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2.
Neuroimage ; : 116831, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32438048

RESUMO

Brain age prediction models using diffusion magnetic resonance imaging (dMRI) and machine learning techniques enable individual assessment of brain aging status in healthy people and patients with brain disorders. However, dMRI data are notorious for high intersite variability, prohibiting direct application of a model to the datasets obtained from other sites. In this study, we generalized the dMRI-based brain age model to different dMRI datasets acquired under different imaging conditions. Specifically, we adopted a transfer learning approach to achieve domain adaptation. To evaluate the performance of transferred models, a brain age prediction model was constructed using a large dMRI dataset as the source domain, and the model was transferred to three target domains with distinct acquisition scenarios. The experiments were performed to investigate (1) the tuning data size needed to achieve satisfactory performance for brain age prediction, (2) the feature types suitable for different dMRI acquisition scenarios, and (3) performance of the transfer learning approach compared with the statistical covariate approach. By tuning the models with relatively small data size and certain feature types, optimal transferred models were obtained with significantly improved prediction performance in all three target cohorts (p < 0.001). The mean absolute error of the predicted age was reduced from 13.89 to 4.78 years in Cohort 1, 8.34 to 5.35 years in Cohort 2, and 8.74 to 5.64 years in Cohort 3. The test-retest reliability of the transferred model was verified using dMRI data acquired at two timepoints (intraclass correlation coefficient = 0.950). Clinical sensitivity of the brain age prediction model was investigated by estimating the brain age in patients with schizophrenia. The prediction made by the transferred model was not significantly different from that made by the reference model. Both models predicted significant brain aging in patients with schizophrenia as compared with healthy controls (p < 0.001); the predicted age difference of the transferred model was 4.63 and 0.26 years for patients and controls, respectively, and that of the reference model was 4.39 and -0.09 years, respectively. In conclusion, transfer learning approach is an efficient way to generalize the dMRI-based brain age prediction model. Appropriate transfer learning approach and suitable tuning data size should be chosen according to different dMRI acquisition scenarios.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32227530

RESUMO

INTRODUCTION: Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS: Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval < 20 ms), CV < 0.3 m/s and local fractionated electrograms were evaluated. RESULTS: Twenty-six complex ATs were mapped (mean: 1.3 ± 0.7 maps/pt; 4 focal, 22 isthmus-dependent). Coherent mapping was better in identifying CI/breakout sites where ablation terminated the tachycardia (96.2% vs 69.2%; P = .010) and identified significantly more CI (mean/chamber 2.0 ± 1.1 vs 1.0 ± 0.7; P < .001) with narrower width (19.8 ± 10.5 vs 43.0 ± 23.9 mm; P < .001) than conventional mapping. Ablation at origin and CI sites was successful in 25 (96.2%) with long-term recurrence in 25%. CONCLUSIONS: Coherent mapping with conduction velocity vectors derived from adjacent mapping sites significantly improved the identification of CI sites in scar-related ATs with isthmus-dependent re-entry better than conventional mapping. It may be used in conjunction with conventional mapping strategies to facilitate recognition of slow conduction areas and critical sites that are important targets of ablation.

4.
Eur J Clin Invest ; : e13247, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32307703

RESUMO

BACKGROUND: The mechanism underlying the occurrence of the J wave in low temperature remains unclear. However, low temperature is associated with metabolic disorder and 5' AMP-activated protein kinase (AMPK), which modulates ionic currents and cardiac metabolism. This study investigated whether AMPK regulation can modulate the occurrence of the J wave at low temperature. METHODS: Unipolar and bipolar leads were used to record monophasic action potential (the endocardium and epicardium) and pseudo-electrocardiograms (inferior leads) to study the cardiac electrical activity. Measurements were taken in isolated Langendorff rabbit hearts at both 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, IKur , 50 µmol L-1 ), PF06409577 (an AMPK activator, 1 µmol L-1 ), compound C (an AMPK inhibitor, 10 µmol L-1 ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, IKATP , 20 µmol L-1 ). RESULTS: The amplitude of the J wave (2.46 ± 0.34 mV vs. 1.11 ± 0.23 mV, P < .01) at 30℃ (n = 15) was larger than that at 37℃ (n = 15). PF06409577 (1 µmol L-1 ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10 µmol L-1 ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50 µmol L-1 ) and glibenclamide (20 µmol L-1 ). CONCLUSIONS: AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating IKATP and IKur channels.

