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BACKGROUND: Antipsychotic polypharmacy (APP) is frequently prescribed for schizophrenia-spectrum disorders. Despite the inconsistent findings on efficacy, APP may be beneficial for subgroups of psychotic patients. This meta-analysis of individual patient data investigated moderators of efficacy and tolerability of APP in adult patients with schizophrenia-spectrum disorders. DESIGN: We searched PubMed, EMBASE, and the Cochrane Central Register of Randomized Trials until September 1, 2022, for randomized controlled trials comparing APP with antipsychotic monotherapy. We estimated the effects with a one-stage approach for patient-level moderators and a two-stage approach for study-level moderators, using (generalized) linear mixed-effects models. Primary outcome was treatment response, defined as a reduction of 25 % or more in the Positive and Negative Syndrome Scale (PANSS) score. Secondary outcomes were study discontinuation, and changes from baseline on the PANSS total score, its positive and negative symptom subscale scores, the Clinical Global Impressions Scale (CGI), and adverse effects. RESULTS: We obtained individual patient data from 10 studies (602 patients; 31 % of all possible patients) and included 599 patients in our analysis. A higher baseline PANSS total score increased the chance of a response to APP (OR = 1.41, 95 % CI 1.02; 1.94, p = 0.037 per 10-point increase in baseline PANSS total), mainly driven by baseline positive symptoms. The same applied to changes on the PANSS positive symptom subscale and the CGI severity scale. Extrapyramidal side effects increased significantly where first and second-generation antipsychotics were co-prescribed. Study discontinuation was comparable between both treatment arms. CONCLUSIONS: APP was effective in severely psychotic patients with high baseline PANSS total scores and predominantly positive symptoms. This effect must be weighed against potential adverse effects.
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A boy, aged 7 months, presented with severe global developmental delay (GDD), refractory epilepsy, hypotonia, nystagmus, ocular hypertelorism, a broad nasal bridge, everted upper lip, a high palatal arch, and cryptorchidism. Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K) in the EEF1A2 gene, and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation. This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy, genetic testing for EEF1A2 gene mutations should be considered. This is particularly important for those exhibiting hypotonia, nonverbal communication, and craniofacial deformities, to facilitate a confirmed diagnosis.
Subject(s)
Developmental Disabilities , Peptide Elongation Factor 1 , Humans , Male , Infant , Developmental Disabilities/genetics , Peptide Elongation Factor 1/genetics , Epilepsy/genetics , Mutation , Mutation, MissenseABSTRACT
BACKGROUND: Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. METHODS: In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. RESULTS: The tendency of changes in residual symptoms was categorized into four classes: "light residual symptom decline (15.4%)", "residual symptom disappears (39.3%)", "steady residual symptom (6.3%)" and "severe residual symptom decline (39.0%)". We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms' persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. CONCLUSIONS: Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.
Subject(s)
Depressive Disorder , Humans , Longitudinal Studies , Male , Female , Adult , Middle Aged , Disease Progression , Latent Class Analysis , Medication Adherence/psychology , Severity of Illness IndexABSTRACT
RATIONALE: Depression is a prevalent psychiatric disease, and ginsenoside Rg1 is a bioactive compound extracted from the root of Panax ginseng C.A.Mey. To systematically investigate the effectiveness of Rg1 in rodent models of depression and provide evidence-based references for treating depression. METHODS: Electronic searches for rodent studies were performed from inception to October 2022, e.g., PUBMED and EMBASE. Data extraction and quality evaluation were performed for the references, and meta-analysis was performed on the selected data using Review Manager 5.3.5. The outcomes were analyzed via a random-effect model and presented as mean difference (MD) with 95% confidence intervals (CIs). RESULTS: A total of 24 studies and 678 animals were included in this meta-analysis. Rg1 remarkably improved depressive-like symptoms of depressed rodents, including the sucrose preference test (25.08, 95% CI: 20.17-30.00, Z = 10.01, P < 0.00001), forced swimming test (MD = -37.69, 95% CI: (-45.18, -30.2); Z = 9.86, P < 0.00001), and the tail suspension test (MD = -22.93, seconds, 95% CI: (-38.49, -7.37); Z = 2.89, P = 0.004). CONCLUSIONS: The main antidepressant mechanism of Rg1 was concluded to be the neurotransmitter system, oxidant stress system, and inflammation. Conclusively, this study indicated the possible protective and therapeutic effects of Rg1 for treating depression via multiple mechanisms.
