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BACKGROUND: The association between childhood trauma (CT) and psychotic-like experiences (PLEs) is well-established. Many previous studies have recognized wisdom as a protective factor for mental health, but its role in the relation between CT and PLEs remains unknown. We aimed to investigate the mediating effect of wisdom in the above association among Chinese college students. METHODS: We conducted a nationwide survey covering 9 colleges across China and recruited a total of 5873 students using online questionnaires between September 14 and October 18, 2021. Convenience sampling was adopted. We employed the San Diego Wisdom Scale (SD-WISE), the Childhood Trauma Questionnaire (CTQ-28), and the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-15) to measure the wisdom, CT and PLEs, respectively. Descriptive, correlation, and mediation analysis were utilized. RESULTS: The positive correlation between CT and PLEs was well-replicated among college students (Pearson's r = 0.30, p < 0.001). Wisdom was negatively associated with CT (Pearson's r = - 0.46, p < 0.001) and frequency of PLEs (Pearson's r = - 0.25, p < 0.001). Total wisdom scores partially mediated the relationship between cumulative childhood trauma, neglect, abuse and PLEs, separately. The mediated model respectively explained 21.9%, 42.54% and 18.27% of the effect of CT on PLEs. Our model further suggested that childhood trauma could be related to PLEs through decreasing the following wisdom components: decisiveness, emotional regulation and prosocial behavior. CONCLUSION: For the first time, our results suggested that impaired wisdom played a role in the translation from childhood adversity to subclinical psychotic symptoms, implicating wisdom as a possible target for early intervention for psychosis among young individuals. Longitudinal work is warranted to verify the clinical implications.
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Experiências Adversas da Infância , Transtornos Psicóticos , Criança , Humanos , Estudos Transversais , Transtornos Psicóticos/psicologia , Estudantes/psicologia , Inquéritos e Questionários , China/epidemiologiaRESUMO
BACKGROUND: To investigate new lncRNAs as molecular markers of T2D. METHODS: We used microarrays to identify differentially expressed lncRNAs and mRNAs from five patients with T2D and paired controls. Through bioinformatics analysis, qRT-PCR validation, ELISA, and receiver operating characteristic (ROC) curve analysis of 100 patients with T2D and 100 controls to evaluate the correlation between lncRNAs and T2D, and whether lncRNAs could be used in the diagnosis of T2D patients. RESULTS: We identified 68 and 74 differentially expressed lncRNAs and mRNAs, respectively. The top five upregulated lncRNAs are ENST00000381108.3, ENST00000515544.1, ENST00000539543.1, ENST00000508174.1, and ENST00000564527.1, and the top five downregulated lncRNAs are TCONS_00017539, ENST00000430816.1, ENST00000533203.1, ENST00000609522.1, and ENST00000417079.1. The top five upregulated mRNAs are Q59H50, CYP27A1, DNASE1L3, GRIP2, and lnc-TMEM18-12, and the top five downregulated mRNAs are GSTM4, PODN, GLYATL2, ZNF772, and CLTC. Examination of lncRNA-mRNA interaction pairs indicated that the target gene of lncRNA XR_108954.2 is E2F2. Multiple linear regression analysis showed that XR_108954.2 (r = 0.387, p < 0.01) and E2F2 (r = 0.368, p < 0.01) expression levels were positively correlated with glucose metabolism indicators. Moreover, E2F2 was positively correlated with lipid metabolism indicators (r = 0.333, p < 0.05). The area under the ROC curve was 0.704 (95% CI: 0.578-0.830, p = 0.05) for lncRNA XR_108954.2 and 0.653 (95% CI: 0.516-0.790, p = 0.035) for E2F2. CONCLUSIONS: This transcriptome analysis explored the aberrantly expressed lncRNAs and identified E2F2 and lncRNA XR_108954.2 as potential biomarkers for patients with T2D.