5.
Heart Rhythm ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32028045

RESUMO

BACKGROUND: Whether ectopic atrial rhythm (EAR) is a high-risk cardiovascular phenotype (eg, the manifestation of a diseased sinoatrial node) or just a benign accelerated ectopic pacemaker remains unclear. OBJECTIVE: We aimed to analyze the cardiovascular outcomes and underlying mechanisms in patients with EAR. METHODS: From a 12-lead electrocardiogram hospital-based electrocardiogram database, a total of 2896 adults with EAR were propensity score matched at 1:5 with 14,480 patients with sinus rhythm (SR). Patients were retrospectively followed up for cardiovascular mortality (the primary outcome) and permanent pacemaker implantation (the secondary outcome). Heart rate variability was analyzed to compare autonomic function between patients with EAR and those with SR. RESULTS: The prevalence of EAR was 1.13%, which increased with age. Compared with the matched patients, those with EAR had a higher risk of cardiovascular mortality (adjusted hazard ratio 1.93; 95% confidence interval 1.52-2.44; P < .0001) and permanent pacemaker implantation (adjusted hazard ratio 5.94; 95% confidence interval 3.89-9.09; P < .0001) according to the Cox proportional hazards regression model. The risk of cardiovascular mortality was similar across the subgroups on the basis of age, sex, hypertension, type 2 diabetes mellitus, congestive heart failure, myocardial infarction, stroke, and chronic kidney diseases. In patients with EAR, the low frequency/high frequency and standard deviation of the mean normal-to-normal intervals/root mean square of successive differences ratios for heart rate variability were both lower than those in patients with SR. This implied autonomic imbalance in patients with EAR. CONCLUSION: Patients with EAR have a higher risk of cardiovascular mortality and permanent pacemaker implantation, which was associated with autonomic imbalance.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31954755

RESUMO

Several studies have suggested a higher oxidative stress in schizophrenia. However, the implications of oxidative stress on clinical symptoms remain unclear. This study aimed to investigate the platelet oxidative stress in different stages of schizophrenia (i.e., chronic stable and acute relapse) in order to clarify the clinical implications of oxidative stress and the treatment effects. We recruited 43 chronic stable patients with schizophrenia and 48 non-psychiatric controls. Platelets were collected for measuring the levels of nitric oxide (NO), lipid peroxidation (LPO), and glutathione (GSH) and the activity of GSH peroxidase (GPx) and superoxide dismutase (SOD). The levels and activity were compared between patients and controls and were examined for their relationship with clinical severity. Further, we evaluated the changes of levels and activity before and after treatment in an independent sample with acute relapse (N = 19). Patients with chronic stable schizophrenia had lower SOD activity compared to non-psychiatric controls. In chronic stable patients, NO level was positively correlated with positive and disorganized symptoms, while the GPx activity were negatively correlated with excitement. In patients with acute relapse, the levels and activity were not different before and after four weeks of antipsychotic treatment, but LPO level was negatively correlated with pretreatment disorganized symptoms. The change of LPO can also predict the change of disorganized symptoms and negative symptoms. Our findings suggest that platelet SOD was lower in chronic stable schizophrenia. Platelet LPO may be associated with less disorganized symptoms in acute relapse patients and better treatment response.

