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BACKGROUND: Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia, and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are 3 first-line endogenous antioxidants. Various cognitive functions decline differently during the schizophrenia course. The characteristic roles of the 3 antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. METHODS: We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH levels; clinical symptoms; and 9 cognitive test scores were measured. RESULTS: Blood CAT levels were higher in the acute patients than in the chronic patients, whereas SOD and GSH levels were similar to one another. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function, and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better global assessment of function in the acute phase and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. CONCLUSIONS: This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH affected none. Further studies are needed to explore the underlying mechanisms.
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Antipsicóticos , Esquizofrenia , Humanos , Antioxidantes/uso terapéutico , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Cognición , Glutatión , Superóxido Dismutasa , Glutatión PeroxidasaRESUMEN
Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.
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Antidepresivos/uso terapéutico , Encéfalo/metabolismo , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/terapia , Plasticidad Neuronal , Animales , Encéfalo/fisiopatología , Ensayos Clínicos como Asunto , Trastorno Depresivo Mayor/fisiopatología , Modelos Animales de Enfermedad , Agonismo Parcial de Drogas , Terapia Electroconvulsiva , Humanos , Ketamina/administración & dosificación , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal , Transmisión Sináptica , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Resultado del TratamientoRESUMEN
A series of star-shaped multi-polar chromophores (compounds 1-3) containing functionalized quinoxaline and quinoxalinoid (indenoquinoxaline and pyridopyrazine) units has been synthesized and characterized for their two-photon absorption (2PA) properties both in the femtosecond and the nanosecond time domain. Under our experimental conditions, these model fluorophores are found to manifest strong and wide-dispersed two-photon absorption in the near-infrared region. It is demonstrated that molecular structures with multi-branched π frameworks incorporating properly functionalized quinoxalinoid units would possess large molecular nonlinear absorptivities within the studied spectral range. Effective optical-power attenuation and stabilization behaviors in the nanosecond time domain of a selected representative dye molecule (i.e., compound 2) from this model compound set were also investigated and the results indicate that such structural motif could be a useful approach for the molecular design toward strong two-photon-absorbing material systems for quick-responsive and broadband optical-suppressing-related applications, particularly to confront long laser pulses.
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BACKGROUND: The translin-associated factor X (TSNAX) gene, located adjacent to the DISC1 gene, has been implicated in schizophrenia. While cognitive impairment determines long-term the functional outcome of schizophrenia, the role of TSNAX in cognitive dysfunction of schizophrenia patients remains elusive. This study aimed to explore the genetic effect of TSNAX on cognitive functions of schizophrenia. METHODS: We recruited 286 chronic schizophrenia patients who had been stabilized with antipsychotics for at least 2 months and genotyped three TSNAX SNPs (rs1630250, rs766288, rs6662926). Clinical symptoms and seven cognitive domains were assessed. The score of cognitive tests was standardized to T score. RESULTS: Clinical symptoms were similar among genotypes of all the three SNPs. The GLM analysis demonstrated that TSNAX genetic polymorphisms influenced cognitive function of schizophrenia patients after adjustment for gender, age, and education. The patients with the rs1630250 C/G genotype performed better than the G/G homozygotes in the Trail Making A (p = 0.034). Those with the rs766288 G/T genotype also performed better than the G/G homozygotes in the Trail Making A (p = 0.012). The patients with the G/G genotype of rs6662926 also performed better than the C/C homozygotes in verbal learning and memory test (p = 0.044). CONCLUSIONS: This study suggests that the TSNAX gene variation may influence the cognitive functions of the patients with schizophrenia.
