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1.
Biomed Pharmacother ; 175: 116649, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692059

RESUMEN

BACKGROUND: Second-generation antipsychotics increase the risk of atrial fibrillation. This study explores whether the atypical antipsychotic ziprasidone triggers inflammasome signaling, leading to atrial arrhythmia. METHODS: Electromechanical and pharmacological assessments were conducted on the rabbit left atria (LA). The patch-clamp technique was used to measure ionic channel currents in single cardiomyocytes. Detection of cytosolic reactive oxygen species production was performed in atrial cardiomyocytes. RESULTS: The duration of action potentials at 50 % and 90 % repolarization was dose-dependently shortened in ziprasidone-treated LA. Diastolic tension in LA increased after ziprasidone treatment. Ziprasidone-treated LA showed rapid atrial pacing (RAP) triggered activity. PI3K inhibitor, Akt inhibitor and mTOR inhibitor abolished the triggered activity elicited by ziprasidone in LA. The NLRP3 inhibitor MCC950 suppressed the ziprasidone-induced post-RAP-triggered activity. MCC950 treatment reduced the reverse-mode Na+/Ca2+ exchanger current in ziprasidone-treated myocytes. Cytosolic reactive oxygen species production decreased in ziprasidone-treated atrial myocytes after MCC950 treatment. Protein levels of inflammasomes and proinflammatory cytokines, including NLRP3, caspase-1, IL-1ß, IL-18, and IL-6 were observed to be upregulated in myocytes treated with ziprasidone. CONCLUSIONS: Our findings suggest ziprasidone induces atrial arrhythmia, potentially through upregulation of the NLRP3 inflammasome and enhancement of reactive oxygen species production via the PI3K/Akt/mTOR pathway.


Asunto(s)
Fibrilación Atrial , Inflamasomas , Miocitos Cardíacos , Piperazinas , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Conejos , Especies Reactivas de Oxígeno/metabolismo , Piperazinas/farmacología , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Tiazoles/farmacología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Potenciales de Acción/efectos de los fármacos , Antipsicóticos/farmacología
2.
J Psychiatr Res ; 172: 108-118, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38373372

RESUMEN

In the neurodevelopmental model of schizophrenia, minor physical anomalies (MPAs) are considered neurodevelopmental markers of schizophrenia. To date, there has been no research to evaluate the interaction between MPAs. Our study built and used a machine learning model to predict the risk of schizophrenia based on measurements of MPA items and to investigate the potential primary and interaction effects of MPAs. The study included 470 patients with schizophrenia and 354 healthy controls. The models used are classical statistical model, Logistic Regression (LR), and machine leaning models, Decision Tree (DT) and Random Forest (RF). We also plotted two-dimensional scatter diagrams and three-dimensional linear/quadratic discriminant analysis (LDA/QDA) graphs for comparison with the DT dendritic structure. We found that RF had the highest predictive power for schizophrenia (Full-training AUC = 0.97 and 5-fold cross-validation AUC = 0.75). We identified several primary MPAs, such as the mouth region, high palate, furrowed tongue, skull height and mouth width. Quantitative MPA analysis indicated that the higher skull height and the narrower mouth width, the higher the risk of schizophrenia. In the interaction, we further identified that skull height and mouth width, furrowed tongue and skull height, high palate and skull height, and high palate and furrowed tongue, showed significant two-item interactions with schizophrenia. A weak three-item interaction was found between high palate, skull height, and mouth width. In conclusion, we found that the two machine learning methods showed good predictive ability in assessing the risk of schizophrenia using the primary and interaction effects of MPAs.