7.
Asia Pac Psychiatry ; 12(1): e12370, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31680479

RESUMO

INTRODUCTION: Stigma can be a barrier to early intervention of severe mental illnesses, especially schizophrenia, which further leads to poor outcomes. Mental health campaigns were designed to educate the general public about signs for early identification of psychosis, but the line between schizophrenia and attenuated psychosis was not well demarcated. We wonder if people would generalize their stigmas towards schizophrenia to subjects with subthreshold psychotic symptoms. METHODS: A cross-sectional survey was employed which used a structured questionnaire, comprised of four case vignettes describing attenuated psychosis syndrome (APS), schizophrenia, psychotic-like experiences (PLE), or depression, and was followed by two sets of questions using the 4-point Likert scale to measure discrimination and prejudices. Participants were chosen by convenience sampling of laypersons from different backgrounds. RESULTS: A total of 268 subjects completed this survey. A gradient of stigmas, highest toward schizophrenia, followed by APS/depression, and lowest toward PLE was apparent across gender, all age groups, and education levels. Participants who were younger and had higher education revealed a trend of lower prejudice and discrimination. People who have visited a psychiatric hospital showed higher discrimination toward schizophrenia, APS, and depression. People who have seen mentally ill persons in public places showed lower stigma toward PLE. DISCUSSION: Our respondents posed a differentiable attitude towards PLE, APS, and schizophrenia, while exhibiting no difference between APS and depression. Certain personal attributes were correlated with stigma levels. Further investigation about mental health literacy and attitudes towards subjects with psychotic symptoms in the general public is warranted.

8.
J Formos Med Assoc ; 119(1 Pt 3): 439-448, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31558338

RESUMO

BACKGROUND: This study aimed to examine social-cognitive impairments in patients with schizophrenia using the Eyes test. In contrast to previous methods using the correct answers, we developed the Taiwanese version of the Eyes test and constructed the response network to explore impairments in the emotional aspects of theory of mind in patients with schizophrenia. METHODS: Eighteen patients with schizophrenia and 18 healthy controls were recruited to examine their performance of the Eyes test. To explore the internal structures of mental states, we used network analysis to construct the networks of choice patterns (i.e. participants' answers) by using two network indicators, including density (an index of structure diversity of a network) and centrality (an index of the choice patterns within a network). Moreover, we divided all the choices into negative, positive, and neutral item groups based on emotion polarity. RESULTS: The patient group was slower and less accurate than the control group. Moreover, there was a negative correlation between accuracy and blunted affect, and there were positive correlations between reaction time and emotional withdrawal and apathetic social withdrawal. As compared to healthy controls, patients with schizophrenia showed larger density in the network structure and higher centrality than controls. Also, patients showed poorer performance on negative words than healthy controls. CONCLUSION: Our results demonstrated more diversity to recognize negative emotions from patients' choice patterns as compared to those in the control group. These findings suggest that deficits on recognizing negative emotions might be associated with the dysfunctions of mental states in schizophrenia.

9.
J Cardiovasc Electrophysiol ; 31(1): 9-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31808239

RESUMO

BACKGROUND: The management of refractory electrical storm (ES) requiring mechanical circulation support (MCS) remains a clinical challenge in structural heart disease (SHD). OBJECTIVE: The study sought to explore the 30-day and 1-year outcome of rescue ablation for refractory ES requiring MCS in SHD. METHODS: A total of 81 patients (mean age: 55.3 ± 18.9, 73 men [90.1%]) undergoing ablation were investigated, including 26 patients with ES requiring MCS (group 1) and 55 patients without (group 2). The 30-day and 1-year outcome, including mortality and recurrent ventricular tachyarrhythmias (VAs) receiving appropriate implantable cardioverter defibrillators therapies, were assessed. RESULTS: The patients in group 1 were characterized by older age, more ischemic cardiomyopathies, worse left ventricular ejection fraction, and more comorbidities. Thirty days after ablation, overall events were seen in 15 patients (mortality in 10 and recurrent VA in 7), including pumping failure-related mortality in 6 (60%). During a 30-day follow-up, higher mortality was noted in group 1. After a 1-year follow-up, in spite of the higher mortality in group 1 (P < .001), the overall events and VA recurrences were similar between these two groups (P = .154 and P = .466, respectively). There was a significant reduction of VA burden in both groups and two patients had recurrent ES. CONCLUSION: Higher 30-day mortality was observed in patients undergoing rescue ablation for refractory ES requiring MCS, and pumping failure was the major cause of periprocedural death. Rescue ablation successfully prevented VA recurrences and resulted in a comparable 1-year prognosis between ES with and without MCS.