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Disfunción Cognitiva , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Genotipo , Polimorfismo de Nucleótido Simple , Cognición , Disfunción Cognitiva/genéticaRESUMEN
Dementia has become an all-important disease because the population is aging rapidly and the cost of health care associated with dementia is ever increasing. In addition to cognitive function impairment, associated behavioral and psychological symptoms of dementia (BPSD) worsen patient's quality of life and increase caregiver's burden. Alzheimer's disease is the most common type of dementia and both behavioral disturbance and cognitive impairment of Alzheimer's disease are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline in Alzheimer's disease. We review the literature regarding dementia (especially Alzheimer's disease), BPSD and relevant findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine. Literatures suggest that behavioral disturbance and cognitive impairment of Alzheimer's disease may be associated with excitatory neurotoxic effects which result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition, function, agitation/aggression and delusion in Alzheimer's disease. On the other hand, some NMDA modulators which enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic symptoms. We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological symptoms of Alzheimer's disease. Prospective study using NMDA enhancers in patients with Alzheimer's disease and associated behavioral disturbance is needed to verify this hypothesis.
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Lysozyme (Lyz) is an antimicrobial peptide, a safe adjunct, and it has been indicated that Lyz can promote vibrissae follicle growth by enhancing the hair-inductive capacity of dermal papilla cells in mice. The present study produced a new type of minoxidil (Mx)-coated antifungal Lyz-shelled microbubble (LyzMB) for inhibiting bacteria and allergies on the oily scalp. The potential of Mx-coated LyzMBs (Mx-LyzMBs) combined with ultrasound (US) and the role of LyzMB fragments in enhancing hair follicle growth were investigated. Mx grafted with LyzMBs were synthesized and the loading efficiency of Mx on cationic LyzMBs was 20.3%. The biological activity of Lyz in skin was determined using an activity assay kit and immunohistochemistry expression, and the activities in the US+Mx-LyzMBs group were 65.8 and 118.5 µU/mL at 6 and 18 h, respectively. In hair follicle cell culture experiments, the lengths of hair follicle cells were significantly enhanced in the US+Mx-LyzMBs group (108.2 ± 11.6 µm) compared to in the US+LyzMBs+Mx group (44.3 ± 9.8 µm) and the group with Mx alone (79.6 ± 12.0 µm) on day 2 (p < 0.001). During 21 days of treatment in animal experiments, the growth rates at days 10 and 14 in the US+Mx-LyzMBs group increased by 19.4 and 65.7%, respectively, and there were significant differences (p < 0.05) between the US+Mx-LyzMBs group and the other four groups. These findings indicate that 1-MHz US (applied at 3 W/cm2, acoustic pressure = 0.266 MPa) for 1 min combined with Mx-LyzMBs can significantly increase more penetration of Mx and LyzMB fragments into skin and enhance hair growth than Mx alone.
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Recent evidence indicates that enhancing N-methyl-D-aspartate (NMDA) neurotransmission with the treatment of NMDA/glycine site agonists, such as D-serine, or a glycine transporter-1 (GlyT-1) antagonist, N-methylglycine (sarcosine), can improve symptoms of schizophrenia. To compare these two novel approaches, 60 patients with chronic schizophrenia were enrolled into a 6-wk double-blind, placebo-controlled trial of add-on treatments at the reported effective dosages (2 g/d). Clinical assessments were conducted every other week. Treatment group x treatment duration interaction analysis by multiple linear regression showed that sarcosine was superior to placebo at all four outcome measures of Positive and Negative Syndrome Scale (PANSS) total (p=0.005), Scale for the Assessment of Negative Symptoms (SANS) (p=0.021), Quality of Life (QOL) (p=0.025), and Global Assessment of Functioning (GAF) (p=0.042). However, d-serine did not differ significantly from placebo in any measure. Sarcosine treatment was better than d-serine in effect sizes for all outcome measures. Sarcosine also surpassed placebo in most of the measures of five PANSS factors and five SANS subscales. All treatments were well tolerated. These findings suggest that the GlyT-1 inhibitor is more efficacious than the NMDA/glycine site agonist in treatment for schizophrenia, including life quality and global function, at the dosages tested.