Asunto(s)
Esquizofrenia , Lengua Fisurada , Humanos , Modelos Logísticos , Aprendizaje Automático , Modelos Estadísticos
3.
Biomedicines ; 10(5)2022 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-35625713

RESUMEN

BACKGROUND: Atypical antipsychotics increase the risk of atrial arrhythmias and sudden cardiac death. This study investigated whether ziprasidone, a second-generation antipsychotic, affected intracellular Ca2+ and Na+ regulation and oxidative stress, providing proarrhythmogenic substrates in atriums. METHODS: Electromechanical analyses of rabbit atrial tissues were conducted. Intracellular Ca2+ monitoring using Fluo-3, the patch-clamp method for ionic current recordings, and a fluorescence study for the detection of reactive oxygen species and intracellular Na+ levels were conducted in enzymatically dissociated atrial myocytes. RESULTS: Ziprasidone-treated atriums showed sustained triggered activities after rapid pacing, which were inhibited by KN-93 and ranolazine. A reduced peak L-type Ca2+ channel current and enhanced late Na+ current were observed in ziprasidone-treated atrial myocytes, together with an increased cytosolic Na+ level. KN-93 suppressed the enhanced late Na+ current in ziprasidone-treated atrial myocytes. Atrial myocytes treated with ziprasidone showed reduced Ca2+ transient amplitudes and sarcoplasmic reticulum (SR) Ca2+ stores, and increased SR Ca2+ leakage. Cytosolic and mitochondrial reactive oxygen species production was increased in atrial myocytes treated with ziprasidone. TNF-α and NLRP3 were upregulated in ziprasidone-treated myocytes, and the level of phosphorylated calcium/calmodulin-dependent protein kinase II protein was increased. CONCLUSIONS: Our results suggest that ziprasidone increases the occurrence of atrial triggered activity and causes intracellular Ca2+ and Na+ dysregulation, which may result from enhanced oxidative stress and activation of the TNF-α/NLRP3 inflammasome pathway in ziprasidone-treated myocytes.

4.
Schizophrenia (Heidelb) ; 8(1): 4, 2022 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-35210439

RESUMEN

In support of the neurodevelopmental model of schizophrenia, minor physical anomalies (MPAs) have been suggested as biomarkers and potential pathophysiological significance for schizophrenia. However, an integrated, clinically useful tool that used qualitative and quantitative MPAs to visualize and predict schizophrenia risk while characterizing the degree of importance of MPA items was lacking. We recruited a training set and a validation set, including 463 schizophrenia patients and 281 healthy controls to conduct logistic regression and the least absolute shrinkage and selection operator (Lasso) regression to select the best parameters of MPAs and constructed nomograms. Two nomograms were built to show the weights of these predictors. In the logistic regression model, 11 out of a total of 68 parameters were identified as the best MPA items for distinguishing between patients with schizophrenia and controls, including hair whorls, epicanthus, adherent ear lobes, high palate, furrowed tongue, hyperconvex fingernails, a large gap between first and second toes, skull height, nasal width, mouth width, and palate width. The Lasso regression model included the same variables of the logistic regression model, except for nasal width, and further included two items (interpupillary distance and soft ears) to assess the risk of schizophrenia. The results of the validation dataset verified the efficacy of the nomograms with the area under the curve 0.84 and 0.85 in the logistic regression model and lasso regression model, respectively. This study provides an easy-to-use tool based on validated risk models of schizophrenia and reflects a divergence in development between schizophrenia patients and healthy controls ( https://www.szprediction.net/ ).