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Diabetes Mellitus Tipo 2 , RNA Longo não Codificante , Biomarcadores , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Perfilação da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genéticaRESUMO
Pathophysiological and atrophic changes in the cerebellum have been well-documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural-functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum-thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum-thalamus, and contributes to the dysfunctional cerebellar-cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.
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Cerebelo , Córtex Cerebral , Substância Cinzenta , Rede Nervosa , Neuroimagem/métodos , Esquizofrenia , Tálamo , Adulto , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cerebelo/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Conectoma , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Tálamo/fisiopatologiaRESUMO
BACKGROUND: Schizophrenia is a severe mental disease with high morbidity and heritability. The SLC39A8 gene is located in 4q24 and encodes a protein that transports many metal ions. Multiple previous studies found that one of the most pleiotropic single nucleotide polymorphisms (SNPs) in SLC39A8, rs13107325, is associated with schizophrenia in the European population. However, the polymorphism of this locus is rare in other populations. In China, the Han Chinese and the Uygur Chinese are two ethnic populations that originate from different races. METHODS: A case-control study was conducted with 983 schizophrenia cases and 1230 healthy controls of the Chinese Uygur population. To validate the most promising SNP, meta-analyses were conducted with the Han Chinese and the European PGC2 data sets reported previously. RESULTS: A susceptible locus, rs10014145 (pallele = 0.014, pallele = 0.098 after correction; pgenotype = 0.004, pgenotype = 0.032 after correction) was identified in case-control study of the Chinese Uygur population. Further, the association between rs10014145 and schizophrenia was supported by a meta-analysis of Han and Uygur Chinese samples (pooled OR [95% CI] =1.10 [1.03-1.17], Z = 2.73, p = 0.006). The association between rs10014145 and schizophrenia was not significant in a meta-analysis of combined Chinese and European samples (pooled OR [95% CI] =1.07 [1.00-1.14], Z = 1.88, and p = 0.06). In addition, the "CCAC" haplotype of rs4698844-rs233814-rs13114343-rs151394 was significantly associated with schizophrenia in Uygur Chinese (P = 0.003, corrected p = 0.012). CONCLUSIONS: The results of this study support that SLC39A8 is a susceptible gene for schizophrenia in the populations of Han Chinese and Uygur Chinese in China, further studies are suggested to validate the association.
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Povo Asiático/psicologia , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença/genética , Esquizofrenia/genética , Adulto , Povo Asiático/estatística & dados numéricos , Estudos de Casos e Controles , China , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
BACKGROUND: Schizophrenia (SCZ) is a common mental disorder with high heritability, and genetic factors play a major role in the pathogenesis. Recent researches indicated that the CACNA1I involved in calcium channels probably affect the potential pathogenesis of SCZ. RESULTS: In this study, we attempted to investigate whether the CACNA1I gene contributes the risk to SCZ in the Uighur Chinese population, and performed a case-control study involving 985 patient samples and 1218 normal controls to analyze nine SNPs within the CACNA1I gene. Among these sites, six SNPs were significantly associated with SCZ in the allele distribution: rs132575 (adjusted Pallele = 0.039, OR = 1.159), rs713860 (adjusted Pallele = 0.039, OR = 0.792), rs738168 (adjusted Pallele = 0.039, OR = 0.785), rs136805 (adjusted Pallele = 0.014, OR = 1.212), rs5757760 (adjusted Pallele = 0.042, OR = 0.873) and rs5750871 (adjusted Pallele = 0.039, OR = 0.859). In addition, two SNPs turned to be risk factors for SCZ not only in the allele distribution, but also in the genotype distribution: rs132575 (adjusted Pgenotype = 0.037) and rs136805 (adjusted Pgenotype = 0.037). CONCLUSIONS: Overall, the present study provided evidence that significant association exists between the CACNA1I gene and SCZ in the Uighur Chinese population, subsequent validation of functional analysis and genetic association studies are needed to further extend this study.