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Antipsicóticos/administración & dosificación , Sarcosina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , Serina/administración & dosificación , Actividades Cotidianas , Adulto , Enfermedad Crónica , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Placebos , Calidad de Vida , Esquizofrenia/diagnóstico , EstereoisomerismoRESUMEN
Schizophrenia's pathogenesis remains elusive. Cognitive dysfunction is the endophenotype and outcome predictor of schizophrenia. The LIM and SH3 domain protein (LASP1) protein, a component of CNS synapses and dendritic spines, has been related to the N-methyl-D-aspartate receptor (NMDAR) dysfunction hypothesis and schizophrenia. A single-nucleotide polymorphism (rs979607) in the LASP1 gene promoter region has been also implicated in schizophrenia susceptibility. The aim of this study was to investigate the role of the LASP1 rs979607 polymorphism in the cognitive functions of patients with schizophrenia. Two hundred and ninety-one Han Taiwanese patients with schizophrenia were recruited. Ten cognitive tests and two clinical rating scales were assessed. The scores of cognitive tests were standardized to T-scores. The genotyping of the LASP1 rs979607 polymorphism was performed using TaqMan assay. Among the 291 patients, 85 were C/C homozygotes of rs979607, 141 C/T heterozygotes, and 65 T/T homozygotes, which fitted the Hardy-Weinberg equilibrium. After adjusting age, gender, and education with general linear model, the C/C homozygotes performed better than C/T heterozygotes in overall composite score (p = 0.023), Category Fluency test (representing processing speed and semantic memory) (p = 0.045), and Wechsler Memory Scale (WMS)-III backward Spatial Span test (p = 0.025), albeit without correction for multiple comparisons for the latter two individual tests. To the best of our knowledge, this is the first study suggesting that the genetic variation of LASP1 may be associated with global cognitive function, category verbal fluency, and spatial working memory of patients with schizophrenia. The finding also lends support to the NMDAR dysfunction hypothesis of schizophrenia. More studies with longitudinal designs are warranted.
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Proteínas Adaptadoras Transductoras de Señales/genética , Cognición , Proteínas del Citoesqueleto/genética , Predisposición Genética a la Enfermedad , Proteínas con Dominio LIM/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Adolescente , Adulto , Anciano , Pueblo Asiatico/genética , Disfunción Cognitiva , Femenino , Humanos , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Pruebas Neuropsicológicas , Regiones Promotoras Genéticas , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatología , Taiwán , Adulto JovenRESUMEN
The D-amino acid oxidase activator (DAOA, also known as G72) gene is a strong schizophrenia susceptibility gene. Higher G72 protein levels have been implicated in patients with schizophrenia. The current study aimed to differentiate patients with schizophrenia from healthy individuals using G72 single nucleotide polymorphisms (SNPs) and G72 protein levels by leveraging computational artificial intelligence and machine learning tools. A total of 149 subjects with 89 patients with schizophrenia and 60 healthy controls were recruited. Two G72 genotypes (including rs1421292 and rs2391191) and G72 protein levels were measured with the peripheral blood. We utilized three machine learning algorithms (including logistic regression, naive Bayes, and C4.5 decision tree) to build the optimal predictive model for distinguishing schizophrenia patients from healthy controls. The naive Bayes model using two factors, including G72 rs1421292 and G72 protein, appeared to be the best model for disease susceptibility (sensitivity = 0.7969, specificity = 0.9372, area under the receiver operating characteristic curve (AUC) = 0.9356). However, a model integrating G72 rs1421292 only slightly increased the discriminative power than a model with G72 protein alone (sensitivity = 0.7941, specificity = 0.9503, AUC = 0.9324). Among the three models with G72 protein alone, the naive Bayes with G72 protein alone had the best specificity (0.9503), while logistic regression with G72 protein alone was the most sensitive (0.8765). The findings remained similar after adjusting for age and gender. This study suggests that G72 protein alone, without incorporating the two G72 SNPs, may have been suitable enough to identify schizophrenia patients. We also recommend applying both naive Bayes and logistic regression models for the best specificity and sensitivity, respectively. Larger-scale studies are warranted to confirm the findings.