5.
NPJ Schizophr ; 7(1): 35, 2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-34226568

RESUMEN

Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) are neurological abnormalities that may be intermediate phenotypes or endophenotypes for schizophrenia. Our previous study found poorer performance on NSS tests from patients with EOS and their unaffected first-degree relatives. Thus, we aimed to identify a set of aberrant neurodevelopmental-related miRNAs that could serve as potential biomarkers for EOS or schizophrenia with NSS. This study included 215 schizophrenia patients (104 EOS and 111 AOS), 72 unaffected first-degree relatives, 31 patients with bipolar disorder, and 100 healthy controls. Differential expression analysis revealed that miR-137, miR-34b, and miR-34c were significantly up-regulated in patients with schizophrenia and their unaffected first-degree relatives compared to healthy controls. Receiver operating characteristic (ROC) analysis showed that the miR-137 expression signature could be used to discriminate between patients with EOS and healthy controls (AUC = 0.911). Additionally, miR-34b had the highest ability to discriminate between EOS and AOS (AUC = 0.810), which may indicate different aetiological pathways to disease onset. Moreover, miR-137 dysregulation was correlated with almost all NSS subscales (i.e., sensory integration, motor sequencing, etc.) and, when EOS patients with NSS, miR-137 expression discriminated these patients from healthy controls to a greater extent (AUC = 0.957). These findings support the potential for neurodevelopmental-related miRNAs to be used as indicators of vulnerability to EOS.

6.
Int J Med Sci ; 17(2): 255-262, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32038109

RESUMEN

Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1ß, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.


Asunto(s)
Biomarcadores/sangre , Citocinas/sangre , Esquizofrenia/sangre , Adulto , Edad de Inicio , Femenino , Humanos , Interleucina-10/sangre , Interleucina-4/sangre , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad
7.
J Clin Med ; 8(9)2019 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-31514416

RESUMEN

Age at onset is one of the most important clinical features of schizophrenia that could indicate greater genetic loadings. Neurological soft signs (NSS) are considered as a potential endophenotype for schizophrenia. However, the association between NSS and different age-onset schizophrenia still remains unclear. We aimed to compare risk model in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with NSS. This study included 262 schizophrenia patients, 177 unaffected first-degree relatives and 243 healthy controls. We estimated the discriminant abilities of NSS models for early-onset schizophrenia (onset age < 20) and adult-onset schizophrenia (onset age ≥ 20) using three data mining methods: artificial neural networks (ANN), decision trees (DT) and logistic regression (LR). We then assessed the magnitude of NSS performance in EOS and AOS families. For the four NSS subscales, the NSS performance were greater in EOS and AOS families compared with healthy individuals. More interestingly, there were significant differences found between patients' families and control group in the four subscales of NSS. These findings support the potential for neurodevelopmental markers to be used as schizophrenia vulnerability indicators. The NSS models had higher discriminant abilities for EOS than for AOS. NSS were more accurate in distinguishing EOS patients from healthy controls compared to AOS patients. Our results support the neurodevelopmental hypothesis that EOS has poorer performance of NSS than AOS. Hence, poorer NSS performance may be imply trait-related NSS feature in EOS.

8.
Sleep Breath ; 21(2): 243-253, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27495797

RESUMEN

PURPOSE: The symptoms of sleep apnea, such as sleep fragmentation and oxygen desaturation, might be risk factors for subsequent mood disorder (MD), but associations between sleep apnea and MD remain unclear. This nationwide population-based study thus aimed to identify the risk of MD in patients with vs. without sleep apnea. METHODS: This cohort study used data from the National Health Insurance database. In total, 5415 patients diagnosed with sleep apnea between 2000 and 2010 were evaluated, and 27,075 matched non-sleep apnea enrollees were included as a comparison cohort. All subjects were followed until 2011. The Cox proportional hazard ratio (HR) was used to investigate the relationship between MD and sleep apnea while controlling covariates and comorbidities of sleep apnea. RESULTS: Of 5415, 154 patients with sleep apnea (2.84 %) were diagnosed with MD during the follow-up period in comparison with 306 of 27,075 individuals (1.13 %) without antecedent sleep apnea. After adjusting for the selected factors and comorbidities, we found that patients with sleep apnea were from 1.82- to 2.07-fold greater risk of MD than the comparisons. Of the three subcategories of MD (major depressive disorder, bipolar disorder, and unspecified MD), sleep apnea had the highest predisposing risk with respect to major depressive disorder (adjusted HR from 1.82 to 2.07) and bipolar disorder (adjusted HR from 2.15 to 3.24). CONCLUSIONS: There is a greater likelihood of MD manifesting in patients with a history of sleep apnea. Health professionals are thus advised to carefully monitor the psychological impacts of sleep apnea.