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Povo Asiático/genética , Canais de Cálcio Tipo T/genética , Esquizofrenia/etnologia , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Schizophrenia (SCZ) is a common and severe mental disorder, its etiology has not been elucidated completely. In one previous genome-wide association study (GWAS) of SCZ in the Caucasian population, the QPCT has been reported as susceptible gene for SCZ. The QPCT gene encodes Glutaminyl cyclase (QC), an enzyme which is involved in the post translational modification by converting N-terminal glutamate of protein to pyroglutamate, which is resistant to protease degradation, more hydrophobic, and prone to aggregation and neurotoxic. To further investigate the role of this gene in the pathogenesis of schizophrenia in the Han Chinese population, we conducted this study in 1,248 (Mean age ± S.D, 36.44 years ± 9.0) SCZ cases, 1,248 (Mean age ± S.D, 30.62 years ± 11.35) healthy control samples for a case control study. We genotyped six SNPs in this study, including one positive SNP of the previous study, using the Sequenom MassARRAY platform. We found that rs2373000 was significantly associated with SCZ before correction [rs2373000: P allele = 0.016, χ(2) = 5.784, OR [95%CI] = 0.861 [0.762-0.972], P genotype = 0.018, χ(2) = 0.069]. After permutation correction for multiple testing, rs2373000 [rs2373000: P Allele corrected = 0.063, P genotype corrected = 0.069] showed marginal association with SCZ. Additionally, one pathogenic haplotype (TGT) containing rs2373000 was also significantly associated with SCZ. Our results are consistent with the findings of previous study and the genetic risk of QPCT gene for SCZ also exists in the Han Chinese population.
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Aminoaciltransferases/genética , Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, which codes for subunit alpha-1C of the Cav1.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder. AIMS: To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population. METHOD: We carried out a case-control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPs in the CACNA1C gene were genotyped in all samples. RESULTS: We found that rs1006737 was associated with both schizophrenia (P(allele) = 0.0014, P(genotype) = 0.006, odds ratio (OR) = 1.384, 95% CI 1.134-1.690) and major depressive disorder (P(allele) = 0.0007, P(genotype) = 0.003, OR = 1.425, 95% CI 1.160-1.752). CONCLUSIONS: Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.
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Povo Asiático/genética , Canais de Cálcio Tipo L/genética , Transtorno Depressivo Maior/genética , Esquizofrenia/genética , Adulto , Animais , Povo Asiático/psicologia , Estudos de Casos e Controles , China , Interpretação Estatística de Dados , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Camundongos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
GRM8 is a schizophrenia candidate gene that is also thought to be involved in the glutamate pathway, which is very important in the pathogenesis of schizophrenia. In this study, we aim to investigate the association between GRM8 and schizophrenia in the Uygur Chinese population. Rs2237748 and rs2299472, located in the GRM8 gene, were selected for genotyping in a set of Uygur Chinese case-control samples, which included 723 cases and 561 controls, using TaqMan assays and capillary sequencing. The statistical analysis was carried out using the online software program SHEsis, and a meta-analysis was carried out to identify other relevant studies using Review Manager 5. We found that the rs2299472 genotype was significantly associated with schizophrenia (P = 0.015, P = 0.030, after Bonferroni correction). The frequency of the CC genotype was higher in the schizophrenic patients (P = 0.008), and the frequency of the AC genotype was lower (P = 0.008). Furthermore, the meta-analysis incorporating the previous and current studies also showed that rs2299472 is associated with schizophrenia. This study indicates that the GRM8 gene may play an important role in the pathogenesis of schizophrenia.
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Povo Asiático/genética , Polimorfismo de Nucleotídeo Único , Receptores de Glutamato Metabotrópico/genética , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Etnicidade , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/etnologiaRESUMO
Purpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.