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OBJECTIVE: Thoracic infection and pneumonia are prevalent in patients with schizophrenia; however, it is unclear whether patients with schizophrenia are at an increased risk of developing pleural empyema. DESIGN: A retrospective cohort study with propensity-matched cohorts with and without schizophrenia. SETTING: Using the National Health Insurance Research Database of Taiwan. PARTICIPANTS: We identified 55 888 patients with schizophrenia newly diagnosed in 2000-2011 and same number of individuals without schizophrenia as the comparison cohort, frequency matched by propensity scores estimated using age, sex, occupation, income, urbanisation, year of diagnosis and comorbidities. PRIMARY OUTCOME MEASURES: We assessed incident pleural empyema by the end of 2011 and used the Cox proportional hazards model to calculate the schizophrenia cohort to comparison cohort HR of pleural empyema. RESULTS: The overall incidence of pleural empyema was 2.44-fold greater in the schizophrenia cohort than in the comparison cohort (4.39vs1.80 per 10 000 person-years), with an adjusted HR of 2.87(95% CI 2.14 to 3.84). Stratified analyses by age, sex, occupation, income, urbanisation and comorbidity revealed significant hazards for pleural empyema associated with schizophrenia in all subgroups. CONCLUSIONS: Patients with schizophrenia are at an increased risk of developing pleural empyema and require greater attention and appropriate support.
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Empiema Pleural/epidemiología , Esquizofrenia/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Empiema Pleural/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-amino acid oxidase inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for 6 weeks' add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. RESULTS: Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group. CONCLUSIONS: Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.
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Antipsicóticos/administración & dosificación , Clozapina/administración & dosificación , D-Aminoácido Oxidasa/antagonistas & inhibidores , Esquizofrenia/tratamiento farmacológico , Benzoato de Sodio/administración & dosificación , Adulto , Cognición , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Taiwán , Resultado del TratamientoRESUMEN
BACKGROUND: Population-based cohort study investigating the depression risk for patients with uterine leiomyoma (UL) is unavailable. This study investigated the subsequent risk of depression among patients with UL in an Asian population. METHODS: Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 21,168 patients diagnosed with UL between 2000 and 2010, and a non-UL cohort of 82,108 women without UL matched by age and year of diagnosis. The occurrence of depression and Cox method measured adjusted hazard ratios (aHRs) were monitored until the end of 2011. The depression risk altered by surgery was also evaluated. RESULTS: The overall incidence of depression was 54% higher in the UL cohort than in the non-UL cohort (7.48 vs. 4.88/1000 person-years, p<0.001), with an aHR of 1.46 [95% confidence interval (CI)=1.36-1.57] for the UL cohort. The depression risk increased with age and with comorbidity in both cohorts. Surgical intervention reduced the depression incidence to 4.76/1000 person-years for women with UL, with an aHR of 0.64 (95% CI=0.51-0.81) compared with those without a surgical treatment. CONCLUSION: The risk of depression is significantly higher in patients with UL than in those without UL. Surgical intervention for UL could significantly reduce the risk of depression. Evaluation of psychiatric status in patients with UL is strongly recommended.