Asunto(s)
Trastornos del Humor/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Adulto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/epidemiología , Causalidad , Estudios de Cohortes , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Modelos de Riesgos Proporcionales , Riesgo , Apnea Obstructiva del Sueño/diagnóstico , Taiwán
9.
Medicine (Baltimore) ; 95(30): e4406, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27472737

RESUMEN

Age at onset is the most important feature of schizophrenia that could indicate its origin. Minor physical anomalies (MPAs) characterize potential marker indices of disturbances in early neurodevelopment. However, the association between MPAs and age at onset of schizophrenia is still unclear. We aimed to compare risk assessment and familial aggregation in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with MPAs and craniofacial measures.We estimated the risk assessment of MPAs among patients with EOS (n = 68), patients with AOS (n = 183), nonpsychotic relatives (n = 147), and healthy controls (n = 241) using 3 data-mining algorithms. In addition, we assessed the magnitude of familial aggregation of MPAs with respect to the age at onset of schizophrenia.The performance of EOS was superior to that of AOS, with discrimination accuracies of 89% and 76%, respectively. Combined MPA scores as the risk assessment were significantly higher in all schizophrenia subgroups and the nonpsychotic relatives of EOS patients than in the healthy controls. The recurrence risk ratio for familial aggregation of the MPA scores of EOS families (odds ratio 9.27) was substantially higher than that of AOS families (odds ratio 2.47).The results highlight that EOS improves risk assessment and has a severe magnitude of familial aggregation of MPAs. These findings indicate that EOS might result from a stronger genetic susceptibility to neurodevelopmental deficits.


Asunto(s)
Cefalometría , Anomalías Congénitas/genética , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Medición de Riesgo , Esquizofrenia/genética , Adolescente , Adulto , Edad de Inicio , Femenino , Pruebas Genéticas , Humanos , Masculino , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/genética , Esquizofrenia/diagnóstico , Taiwán , Adulto Joven
10.
J Affect Disord ; 157: 80-6, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24581832

RESUMEN

BACKGROUND: Associations of two voltage-gated calcium channel (Cav) genes, CACNA1C and CACNB2, were identified for bipolar disorder (BP) in different ethnic groups in recent genome-wide association studies. The current study aimed to evaluate the associations of several Cav genes and subtypes of BP in genetically more homogeneous Taiwanese samples. Additionally, we tested interaction effects among genes that encode for α1, ß and γ-subunits of calcium channel. METHODS: 8 Cav genes were selected based on evidence in prior association studies and significant linkage regions for BP. 280 BP patients and 200 controls were recruited. Multifactor dimensionality reduction was performed for interaction testing in these discovery samples. Replication was conducted for two markers using additional 495 Taiwanese cases and 1341 controls. RESULTS: Weak associations for CACNA1C (rs10848635), CACNA1E (rs10848635), CACNB2 (rs11013860), and CACNG2 (rs2284018) genes were observed. Joint analysis of four markers revealed higher accumulative risk with increasing numbers of risk genotypes an individual endorsed for BP-I (Ptrend=0.006) and BP-II (Ptrend=0.017) disorders. Combined analysis with independent replication samples further supported the association of rs11013860 in CACNB2 with BP subtype I (P=1×10(-6)). Suggestive interactions were found between genes encoded for different subunits of calcium channel (α1, ß, and γ). LIMITATIONS: Moderate sample size and incomplete markers coverage for the chosen Cav genes. CONCLUSIONS: Our results support the involvement of different calcium channel genes in bipolar illness, in particular the beta-subunit in the Asian population. Further investigation of functional property of these genes can contribute on understanding the etiological mechanisms of bipolar illness.