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BACKGROUND: Liver cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in hepatocellular carcinoma (HCC). The Wnt/ß-catenin pathway plays a crucial role in liver cancer stemness, progression, metastasis, and drug resistance, but no clinically approved drugs have targeted this pathway efficiently so far. We aimed to elucidate the role of COLEC10 in HCC stemness. METHODS: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were employed to search for the association between COLEC10 expression and HCC stemness. Colony formation, sphere formation, side population, and limiting dilution tumor initiation assays were used to identify the regulatory role of COLEC10 overexpression in the stemness of HCC cell lines. Wnt/ß-catenin reporter assay and immunoprecipitation were performed to explore the underlying mechanism. RESULTS: COLEC10 level was negatively correlated with HCC stemness. Elevated COLEC10 led to decreased expressions of EpCAM and AFP (alpha-fetoprotein), two common markers of liver CSCs. Overexpression of COLEC10 inhibited HCC cells from forming colonies and spheres, and reduced the side population numbers in vitro, as well as the tumorigenic capacity in vivo. Mechanically, we demonstrated that overexpression of COLEC10 suppressed the activity of Wnt/ß-catenin signaling by upregulating Wnt inhibitory factor WIF1 and reducing the level of cytoplasmic ß-catenin. COLEC10 overexpression promoted the interaction of ß-catenin with the component of destruction complex CK1α. In addition, KLHL22 (Kelch Like Family Member 22), a reported E3 ligase adaptor predicted to interact with CK1α, could facilitate COLEC10 monoubiquitination and degradation. CONCLUSION: COLEC10 inhibits HCC stemness by downregulating the Wnt/ß-catenin pathway, which is a promising target for liver CSC therapy.
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AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.
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BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Carcinoma, Hepatocellular , Cell Proliferation , Ferroptosis , Gene Expression Regulation, Neoplastic , Liver Neoplasms , MicroRNAs , Neoplasm Proteins , RNA, Circular , Animals , Female , Humans , Male , Mice , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement/genetics , Disease Progression , Ferroptosis/genetics , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , MicroRNAs/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA, Circular/genetics , Xenograft Model Antitumor AssaysSubject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatic Veins , Portal Vein , Humans , Cholangiocarcinoma/diagnostic imaging , Portal Vein/diagnostic imaging , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/complications , Hepatic Veins/diagnostic imaging , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/etiology , Arteriovenous Fistula/complications , Arteriovenous Fistula/surgery , Lithiasis/surgery , Lithiasis/diagnostic imaging , Lithiasis/complications , Male , Middle Aged , Liver Diseases/diagnostic imaging , Liver Diseases/diagnosis , Liver Diseases/etiology , Diagnosis, Differential , Female , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.
