone/renin ratio was 224.9(57.1,641.6)(aldosterone concentration unit was pg/ml,renin concentration unit was μIU/ml),the minimum blood potassium concentration was 2.87(2.50,3.40)mmol/L,and the systolic blood pressure was(144.5 ± 19.5)mmHg. Among the 114 patients,105 had adrenal nodules detected by preoperative CT,of whom 2(1.75%)had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules,2 cases had no nodules,and 22 cases(19.30%)had multiple nodules detected(17 cases had 2 nodules and 5 cases had 3 nodules). Among them,12 cases(10.53%)presented as grossly visible multinodular lesions,while 10 cases(8.77%)appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules,13 had multiple CYP11B2-positive nodules,while the remaining had only one positive nodule. Among the 22 patients with multiple nodules,preoperative CT showed single nodules in 19 cases,hyperplasia in 1 case,and multiple nodules in 2 cases(9.09%). Among the 12 patients with grossly visible multinodular lesions,preoperative CT showed single nodules in 9 cases,hyperplasia in 1 case,and multiple nodules in 2 cases(16.67%).Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common,and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.
6.Application research of PGT in blocking the inheritance of novel mutations in the PKHD1 gene in autoso-mal recessive polycystic kidney disease pedigrees
Ning WANG ; Yan HAO ; Dawei CHEN ; Zhiguo ZHANG ; Dan KUANG ; Qing ZHANG ; Yiqi YING ; Zhaolian WEI ; Ping ZHOU ; Yunxia CAO
The Journal of Practical Medicine 2024;40(7):1006-1010
Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.
7.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
8.Aberrant outputs of cerebellar nuclei and targeted rescue of social deficits in an autism mouse model.
Xin-Yu CAI ; Xin-Tai WANG ; Jing-Wen GUO ; Fang-Xiao XU ; Kuang-Yi MA ; Zhao-Xiang WANG ; Yue ZHAO ; Wei XIE ; Martijn SCHONEWILLE ; Chris DE ZEEUW ; Wei CHEN ; Ying SHEN
Protein & Cell 2024;15(12):872-888
The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Animals
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Mice
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Disease Models, Animal
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Cerebellar Nuclei
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Autistic Disorder/pathology*
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Neurons/metabolism*
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Mutation
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Nerve Tissue Proteins/metabolism*
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Male
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Membrane Proteins
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Cell Adhesion Molecules, Neuronal
9.Fear of Covid-19 and Burnout Among Healthcare Providers in Malaysia: Is Resilience a Missing Link?
Siew-Mooi Ching ; Ramayah Thurasamy ; Ai Theng Cheong ; Anne Yee ; Poh Ying Ling ; Irmi Ismail Zarina ; Kai Wei Lee ; Jun Ying Ng ; Rofina Abdul Rahim ; Mohd Khairi Mohd Noor ; Chang Li Cheng ; Ahmad Iqmer Nashriq Mohd Nazan ; Hafizah Md Salleh ; Noor Hasliza Hassan
Malaysian Journal of Medicine and Health Sciences 2023;19(No.4):265-272
Introduction: During the COVID-19 pandemic, healthcare providers have been in great fear due to the high risk of
contracting COVID-19 infection at any time. This study aimed to determine the mediating role of resilience on the
relationship between fear of COVID-19 and burnout in primary care healthcare providers in Malaysia. Methods: This
was an online cross-sectional study involving 1280 healthcare providers aged 18 years and older from 30 government primary care clinics in Malaysia. We used the COVID-19 Fear Scale, the Copenhagen Burnout Inventory Scale,
and the Short Brief Resilience Scale to collect data from the respondents. Smart-PLS was used to perform mediation
analysis. Results: The mean age of the respondents was 36 years old and mean duration of working experience was
11 years. The majority of the respondents were female (82.4%) and Malays (82.3%). The study population consisted of nurses (47.4%), doctors (26%), medical assistants (11.9), healthcare assistant (7.1%), medical laboratory
technicians (6.4%) and drivers(1.3).The results show that fear of COVID-19 positively predicts burnout. According
to the results, resilience mediates the relationship between fear of COVID-19 and all the three burnout domains,
namely personal burnout (β=0.175,p<0.001), work-related burnout (β=0.175,p<0.001) and client-related burnout
(β=0.172,p<0.001). Additionally, resilience reduces the impact of COVID-19 fear on the three domains of burnout.
Conclusion: Our study has reported a mediating effect of resilience on the relationship between fear of COVID-19
and burnout.
10.Which Severe Mental Illnesses Most Increase the Risk of Developing Dementia? Comparing the Risk of Dementia in Patients with Schizophrenia, Major Depressive Disorder and Bipolar Disorder
Wei Hung CHANG ; Chien-Chou SU ; Kao Chin CHEN ; Yin Ying HSIAO ; Po See CHEN ; Yen Kuang YANG
Clinical Psychopharmacology and Neuroscience 2023;21(3):478-487
Objective:
Previous studies have shown that certain severe mental illnesses (SMIs) increase the risk of dementia, but those that increase the risk to a greater degree in comparison with other SMIs are unknown. Furthermore, physical illnesses may alter the risk of developing dementia, but these cannot be well-controlled.
Methods:
Using the Taiwan National Health Insurance Research Database, patients with schizophrenia, bipolar disorder and major depressive disorder (MDD) were recruited. We also recruited normal healthy subjects as the control group.All subjects were aged over 60 years, and the duration of follow-up was from 2008 to 2015. Multiple confounders were adjusted, including physical illnesses and other variables. Use of medications, especially benzodiazepines, was analyzed in a sensitivity analysis.
Results:
36,029 subjects (MDD: 23,371, bipolar disorder: 4,883, schizophrenia: 7,775) and 108,084 control subjects were recruited after matching according to age and sex. The results showed that bipolar disorder had the highest hazard ratio (HR) (HR: 2.14, 95% confidence interval [CI]: 1.99−2.30), followed by schizophrenia (HR: 2.06, 95% CI: 1.93−2.19) and MDD (HR: 1.60, 95% CI: 1.51−1.69). The results remained robust after adjusting for covariates, and sensitivity analysis showed similar results. Anxiolytics use did not increase the risk of dementia in any of the three groups of SMI patients.
Conclusion
SMIs increase the risk of dementia, and among them, bipolar disorder confers the greatest risk of developing dementia. Anxiolytics may not increase the risk of developing dementia in patients with an SMI, but still need to be used with caution in clinical practices.


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