Asunto(s)
Trastorno Bipolar/genética , Canales de Calcio/genética , Pueblo Asiatico/genética , Femenino , Ligamiento Genético , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Taiwán
11.
J Psychosom Res ; 76(1): 61-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24360143

RESUMEN

OBJECTIVE: Sleep disturbances are frequently observed in major depressive (MDD) and bipolar disorder (BD). This study reported sleep profiles of patients and their relatives versus controls, and examined the familiality of sleep features in mood disorder families. We also evaluated the influences of sleep disturbance on patients' quality of life (QOL), functional impairment, and suicidality. METHODS: We recruited 363 BD and 157 MDD patients, 521 first-degree relatives, and 235 healthy controls, which completed a diagnostic interview, Pittsburgh Sleep Quality Index (PSQI), and QOL questionnaire. The magnitude of heritability of sleep features was calculated and familiality was evaluated by mixed regression models and intraclass correlation coefficient (ICC). The associations between sleep problems and clinical outcomes were examined using multiple regression models. RESULTS: More than three-quarters of mildly-ill patients were classified as "poor sleepers". MDD patients had significantly worse sleep quality as compared to BD patients. Moderate but significant familial aggregation was observed in subjective sleep quality, sleep latency, disturbance, daytime dysfunction, and global score (ICC=0.10-0.21, P<.05). Significant heritability was found in sleep quality (0.45, P<.001) and sleep disturbance (0.23, P<.001). Patients with good sleep quality had better QOL and less functional impairment (P<.05) than poor sleepers. Poor sleep quality and nightmares further increased the risk for suicidal ideation (ORadj=2.8) and suicide attempts (ORadj=1.9-2.8). CONCLUSION: Subjectively measured sleep features demonstrated significant familiality. Poor sleep quality further impaired patients' daily function and QOL, in addition to increasing the risk of suicidality, and thus requires special attention in related clinical settings.


Asunto(s)
Trastorno Bipolar/complicaciones , Trastorno Depresivo Mayor/complicaciones , Calidad de Vida , Trastornos del Sueño-Vigilia/psicología , Ideación Suicida , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Riesgo , Sueño , Intento de Suicidio/psicología , Encuestas y Cuestionarios
12.
J Affect Disord ; 138(3): 367-74, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22331025

RESUMEN

OBJECTIVE: Personality traits have impacts on individuals' response to stress and mood expression. The current study aimed to investigate the profile of personality traits in patients with bipolar disorders and major depressive disorder (MDD). Familial aggregation of personality traits in mood disorder families was also evaluated. METHODS: We recruited 260 clinical patients of MDD (92), bipolar disorder-I and II (BP-I=111, BP-II=57), 190 first-degree relatives, and 180 controls. Four personality traits were assessed using the Eysenck and Tridimensional Personality Questionnaires, including Extraversion (E), Neuroticism (N), Harm Avoidance (HA), and Novelty Seeking (NS). The magnitude of familiality of personality traits in mood disorder families was evaluated by mixed models and intra-class correlation coefficients (ICC). RESULTS: Patients with mood disorders had lower E, and higher N, HA and NS than controls. Unaffected relatives were not differed from controls in the four personality traits. BP-I had higher E, NS and lower N, HA than MDD patients (p<0.01). The scale N further distinguished BP-I from BP-II (p=0.02) with lower N among BP-I patients. There exhibited moderate familiality in E (ICC=0.184-0.239) and HA (ICC=0.355) in bipolar disorder families. LIMITATION: Personality traits were accessed cross-sectionally without quantitatively controlled severity of mood symptoms. CONCLUSION: Different patterns of personality traits distinguish patients from unaffected individuals as well as separate diagnoses of mood disorders, indicating the usage of more comprehensive evaluation of personality traits in clinical settings. Familiality of extraversion and harm avoidance in bipolar disorder families provides insights for further investigating correlates of comorbid behavioral problems in bipolar disorders.