Subject(s)
Lymph Node Excision , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Lymph Node Excision/methods , Male , Nasopharyngeal Neoplasms/surgery , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Carcinoma/surgery , Nasopharyngeal Carcinoma/pathology , Female , Middle Aged , Salvage Therapy/methods , Natural Orifice Endoscopic Surgery/methods , Cadaver , Adult , Pharynx/surgery , Aged , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Treatment OutcomeABSTRACT
OBJECTIVE: To identify the core residual symptom of MDD and assess its relationship with patients' long-term outcomes. METHOD: All patients were administered antidepressants during the acute phase and treated continuously. The 521 patients remitted at month 6 of a multicenter prospective project were included. Remission was defined as a Quick Inventory of Depressive Symptoms-Self-Report total score of ≤5. Functional impairments were measured with the Sheehan Disability Scale, quality of life with the Quality of Life Enjoyment and Satisfaction Questionnaire - short form, and family burden with the Family Burden Scale of Disease. Visits were scheduled at baseline, weeks 2, 8, 12, and month 6. RESULTS: Difficulty with concentration/decision making was the core residual symptom of MDD, determined with the centrality measure of network analysis. It was positively associated with functional impairments and family burden (r = 0.35, P < 0.01 and r = 0.31, P < 0.01, respectively) and negatively associated with life satisfaction (r = -0.29, P < 0.01). The exhibition of this residual symptom was associated with a family history of psychiatric disorders (OR = 2.610 [1.242-5.485]). CONCLUSIONS: The core residual symptom of MDD, difficulty with concentration/decision making, is associated with poorer social functioning, heavier family burden, and lower life satisfaction. Early detection and intervention of this symptom may be beneficial. CLINICAL TRIALS REGISTRATION NUMBER: (Chinese Clinical Trials.gov identifier) ChiCTR-OOC-17012566 and ChiCTR-INR-17012574.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/drug therapy , Quality of Life/psychology , Prospective Studies , Antidepressive Agents/therapeutic use , Self ReportABSTRACT
In this paper, the influence of an earthquake on radon exhalation rate of uranium tailings reservoir beach under high temperature environment is studied by using a self-made integrated simulation test device for natural disasters, and a scale model test based on similarity and dimensional laws. The results show that, (1)When the peak acceleration reaches 0.6g, the radon exhalation rate increases sharply with the increase of peak acceleration, and tends to be gentle after 1.0g. (2)Under the action of high temperature, the radon exhalation rate increases rapidly with the increase of high temperature time, and gradually becomes flat after the 4th hour. (3)Compared with loading the earthquake condition only, the coupling effect of high temperatures and earthquakes causes a greater degree of damage to the beach surface of a uranium tailings reservoir under the same acceleration conditions, and the fissure rate and radon exhalation rate of the beach surface are substantially increased.
Subject(s)
Earthquakes , Radiation Monitoring , Radon , Uranium , Radon/analysis , Temperature , Uranium/analysis , Exhalation , Radiation Monitoring/methodsABSTRACT
The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.
Subject(s)
Bone and Bones , Neovascularization, Physiologic , Osteogenesis , Tissue Engineering , Tissue Engineering/methods , Humans , Animals , Bone and Bones/blood supply , Bone and Bones/innervation , Bone Regeneration/drug effects , Tooth/innervation , AngiogenesisABSTRACT
Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARSCoV2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARSCoV2 N proteininduced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). The expression levels of SARSCoV2 N protein, SREBP cleavageactivating protein (SCAP), mature Nterminal SREBP2, NLRP3, procaspase1, cleaved caspase1, IL1ß and IL18 were examined by western blotting. The expression levels of SREBP2, HMGCoA reductase, HMGCS1, low density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), SREBP1c, fatty acid synthase, stearyl coenzyme A desaturase 1, acetylCoA carboxylase α and ATPcitrate lyase were determined by reverse transcriptionquantitative PCR. The translocation of SCAP or NLRP3 from the endoplasmic reticulum to the Golgi was detected by confocal microscopy. The results showed that excess PI promoted SCAPSREBP and NLRP3 complex translocation to the Golgi, potentially leading to NLRP3 inflammasome activation and lipogenic gene expression. Furthermore, PI amplified SARSCoV2 N proteininduced inflammation via the SCAPSREBP pathway, which facilitates NLRP3 inï¬ammasome assembly and activation. Inhibition of phosphate uptake with phosphonoformate sodium alleviated NLRP3 inflammasome activation and reduced SREBPmediated lipogenic gene expression in VSMCs stimulated with PI and with SARSCoV2 N protein overexpression. Inhibition of SREBP2 or small interfering RNAinduced silencing of SREBP2 effectively suppressed the effect of PI and SARSCoV2 N protein on NLRP3 inflammasome activation and lipogenic gene expression. In conclusion, the present study identified that PI amplified SARSCoV2 N proteininduced NLRP3 inflammasome activation and lipogenic gene expression via the SCAPSREBP signaling pathway.