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Purpose: This meta-analysis intended to evaluate the safety and metabolic effects of the combination of olanzapine (OLZ) and samidorphan (SAM) in the treatment of schizophrenia (SCZ) patients. Patients and Methods: We searched for the English and Chinese databases for randomized controlled trials (RCTs) on the OLZ combined with SAM for SCZ. The English databases included PubMed, Web of Science, EMbase, and Cochrane Library, however, Chinese databases included Chinese Biology Medicine (CBM), VIP, Wanfang, and China National Knowledge Infrastructure (CNKI). All database searches were due by May 31, 2023. Using Review Manager 5.4 software, a meta-analysis was conducted following a literature review and data extraction. Results: This study included five RCTs involving 1781 patients. Regarding safety, the meta-analysis revealed that the probability of weight gain was reduced in the OLZ and SAM group than in the OLZ group (RR = 0.83, 95% CI (0.69, 0.99), P < 0.05). Statistically, the incidence of severe adverse safety events, dry mouth, headache, drowsiness, death, and suicidal perception events was insignificant (P > 0.05); in terms of metabolism, compared with the OLZ group, the OLZ plus SAM group reduced total cholesterol (TC) levels (MD = -3.58, 95% CI (-6.81, -0.34), P < 0.05). However, it had no significant effect on metabolic indices, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, and insulin index (P > 0.05). Conclusion: In patients with SCZ, treatment with the combination of OLZ and SAM decreased the incidence of weight gain adverse events and TC levels; nevertheless, it did not affect other adverse events or metabolic parameters. These findings provide clinicians with evidence-based guidance and support for drug selection. However, it is crucial to confirm these findings through further high-quality research.
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Major depressive disorder (MDD) with diabetes mellitus (DM) significantly reduces the quality of the patient's life, and currently, there is no effective treatment. This study explored the feasibility of Glucagon-like peptide-1 (GLP-1) in treating MDD combined with DM. The protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG) were assessed. HT22 cells were cultured with CORT + HG to construct a cell model of MDD combined with DM. Cell viability and cell apoptosis/necrocytosis were detected by CCK-8 assay and flow cytometry/confocal laser scanning microscopy, respectively, after treatment with GLP-1. In addition, BDNF and neurotransmitter levels, lactic dehydrogenase (LDH) and glucose levels, and proteins of cAMP-CREB-BDNF signal pathway in the culture supernatants were measured through an enzyme-linked immunosorbent assay and colorimetric assays and Western blot, respectively. The ideal intervention combination to construct a cell model of MDD combined with DM was CORT 200 µM and HG 50 mM for 48 h. After treatment of 50 nM GLP-1 for 48 h, the model+50 nM GLP-1 group's apoptosis and necrocytosis rates and LDH and glucose concentrations in the culture supernatants decreased significantly compared with the model group. However, the BDNF, 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), PKA, p-CREB, and p-Trkb concentrations in the culture supernatants increased significantly. GLP-1 functioned against CORT + HG-induced toxicity by activating the cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cells.
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Introduction: The childhood experiences of being overprotected and overcontrolled by family members have been suggested to be potentially traumatic. However, the possible associated factors of these experiences among young people are still not well studied. This study aimed to partly fill such gaps by a relatively large, nationwide survey of Chinese university students. Methods: A total of 5,823 university students across nine different provinces in China were included by the convenience sampling method in the data analyses. All participants completed the overprotection/overcontrol (OP/OC) subscale in a recently developed 33-item childhood trauma questionnaire (CTQ- 33). Data were also collected on all participants' socio-demographic profiles and characterization of mental health. Binary logistic regression was conducted to investigate the associated socio-demographic and psychological factors of OP/ OC. Results: The prevalence of childhood OP/OC was estimated as 15.63% (910/5,823) based on a cutoff OP/OC subscale score of ≥ 13. Binary logistic regression suggested that being male, being a single child, having depression, having psychotic-like experiences, lower family functioning, and lower psychological resilience were independently associated with childhood OP/OC experiences (all corrected-p < 0.05). The OP/OC was also positively associated with all the other trauma subtypes (abuses and neglects) in the CTQ-33, while there are both shared and unique associated factors between the OP/OC and other trauma subtypes. Post-hoc analyses suggested that OP/OC experiences were associated with depression in only females and associated with anxiety in only males. Discussion: Our results may provide initial evidence that childhood OP/OC experiences would have negative effects on young people's mental health which merits further investigations, especially in clinical populations.