Asunto(s)
Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Personalidad , Adulto , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inventario de Personalidad
13.
J Affect Disord ; 136(1-2): 81-89, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21906818

RESUMEN

OBJECTIVE: Bipolar-I disorder (BPI) often co-occurred with anxiety (ANX) and substance use disorders (SUD), which poses challenges in public health and clinical treatment, and adds complexity in searching for relevant etiologic factors. The present study sought to identify subgroups of BPI patients using comorbidity patterns with ANX and SUD. METHODS: Clinical patients (N=306) diagnosed with BPI were recruited and interviewed using the Composite International Diagnostic Interview to collect data on demographics and clinical features, including episodic information, impairments, and lifetime diagnoses of ANX (panic, agoraphobia, generalized anxiety disorder, specific and social phobia) and SUD (nicotine dependence, alcohol use and drug use disorder). We applied latent class analysis to empirically derive classes of BPI. A number of exogenous variables were examined for each class. RESULTS: A three-class model provides excellent discriminability for subgrouping BPI patients with different comorbidity patterns. The BPI-LOW class (83.99%) had more pure mania without most lifetime comorbidity, higher numbers of last year mania episodes, and less suicidality and impairments. The BPI-ANX class (3.60%) was female predominant, tended to comorbid with multiple anxiety disorders but no SUD, and had early onset age. The BPI-SUD class (12.42%) was male predominant, had high prevalence of lifetime SUD and frequent mood episodes in the last year. Both the BPI-ANX and BPI-SUD classes had severe functional impairments and suicidal behaviors. LIMITATIONS: Clinical information was retrospectively collected. Besides, we did not comprehensively access lifetime comorbidity for all psychiatric disorders. CONCLUSION: The three empirically identified subgroups of BPI patients exhibited distinguished comorbidity patterns and clinical features, including suicidal behaviors, frequent mood episodes and functional impairments. Our findings have clinical implication in intervention and treatment as well as to explore their different underlying mechanisms.


Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Bipolar/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán/epidemiología , Adulto Joven
14.
Biol Pharm Bull ; 33(10): 1685-91, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20930376

RESUMEN

α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Movimiento Celular/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Melanoma/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Extractos Vegetales/farmacología , Solanina/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , FN-kappa B/metabolismo , Invasividad Neoplásica/prevención & control , Fosforilación , Fitoterapia , Extractos Vegetales/uso terapéutico , Brotes de la Planta , Transducción de Señal/efectos de los fármacos , Solanina/uso terapéutico , Solanum tuberosum/química
15.
Biol Pharm Bull ; 33(4): 622-30, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20410596

RESUMEN

alpha-Chaconine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation, migration, invasion, and inducing apoptosis of tumor cells. However, the effect of alpha-chaconine on tumor angiogenesis remains unclear. In the present study, we examined the effect of alpha-chaconine on angiogenesis in vitro. Data demonstrated that alpha-chaconine inhibited proliferation of bovine aortic endothelial cells (BAECs) in a dose-dependent manner. When treated with non-toxic doses of alpha-chaconine, cell migration, invasion and tube formation were markedly suppressed. Furthermore, alpha-chaconine reduced the expression and activity of matrix metalloproteinase-2 (MMP-2), which is involved in angiogenesis. Our biochemical assays indicated that alpha-chaconine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK) and p38. In addition, alpha-chaconine significantly increased the cytoplasmic level of inhibitors of kappaBalpha (IkappaBalpha) and decreased the nuclear level of nuclear factor kappa B (NF-kappaB), suggesting that alpha-chaconine could inhibit NF-kappaB activity. Furthermore, the treatment of inhibitors specific for JNK (SP600125), PI3K (LY294002) or NF-kappaB (pyrrolidine dithiocarbamate) to BAECs reduced tube formation. Taken together, the results suggested that alpha-chaconine inhibited migration, invasion and tube formation of BAECs by reducing MMP-2 activities, as well as JNK and PI3K/Akt signaling pathways and inhibition of NF-kappaB activity. These findings reveal a new therapeutic potential for alpha-chaconine on anti-angiogenic therapy.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Extractos Vegetales/farmacología , Solanina/análogos & derivados , Solanum tuberosum/química , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Bovinos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Plantones , Solanina/farmacología , Solanina/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
16.
Burns ; 33(5): 649-52, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17482369