Subject(s)
COVID-19 , Hyperphosphatemia , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Proprotein Convertase 9/metabolism , Sterol Regulatory Element Binding Protein 2/genetics , Sterol Regulatory Element Binding Protein 2/metabolism , SARS-CoV-2/metabolism , Phosphates , Sterol Regulatory Element Binding Protein 1/metabolism , Signal Transduction , InflammationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS, or Happy Feeling Powder), a typical Chinese herbal prescription, is frequently used for treating depression by the multi-level and multi-target mechanism. AIM OF THE STUDY: To systematically investigate the efficacy and safety of KXS on depression in preclinic trials. MATERIALS AND METHODS: We independently searched for preclinical animal studies of KXS on depression from inception to June 28, 2022, using electronic databases, e.g., PUBMED. The measurements were performed to assess the outcomes of behavioral tests. RESULTS: This systematic review and meta-analysis included twenty-four studies and 608 animals. A remarkable effect of KXS in depression behavioral tests, including sucrose consumption test (SMD: 2.36, 95% CI: (1.81, 2.90); Z = 8.49, P < 0.00001)., forced swimming test (MD = -60.52, 95% CI: (-89.04, -31.99); Z = 4.16, P < 0.0001), rearing times (MD=4.48, 95% CI: (3.39, 5.57); Z = 8.05, P < 0.00001) and crossing times (MD = -33.7, 95% CI: (25.74, 41.67); Z = 8.29, P < 0.00001) in the open field test, showing KXS's excellent efficiency in improving depressive-like symptoms of animals. CONCLUSIONS: Our meta-analysis showed KXS remarkably relieved animals' depressive-like symptoms, providing evidence that KXS can be a promising drug candidate for depression treatment.
Subject(s)
Depression , Drugs, Chinese Herbal , Animals , Depression/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Rodentia , Disease Models, AnimalABSTRACT
The sterol regulatory element-binding protein (SREBP) activation and cytokine level were significantly increased in coronavirus disease-19. The NLRP3 inflammasome is an amplifier for cellular inflammation. This study aimed to elucidate the modulatory effect of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP) on trimethylamine N-oxide (TMAO)-induced lipogenesis and NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). Our data indicated that SARS-CoV-2 NP activates the dissociation of the SREBP cleavage activating protein (SCAP) from the endoplasmic reticulum, resulting in SREBP activation, increased lipogenic gene expression, and NLRP3 inflammasome activation. TMAO was applied to VSMC-induced NLRP3 inflammasome by promoting the SCAP-SREBP complex endoplasmic reticulum-to-Golgi translocation, which facilitates directly binding of SARS-CoV-2 NP to the NLRP3 protein for NLRP3 inï¬ammasome assembly. SARS-CoV-2 NP amplified the TMAO-induced lipogenic gene expression and NLRP3 inflammasome. Knockdown of SCAP-SREBP2 can effectively reduce lipogenic gene expression and alleviate NLRP3 inflammasome-mediated systemic inflammation in VSMCs stimulated with TMAO and SARS-CoV-2 NP. These results reveal that SARS-CoV-2 NP amplified TMAO-induced lipogenesis and NLRP3 inflammasome activation via priming the SCAP-SREBP signaling pathway.