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Depresión/epidemiología , Leiomioma/epidemiología , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Leiomioma/cirugía , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The cystine/glutamate antiporter system xc(-), playing a critical role in the regulation of glutamate release, might be implicated in the pathogenesis of schizophrenia. This study examined whether peripheral expressions of the system xc(-) subunits are characteristic of schizophrenia. METHODS: Expression of system xc(-) genes including SLC3A2 and SLC7A11 in peripheral WBCs of patients with schizophrenia and healthy individuals were measured using quantitative PCR. Both psychotropic-free and medicated patients with schizophrenia were recruited. RESULTS: A total of 96 schizophrenia patients (48 medicated and 48 drug-free) and 96 healthy individuals were enrolled. The mRNA expression levels using the 2(-ΔΔC)T Method of both SLC3A2 and SLC7A11 in WBCs of schizophrenia patients were markedly lower than that of healthy individuals (0.22 and 0.48, respectively, the mRNA expression level of normal controls was normalized to 1). There was no significant difference between medicated and drug-free patients in the mRNA expressions of both SLC3A2 and SLC7A11. The Receiver Operating Characteristics (ROC) analysis of SLC3A2 mRNA levels using ΔΔCT values for drug-free schizophrenia patients vs. healthy controls determined an optimal cutoff value, 0.801, with high sensitivity (1.000) and modest specificity (0.694) (area under curve of ROC = 0.794). CONCLUSION: This is the first study indicating that the peripheral mRNA expression levels of SLC7A11 and SLC3A2 may be lower in patients with schizophrenia than healthy individuals. The finding supports the hypo-glutamatergic neurotransmission hypothesis in schizophrenia. Whether mRNA expression of system xc(-) subunits genes, particularly SLC3A2, could serve as a potential biomarker of schizophrenia needs further studies.
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Sistema de Transporte de Aminoácidos y+/metabolismo , Cadena Pesada de la Proteína-1 Reguladora de Fusión/metabolismo , Leucocitos/metabolismo , Esquizofrenia/metabolismo , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Área Bajo la Curva , Femenino , Ácido Glutámico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Curva ROC , Esquizofrenia/tratamiento farmacológico , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Depression is prevalent in patients with chronic rhinosinusitis (CRS). However, no population-based study has ever investigated this relationship. We used nationwide population insurance data to conduct a retrospective cohort study to evaluate the subsequent risk of depression among patients with CRS. METHODS: We used the National Health Insurance Research Database (NHIRD) of Taiwan identified 15,371 CRS patients diagnosed during 2000-2010. The non-CRS group consisted of 61,484 individuals without CRS frequency matched by sex, age, and the year of diagnosis. The occurrence of depression was monitored until the end of 2011. The hazard ratios (HRs) of depression were estimated using the Cox proportional hazards model after adjusting for demographic characteristics and comorbidities. RESULTS: The overall incidence of depression was 77% higher in the CRS group than in the non-CRS group (8.25 vs. 4.66/1000 person-years, p<0.001), with an adjusted HR of 1.56 (95% confidence interval=1.43-1.70). Further data analyses revealed that the adjusted HRs of depression in the CRS group compared with the non-CRS group by sex, age, urbanization level, monthly income, occupation category, and comorbidity were all significant. However, there was no difference in incidences of depression between CRS patients with and without surgical treatment (8.31 vs. 8.24/1000 person-years). CONCLUSION: The present study suggests that patients with CRS are at an increased risk of depression, compared with those without CRS. Therefore, we should pay attention to the psychiatric status of these patients and provide adequate support for them.
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Depresión/epidemiología , Rinitis/epidemiología , Sinusitis/epidemiología , Adulto , Anciano , Enfermedad Crónica , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
The association between cholelithiasis and depression remains unclear. We examined the risk of depression in patients with cholelithiasis. From the National Health Insurance population claims data of Taiwan, we identified 14071 newly diagnosed cholelithiasis patients (4969 symptomatic and 9102 asymptomatic) from 2000 to 2010. For each cholelithiasis patient, 4 persons without cholelithiasis were randomly selected in the control cohort from the general population frequency matched by age, sex, and diagnosis year. Both cohorts were followed up until the end of 2011 to monitor the occurrence of depression. Adjusted hazard ratios (aHRs) of depression were estimated using the Cox proportional hazards model after controlling for age, sex and comorbidities. The overall incidence rates of depression were 1.87- and 1.83-fold greater in the symptomatic and asymptomatic cholelithiasis subcohorts than in the control cohort (incidence, 10.1 and 9.96 vs 5.43 per 1000 person-years, respectively). The multivariable Cox proportional hazards regression analysis revealed higher variable-specific aHRs in women than in men, in younger patients than in older patients, and in those without comorbidities than in those with any comorbidity. Cholecystectomy reduced the hazard of developing depression with aHRs of 0.79 (95% confidence interval [CI] 0.62-0.99) for symptomatic cholelithiasis patients and 0.76 (95% CI 0.60-0.96) for asymptomatic patients. Patients with cholelithiasis are at a higher risk of developing depression than the general population. Patients could be benefited from cholecystectomy and have the hazard of developing depression significantly reduced.