RESUMEN

This cross-sectional study was conducted to examine the prevalence and risk factors of post-traumatic stress disorder (PTSD) after severe burn, and the need for psychological intervention for burn patients in southern Taiwan. Participants (N=82) were assessed by means of the Mini-International Neuropsychiatry Interview (MINI) scale with a structured questionnaire. Results showed that the prevalence of post-traumatic stress disorder in burn patients who met the DSM-IV criteria for PTSD was 26.8%. The risk factors related to PTSD in burn patients were: female, unmarried, and a lack of leisure arrangements after adjusting for confounding factors. PTSD patients needed more psychological intervention than the non-PTSD patients. These results suggest that PTSD after severe burn was not uncommon in southern Taiwan. The identified risk factors could provide clues to help burn care professionals provide multidisciplinary intervention.


Asunto(s)
Quemaduras/psicología , Trastornos por Estrés Postraumático/etiología , Adolescente , Adulto , Anciano , Quemaduras/epidemiología , Estudios Transversales , Femenino , Humanos , Actividades Recreativas , Masculino , Estado Civil , Persona de Mediana Edad , Prevalencia , Psicoterapia/métodos , Factores de Riesgo , Factores Sexuales , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/terapia , Taiwán/epidemiología
17.
J Psychiatr Res ; 41(1-2): 90-6, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-16325854

RESUMEN

OBJECTIVE: To prospectively evaluate the relationship between the clinical course of posttraumatic stress symptoms (PTSS) and quality of life (QOL) among Taiwan earthquake survivors for 3 years. METHODS: A population survey was done in a Taiwan township near the epicenter of a severe earthquake (7.3 on the Richter scale). Trained assistants used the Medical Outcomes Study Short Form-36 (MOS SF-36) and the Disaster-Related Psychological Screening Test to interview earthquake survivors 16 and older. A total of 1756 respondents were surveyed during the 3-year follow-up period. RESULTS: At 0.5 and 3 years after the earthquake, the estimated rate of PTSS (cutoff point, 3/4) was 23.8% and 4.4%, respectively. The survivors with PTSS scored lower for each concept of the MOS SF-36 at these two intervals. Three years after the earthquake, the survivors in the persistently healthy group showed the highest scores in all subscales and domains of the MOS SF-36; second-highest was the recovering group; third-highest was the delayed PTSS group; and the persistent PTSS group showed the lowest scores in all concepts and domains. Notably, survivors with delayed onset PTSS exhibited a lower QOL when PTSS occurred. CONCLUSIONS: Three years after the earthquake, the estimated rate of PTSS had declined, and the QOL of the survivors varied according to how their PTSS had progressed.


Asunto(s)
Desastres/estadística & datos numéricos , Calidad de Vida/psicología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Sobrevivientes/psicología , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Áreas de Influencia de Salud , Femenino , Estudios de Seguimiento , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/diagnóstico , Encuestas y Cuestionarios , Taiwán/epidemiología
18.
J Formos Med Assoc ; 104(5): 308-17, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15959597

RESUMEN

BACKGROUND AND PURPOSE: The catastrophic Chi-Chi earthquake of September 21, 1999 in Taiwan provided a unique opportunity to study the disaster's psychiatric impact on survivors. This study assessed the development of psychiatric disorders among residents in a Taiwanese village near the epicenter of the earthquake within 6 months of the disaster. METHODS: A total of 442 of the 602 actual living residents of Tong-Chi village who were over 16 years of age and were present in the community at the time of the earthquake were included in this population survey. Subjects were interviewed by psychiatrists using the Mini-International Neuropsychiatric Interview and questionnaires to collect demographic information and risk factors for psychiatric disorders 4 to 6 months after the earthquake. RESULTS: The prevalence rates were 9.5% for current major depression, 2.8% for past major depressive episode, and 7.9% for post-traumatic stress disorder (PTSD). Females had significantly higher rates of most psychiatric disorders. After controlling for covariates, the significant risk factors for PTSD were female gender and having sought medical service after the earthquake. Significant risk factors for major depressive episode were divorced/widowed status, education level equal to or below primary school, and prominent house damage. CONCLUSION: This population survey of earthquake disaster survivors found an increased prevalence of psychiatric disorders after exposure to a catastrophic earthquake. These results highlight the need for prompt therapeutic attention to residents of earthquake disaster areas after the event.