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Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, -20.0; 160 mg, -19.9) vs. placebo (-14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.
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Transtorno Depressivo Maior , Adulto , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Antidepressivos/efeitos adversos , China , Método Duplo-Cego , Resultado do TratamentoRESUMO
Adhesion G protein-coupled receptor A1 (ADGRA1) belongs to the G protein-coupled receptor (GPCR) family, and its physiological function remains largely unknown. We found that Adgra1 is highly and exclusively expressed in the brain, suggesting that Adgra1 may be involved in the regulation of neurological behaviors including anxiety, depression, learning and memory. To this end, we comprehensively analyzed the potential role of ADGRA1 in the neurobehaviors of mice by comparing Adgra1-/- and their wild-type (wt) littermates. We found that Adgra1-/- male but not female mice exhibited elevated anxiety levels in the open field, elevated plus maze, and light-dark box tests, with normal depression levels in the tail-suspension and forced-swim tests, and comparable learning and memory abilities in the Morris water maze, Y maze, fear condition, and step-down avoidance tests. Further studies showed that ADGRA1 deficiency resulted in higher dendritic branching complexity and spine density as evidenced by elevated expression levels of SYN and PSD95 in amygdalae of male mice. Finally, we found that PI3K/AKT/GSK-3ß and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice. Together, our findings reveal an important suppressive role of ADGRA1 in anxiety control and synaptic function by regulating the PI3K/AKT/GSK-3ß and MEK/ERK pathways in amygdalae of male mice, implicating a potential, therapeutic application in novel anti-anxiety drug development.
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Ansiolíticos , Fosfatidilinositol 3-Quinases , Animais , Masculino , Camundongos , Dendritos/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Psychotic-like experiences (PLEs) are subclinical psychotic symptoms in the general population which are linked to increased risks for later psychiatric disorders. Male and female adolescents were reported to experience PLEs differently, but the results were mixed in previous studies. This study aimed to investigate possible sex differences in the prevalence of adolescent PLEs using a large pooled sample. A total of 21,248 Chinese adolescents aged 11 to 19 years were included, which were drawn from five separate cross-sectional surveys undertaken between 2015 to 2021 in China. PLEs were measured by the 8-item Community Assessment of Psychic Experiences. Using binary logistic regression analyses, no significant sex differences were found in the overall prevalence of PLEs after controlling for age and dataset effects. As for specific PLE subtypes, however, being female was associated with a higher prevalence of delusion of reference and a lower prevalence of visual hallucinations. Furthermore, post-hoc subgroup analyses showed that the sex differences in visual hallucinations persist across both early (<= 14 years old) and late (> 14 years old) adolescence, while differences in the delusion of reference were significant in only early adolescence. These findings may help us to further understand the biological basis of PLEs.