10.
Heart Rhythm ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756530

RESUMO

BACKGROUND: Signal-averaged electrocardiogram (SAECG) provides not only diagnostic information but also the prognostic implication of ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC). OBJECTIVE: This study aimed to validate the role of SAECG in identifying arrhythmogenic substrates requiring an epicardial approach in ARVC. METHODS: Ninety-one patients with a definite diagnosis of ARVC who underwent successful ablation for drug-refractory ventricular arrhythmia were enrolled and classified into 2 groups: group 1 who underwent successful ablation at the endocardium only and group 2 who underwent successful ablation requiring an additional epicardial approach. The baseline characteristics of patients and SAECG parameters were obtained for analysis. RESULTS: Male predominance, worse right ventricular (RV) function, higher incidence of syncope, and depolarization abnormality were observed in group 2. Moreover, the number of abnormal SAECG criteria was higher in group 2 than in group 1. After a multivariate analysis, the independent predictors of the requirement of epicardial ablation included the number of abnormal SAECG criteria (odds ratio 2.8, 95% confidence interval 1.4-5.4; P = .003) and presence of syncope (odds ratio 11.7; 95% confidence interval 2.7-50.4; P = .001). In addition, ≥2 abnormal SAECG criteria were associated with larger RV endocardial unipolar low-voltage zone (P < .001), larger RV endocardial/epicardial bipolar low-voltage zone/scar (P < .05), and longer RV endocardial/epicardial total activation time (P < .001 and P = .004, respectively). CONCLUSION: The number of abnormal SAECG criteria was correlated with the extent of diseased epicardial substrates and could be a potential surrogate marker for predicting the requirement of epicardial ablation in patients with ARVC.

11.
Nat Genet ; 51(12): 1670-1678, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31740837

RESUMO

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Estudos de Casos e Controles , Extremo Oriente , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos
12.
J Comp Neurol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721208

RESUMO

Disrupted-in-Schizophrenia 1 (DISC1) is a susceptibility gene for several psychiatric illnesses. To study the pathogenesis of these disorders, we generated Disc1 mutant mice by introducing the 129S6/SvEv 25-bp deletion Disc1 variants into the C57BL/6J strain. In this study, we used heterozygous Disc1 mutant (Het) mice to evaluate the DISC1 haploinsufficiency model of schizophrenia. No changes in locomotor behaviors were observed in Het mice; however, after amphetamine injection, greater locomotor activity was observed in Het mice compared with wild-type (WT) mice. Moreover, amphetamine-induced elevations of c-Fos expression and dopamine level in the striatum were greater in Het mice than in WT controls, suggesting an altered dopaminergic regulation in the striatum of Het mice. Compared with those in WTs, the striatal protein levels of dopamine transporter and D2 dopamine receptor were increased in Het mice, while D1 dopamine receptor level was decreased. DISC1 interacting proteins, GSK3α and GSK3ß, were downregulated in Het mice, whereas the levels of PDE4B and CREB were not altered. Morphologically, the complexities of striatal median spiny neurons (MSNs), parvalbumin-positive interneurons and Iba1-positive microglia were all decreased in Het mice. The density and head diameter of dendritic spines in the MSNs of Het mice were also reduced. Our results indicate that mice lacking one WT Disc1 allele are more sensitive to psychostimulant amphetamine challenge, which might be attributed to the altered structure and function of the striatal dopaminergic system. Here, we demonstrated striatal phenotypes in heterozygous Disc1 mutant mice, which could be a promising model of DISC1 haploinsufficiency.

13.
J Clin Monit Comput ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468255

RESUMO

Adequate barrier pressure (BrP), calculated by subtracting intragastric pressure (IGP) from lower esophageal sphincter pressure (LESP), is believed to prevent gastroesophageal regurgitation (GER). However, the occurrence of intraoperative GER, the height and acidity it reached, have rarely been demonstrated simultaneously along with BrP. In this study, we developed preattached multichannel intraluminal impedance monitoring combined with pH-metry (the gold standard for detecting both height and acidity) on a solid-state manometry to continuously detect intraoperative GER as well as BrP changes. We used this system to record LESP, IGP, and changes in impedance through multichannel sensors and pH in patients receiving elective gynecological laparoscopy with laparoscopic pneumoperitoneum and Trendelenburg (LPT) positioning. Changes in BrP were analyzed at three time points (T1: before LPT; T2: during LPT when LESP reached its peak; and T3: after the offset of LPT). Our results indicated that this preattached experimental setup is feasible for intraoperative applications. GER was not detected in our patients throughout LPT. The mean LESP at T2 (23.22 mmHg) was significantly higher than at T1 (13.23 mmHg), but comparable to that at T3 (18.91 mmHg). The mean IGP (3.24 mmHg) at T2 was significantly higher than at T1 and T3 (- 6.10 and - 2.25 mmHg, respectively). The mean BrP scores were comparable from T1 to T3 (T1: 19.34 mmHg; T2: 19.98 mmHg; T3: 21.16 mmHg). Based on our results, the proposed setup is helpful for intraoperative monitoring and management of patients at high risk of GER.