Asunto(s)
Trastorno Depresivo/epidemiología , Desastres , Trastornos por Estrés Postraumático/epidemiología , Sobrevivientes/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Taiwán/epidemiología
19.
Aust N Z J Psychiatry ; 38(5): 358-64, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15144515

RESUMEN

OBJECTIVE: To investigate quality of life and related risk factors of Taiwanese earthquake survivors with different psychiatric disorders 21 months after the earthquake. METHOD: This was a population survey. Trained assistants used the Medical Outcomes Study Short Form-36 (MOS SF-36) and questionnaires to interview 461 respondents (209 males and 252 females) 16 years or older who were equally exposed to the earthquake. Psychiatrists interviewed the same respondents using the Mini-International Neuropsychiatric Interview (MINI), with an adjusted response rate of 79.9%. RESULTS: The prevalence of varied psychiatric disorders in earthquake survivors ranged from 3.3% to 18%. However, there was almost a positive trend in quality of life in survivors among the following groups: posttraumatic stress disorder combined with major depressive episode; major depressive episode; posttraumatic stress disorder; other psychiatric diseases; and healthy mentality groups on the physical aspect or mental aspect of the MOS SF-36. When survivors were elderly or female and had experienced prominent financial loss immediately after the earthquake, social network change, and mental impairment, their quality of life tended to be worse. CONCLUSION: The earthquake survivors had a higher percentage of psychiatric disorders. The risk factors that affected quality of life in survivors were age, female sex, financial loss, social network change, and mental impairment.


Asunto(s)
Desastres , Calidad de Vida , Población Rural/estadística & datos numéricos , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/etnología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Psicología , Factores de Riesgo , Factores Socioeconómicos , Trastornos por Estrés Postraumático/epidemiología , Taiwán/epidemiología , Factores de Tiempo
20.
Aust N Z J Psychiatry ; 37(1): 97-103, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12534664

RESUMEN

OBJECTIVE: To create a short screening scale for the detection of posttraumatic stress disorder (PTSD) and major depressive disorder (MDE) in earthquake survivors in Taiwan. METHOD: Trained research assistants used the Disaster-Related Psychological Screening Test (DRPST) to assess 461 residents of a village that had experienced a major earthquake. The participants were also evaluated by psychiatrists using the Mini-International Neuro-psychiatric Interview (MINI). Best subset regression analysis and the receiver operating characteristics curve were used to select a subset of items and cut-off points from the DRPST. RESULTS: A seven-symptom scale and a three-symptom analogue were selected for PTSD and MDE screening, respectively. Scores of three or more on the PTSD scale and two or more on the MDE scale were used to define a group of positive cases that provide useful information for the patient cohort and will be valuable in long-term follow-up studies of the prevalence of psychiatric diseases following a natural disaster. However, higher scores could also be used to define positive cases under limited psychiatric care resources. CONCLUSION: The DRPST, which was administered for phase 1 of this two-phase study, may be used for effective and rapid screening for PTSD and MDE after an earthquake, despite the usual limitations on resources following a disaster.


Asunto(s)
Desastres , Tamizaje Masivo , Pruebas Psicológicas , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Áreas de Influencia de Salud , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/psicología , Sobrevivientes/psicología , Sobrevivientes/estadística & datos numéricos , Taiwán/epidemiología
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