Subject(s)
COVID-19 , Methylamines , Sterol Regulatory Element Binding Proteins , Humans , Sterol Regulatory Element Binding Proteins/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , SARS-CoV-2 , Intracellular Signaling Peptides and Proteins/metabolism , Signal Transduction , Inflammation , Nucleocapsid ProteinsABSTRACT
BACKGROUND: There is not yet a valid and evidence-based system to classify patients with MDD into more homogeneous subtypes based on their clinical features. This study aims to identify symptom-based subtypes of MDD and investigate whether the treatment outcomes of those subtypes would be different. METHOD: The cohort was established at 12 densely populated cities of China. A total of 1487 patients were enrolled. All participants were 18-65 years old and diagnosed with MDD. Participants were followed up at baseline, weeks 4, 8, and 12, and months 4 and 6. K-means algorithm was used to cluster patients with MDD according to clinical symptoms. The network analysis was adopted to characterize and compare the symptom patterns in the clusters. We also examined the associations between the clusters and the clinical outcomes. RESULTS: The optimal number of the clusters was determined to be 2. Each cluster's maximum Jaccard Co-efficient was calculated to be >0.5 (cluster1 = 0.53, cluster 2 = 0.67). The symptom "depressed mood" and some other affective symptoms were the most prominent in cluster 1. Somatic symptoms, such as weight loss and general somatic symptoms, had the greatest expected influence in cluster 2. Compared with the response rates of the patients in the "somatic cluster", those of the patients in the "affective cluster" were significantly higher (P < 0.05). CONCLUSIONS: Patients with MDD might be classified into two symptom-based subtypes featured with affective symptoms or somatic symptoms. The treatment efficacy and prognosis of the subtype featured with somatic symptoms may be worse.
Subject(s)
Depressive Disorder, Major , Medically Unexplained Symptoms , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/therapy , Prospective Studies , Treatment Outcome , China/epidemiology , Cluster AnalysisABSTRACT
PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI). METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes. RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups. CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.
Subject(s)
Antidepressive Agents , Depressive Disorder, Treatment-Resistant , Ketamine , Suicidal Ideation , Ketamine/therapeutic use , Ketamine/administration & dosage , Ketamine/adverse effects , Humans , Depressive Disorder, Treatment-Resistant/drug therapy , Antidepressive Agents/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
Background/objective: Patients with major depressive disorder (MDD) have altered learning rates for rewards and losses in non-social learning paradigms. However, it is not well understood whether the ability to learn from social interactions is altered in MDD patients. Using reinforcement learning during the repeated Trust Game (rTG), we investigated how MDD patients learn to trust newly-met partners in MDD patients. Method: Sixty-eight MDD patients and fifty-four controls each played as investor and interacted with ten different partners. We manipulated both the level of trustworthiness by varying the chance of reciprocity (10, 30, 50, 70 and 90%) and reputation disclosure, where partners reputation was either pre-disclosed or hidden. Results: Our reinforcement learning model revealed that MDD patients had significantly higher learning rates for losses than the controls in both the reputation disclosure and non-disclosure condition. The difference was larger when reputation was not disclosed than disclosed. We observed no difference in learning rates for gains in either condition. Conclusions: Our findings highlight that abnormal learning for losses underlies the social learning process in MDD patients. This abnormality is higher when situational unpredictability is high versus low. Our findings provide novel insights into social rehabilitation of MDD. (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Depressive Disorder, Major , Social Learning , Trust , Interpersonal Relations , Reinforcement, PsychologyABSTRACT
Studies on the association between depression and self-reported endometriosis are limited, and further studies are required to investigate this association. Data were collected from the National Health and Nutrition Examination Survey database (2005-2006). Based on the inclusion and exclusion criteria, 100 participants with self-reported endometriosis and 1295 participants without self-reported endometriosis were included, representing a total population of 64,989,430. Depression severity was assessed using the Patient Health Questionnaire 9 (PHQ9). A survey-weighted logistic regression analysis was performed to explore the association between depression and endometriosis. Subgroup analyses were conducted to explore heterogeneity. The prevalence of endometriosis was 7.17%. A significant positive association was found between the PHQ9 score and endometriosis. After adjusting for all covariates, the PHQ9 score positively correlated with endometriosis. Furthermore, compared with the participants without depression, those with moderate depression were more prone to have endometriosis both in unadjusted and fully adjusted model. However, the relationship between severe depression and endometriosis was not significant in all models (P > 0.05). Our findings highlight the influence of depression on the prevalence of self-reported endometriosis. Further studies are required to elucidate the causal relationship between depression and self-reported endometriosis.