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Colelitiasis/psicología , Colelitiasis/cirugía , Depresión/epidemiología , Adulto , Anciano , Enfermedades Asintomáticas , Colelitiasis/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Modelos de Riesgos Proporcionales , Taiwán/epidemiología , Adulto JovenRESUMEN
The prevalence of Alzheimer's disease (AD) in the elderly is growing rapidly worldwide, and the deteriorating clinical course of AD places a heavy burden on both the patients and their families. Early detection and intervention of mild cognitive impairment in the early phase of AD is vital for the purpose of improving the cognitive performance of patients and preventing the existing deficits from worsening. However, the main compounds currently used to treat early AD, acetylcholinesterase inhibitors (AChEIs), are unsatisfactory in efficacy and safety. Moreover, evidence indicates that AChEIs are ineffective in treating AD at extremely early stages, which implies that mechanisms other than those targeted by AChEIs underlie the pathogenesis of AD. Dysfunctional glutamatergic neurotransmission, particularly that mediated by the N-methyl-D-aspartate (NMDA) receptor, has been reported to play a role in the pathophysiology of AD. The NMDA receptor (NMDAR) regulates synaptic plasticity, memory, and cognition, and the attenuation of NMDAR-mediated neurotransmission can result in impaired neuroplasticity and cognitive deficits in the aging brain. Furthermore, NMDARs also interact with amyloid beta peptide/amyloid precursor protein and tau protein, whose production represents the main manifestations of AD. In this paper, we review the evidence supporting NMDA dysfunction in both animal models of AD and patients afflicted with AD, and we also review the literature that suggests that NMDA-enhancing agents such as glycine and D-cycloserine can improve cognitive functions. The benefits and limitations of NMDAR antagonists that can diminish the excitatory neurotoxicity triggered by glutamate are also addressed in relation to AD. We propose that enhancing glutamatergic neurotransmission by activating the NMDAR may be effective in treating the cognitive decline that occurs in AD. Prospective studies on AD in which NMDA-enhancing agents are used are required to verify this hypothesis and confirm the long-term efficacy and safety of the treatment agents.
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Enfermedad de Alzheimer/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , N-Metilaspartato/metabolismo , Anciano , Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Animales , Encéfalo/metabolismo , Encéfalo/fisiopatología , Disfunción Cognitiva/fisiopatología , Modelos Animales de Enfermedad , Diseño de Fármacos , Humanos , Plasticidad Neuronal/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Transmisión Sináptica/fisiologíaRESUMEN
BACKGROUND: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. METHODS: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women) were recruited. Four single nucleotide polymorphisms (SNP) of MET (rs2237717, rs41735, rs42336, and rs1858830) and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Thorough neurocognitive functions were also assessed. RESULTS: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration), and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5%) performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM). In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM), even when neurocognitive functions were controlled (p = 0.046 by GLM). CONCLUSIONS: To our knowledge, this is the first study to suggest that genetic factors can affect performance of facial emotion perception. The findings indicate that MET variances and MET/AKT interaction may affect facial emotion perception, implicating that the MET/AKT cascade plays a significant role in facial emotion perception. Further replication studies are needed.