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Transtornos Mentais , Transtornos Psicóticos , Humanos , Adolescente , Feminino , Masculino , Prevalência , Estudos Transversais , Caracteres Sexuais , Transtornos Mentais/epidemiologia , Transtornos Psicóticos/psicologia , Alucinações/psicologia , Inquéritos e QuestionáriosRESUMO
Genomic studies on schizophrenia (SCZ) have revealed several candidate genes involved in excitatory synapse function and plasticity associated with its etiology. SHANK2 is a postsynaptic scaffolding protein, which anchors a protein complex connecting NMDAR, AMPAR, and mGluR receptors at excitatory neuronal synapses. Mutations in the SHANK2 gene have been reported to be associated with human autism spectrum disorders (ASDs) and SCZ. To identify variants in the SHANK2 gene and determine the association of SHANK2 with SCZ in the Chinese Uygur population, we conducted targeted sequencing of whole exon regions and exon-intron boundaries of SHANK2 in 1574 SCZ patients and 1481 healthy controls. A total of 149 variants were identified, including six common variants and 143 rare variants. For common variants, rs62622853 and rs3924047 showed allelic significance with SCZ before correction, but the association was eliminated after Bonferroni correction. Seven rare nonsynonymous variants, p.Arg739Trp, p.Pro807Leu, p.Ile854Phe, p.Thr1322Ser, p.Leu1434Arg, p.Val1486Ile, and p.Thr1674Met, occurred only in the patients but not in any of the healthy controls. In silico analysis predicted that p.Arg739Trp, p.Leu1434Arg, and p.Val1486Ile variants are likely to be damaging. The present study suggests that individuals with two novel rare nonsynonymous variants (p.Arg739Trp, p.Leu1434Arg) and p.Val1486Ile variants of SHANK2 might increase the susceptibility to developing SCZ disorder.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , China/epidemiologia , Simulação por Computador , Sequência Conservada , Europa (Continente)/etnologia , Éxons/genética , Ásia Oriental/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Íntrons/genética , Masculino , Mamíferos/genética , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Esquizofrenia/etnologia , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: The aim of this study was to investigate the correlation between polymorphisms in the FTO gene and TSH level in Uyghur patients with type 2 diabetes in the Xinjiang region. Material and Methods. This cohort was made up of 498 Uyghur patients with type 2 diabetes who underwent genotype screening for rs8050136 and rs9939609 using the Sequenom MassARRAY system. The distribution frequencies of the genotypes and alleles at rs8050136 and rs993960 were compared between two patient groups, those with TSH < 2.5 mU/L and those with TSH ≥ 2.5 mU/L group. We further evaluated the relationships between these different genotypes and FT3, FT4, TSH, FPG, and HbA1c expression. RESULTS: The results suggested the TSH level was 2.281 times higher in rs8050136 CC+CA carriers than in AA genotype (95%CI = 1.024~5.080, P = 0.044) and was 2.417 times higher in rs9939609 TT+TA carriers than in AA genotype (95%CI = 1.257~4.649, P = 0.008) after adjusting for age, sex, and BMI under the recessive model. TSH levels were significantly different between T2DM patients with different FTO genotypes, rs8050136 (P = 0.008) and rs9939609 (P = 0.003), with TSH levels in rs8050136 CC genotype carriers showing a significant increase compared to those in the AA genotype carriers (P = 0.005). Additionally, rs9939609 TT and TA genotype carriers had a significant increase in the TSH level when compared to AA genotype carriers (P = 0.001 and P = 0.031, respectively). The TSH level was also significantly different in these male patients with different genotypes of rs8050136 (P = 0.026) and rs9939609 (P = 0.019). And TSH levels in rs8050136 CC genotype male carriers showing a significant increase compared to those in the AA genotype carriers (P = 0.013) and rs9939609 TT genotype male carriers had a significant increase in TSH level when compared to AA genotype carriers (P = 0.004). CONCLUSION: The polymorphisms at rs8050136 and rs9939609 are associated with changes in the TSH level with rs8050136 CC and rs9939609 TT genotypes identified as potential risk factors for increased TSH levels in these male patients.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Tireotropina/sangue , Adulto , Alelos , Povo Asiático , Índice de Massa Corporal , China/epidemiologia , China/etnologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Hemoglobinas Glicadas/genética , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: The correlation between single nucleotide polymorphism (SNP) rs12807809 in Neurogranin (NRGN) gene and Schizophrenia (SCZ) was investigated by several studies, whereas the results were conflicting. Thus, we performed the present meta-analysis to combine and analyze the available studies in order to provide a more accurate result on the association of rs12807809 polymorphism in NRGN gene and SCZ vulnerability. METHODS: A comprehensive retrieval in PubMed, EMBASE, Web of Science, Cochrane Library and Wanfang was performed for relevant studies on the relationship of rs12807809 polymorphism and SCZ. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant and recessive model to appraise the association. RESULTS: The meta-analysis included 8 studies containing 12552 SCZ cases and 34783 controls. The results showed a statistically significant correlation between SCZ and rs12807809 polymorphism in overall population in allelic model (ORâ=â1.10, 95%CI 1.04-1.17). However, subgroup analysis indicated the association only existed in Caucasians but not Asian. CONCLUSION: The results of present meta-analysis suggested significant association between SNP rs12807809 in NRGN gene and SCZ susceptibility in Caucasians but not Asians.
Assuntos
Neurogranina/genética , Esquizofrenia/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: Schizophrenia is one of the most severe mental disorders and its etiology is supposed to be an interaction between genes and environmental factors. Previous genome-wide association studies of schizophrenia have reported multiple susceptibility loci including rs6704641 in the SATB2 gene. Recently, this locus was further confirmed as a genome-wide significant locus for association with schizophrenia by trans-ancestry meta-analysis of Han Chinese and Caucasian samples. However, there is no report of genetic analysis in Uygur Chinese population, which is considered to have a combined genetic background between eastern Asia and Caucasian. This study is aimed to explore whether SATB2 gene is significantly associated with schizophrenia in Uygur Chinese population, thus providing additional evidence for elucidating the role of SATB2 gene in schizophrenia. PARTICIPANTS AND METHODS: In this study, we performed a case-control analysis focusing on seven tag single nucleotide polymorphisms located in SATB2 gene among 985 patients with schizophrenia and 1218 healthy controls recruited from the Xinjiang Province of China. RESULTS: We found that rs6704641 was significantly associated with schizophrenia in both allelic and genotypic distributions (Pallele = 0.008, Pgenotype = 0.028 after correction). In addition, rs16831466 is significantly associated with schizophrenia in allelic distributions (corrected Pallele = 0.041). Besides, several haplotypes of single nucleotide polymorphism are significantly associated with schizophrenia too. CONCLUSION: Our results suggest that SATB2 is also a susceptibility gene for schizophrenia in Uygur Chinese population, and subsequent functional experiments are necessary to reveal its role in the pathogenesis.
Assuntos
Etnicidade/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas de Ligação à Região de Interação com a Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Transcrição/genética , Adulto , Povo Asiático/genética , Feminino , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , MasculinoRESUMO
Neuroimaging studies have suggested the presence of abnormalities in the prefrontal-thalamic-cerebellar circuit in schizophrenia (SCH) and depression (DEP). However, the common and distinct structural and causal connectivity abnormalities in this circuit between the two disorders are still unclear. In the current study, structural and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 20 patients with SCH, 20 depressive patients and 20 healthy controls (HC). Voxel-based morphometry analysis was first used to assess gray matter volume (GMV). Granger causality analysis, seeded at regions with altered GMVs, was subsequently conducted. To discover the differences between the groups, ANCOVA and post hoc tests were performed. Then, the relationships between the structural changes, causal connectivity and clinical variables were investigated. Finally, a leave-one-out resampling method was implemented to test the consistency. Statistical analyses showed the GMV and causal connectivity changes in the prefrontal-thalamic-cerebellar circuit. Compared with HC, both SCH and DEP exhibited decreased GMV in middle frontal gyrus (MFG), and a lower GMV in MFG and medial prefrontal cortex (MPFC) in SCH than DEP. Compared with HC, both patient groups showed increased causal flow from the right cerebellum to the MPFC (common causal connectivity abnormalities). And distinct causal connectivity abnormalities (increased causal connectivity from the left thalamus to the MPFC in SCH than HC and DEP, and increased causal connectivity from the right cerebellum to the left thalamus in DEP than HC and SCH). In addition, the structural deficits in the MPFC and its causal connectivity from the cerebellum were associated with the negative symptom severity in SCH. This study found common/distinct structural deficits and aberrant causal connectivity patterns in the prefrontal-thalamic-cerebellar circuit in SCH and DEP, which may provide a potential direction for understanding the convergent and divergent psychiatric pathological mechanisms between SCH and DEP. Furthermore, concomitant structural and causal connectivity deficits in the MPFC may jointly contribute to the negative symptoms of SCH.