14.
J Cardiovasc Electrophysiol ; 30(9): 1508-1516, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257650

RESUMO

BACKGROUND: Acute failure of radiofrequency ablation (RFA) of ventricular arrhythmias (VAs) occur in 10%-20% of patients and is partly attributed to inadequate lesion depth acquired with standard ablation protocols. Half-normal saline (HNS)-irrigation is a promising strategy to improve the success rate of VA ablation. OBJECTIVE: This study investigated the efficacy of HNS-irrigated ablation after a failed standard plain normal saline solution (PNSS)-irrigated ablation on idiopathic outflow tract ventricular arrhythmia (OT-VA). METHOD: This is a prospective observational study of consecutive patients undergoing RFA of idiopathic OT-VA comparing the efficacy of additional HNS-irrigated ablation for failed standard PNSS-irrigated ablation. Acute failure was defined as persistence of spontaneous VA or persistent inducibility of the clinical VA. RESULTS: Out of 160 OT-VA cases (51 ± 15-year-old, 62 males), 31 underwent HNS irrigation after a failed standard PNSS-irrigated ablation. The HNS group had a significantly longer procedure time (60.06 ± 43.83 vs 37.51 ± 33.40 minutes; P = .013) and higher radiation exposure (31.45 ± 20.24 vs 17.22 ± 15.25 minutes; P = .001) than the PNSS group but provided an additional acute success in 21 of 31 (67.7%) patients. Over a follow-up duration of 7.8 ± 4.6 months, 24 recurrences were identified, including 8 (25.8%) in the HNS and 16 (12.4%) in the PNSS group, with lower freedom from recurrence in the HNS group (log rank P = .009). No major complication was observed. CONCLUSION: HNS-irrigated ablation after failed standard PNSS-irrigated ablation is safe and additionally improves acute ablation success by 67.7% for idiopathic OT-VA but with a higher rate of recurrence on follow-up. Whether the application of HNS as initial irrigant could result in better outcome requires further investigation.

15.
J Cardiovasc Electrophysiol ; 30(8): 1215-1228, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148287

RESUMO

INTRODUCTION: We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with nonparoxysmal atrial fibrillation (AF). METHODS AND RESULTS: Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug-refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity-matched analysis (N = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95% confidence interval [95% CI], 1.63-10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09-3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16-5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08-0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17-0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups. CONCLUSION: Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia.

16.
Front Psychiatry ; 10: 223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037058

RESUMO

Background: Auditory event-related potentials (ERPs) have been utilized to study defective information processing of patients with schizophrenia. To delineate the pathophysiological processes from pre-psychotic state to first-episode psychosis, a study on subjects from ultra-high-risk (UHR) state to first-episode psychosis, ideally in an antipsychotic-free condition, can add important information to our understanding. Methods: Patients with UHR state or at their first-episode psychosis (FEP) who were drug-naive or only have been temporarily treated with antipsychotics were assessed by auditory ERPs measurement, including P50/N100 (sensory gating) and duration mismatch negativity (MMN; deviance detection). A group of age-matched healthy subjects served as their controls. Results: A total of 42 patients (23 UHR and 19 FEP) and 120 control subjects were recruited, including 21 pure drug-naive and 21 with very short exposure to antipsychotics. Collapsing FEP and UHR as a patient group, they exhibited significant sensory deficits manifested as larger P50 S2 amplitude, larger N100 ratio, and smaller N100 difference, and significantly less deviance detection response revealed by MMN. Such differences were less significant when treating FEP and UHR separately for comparisons. Comparisons of ERP results between drug-naive subjects and antipsychotic-short-exposure subjects revealed no significant difference in any P50/N100 and MMN parameter. Conclusion: Our study is one of the few studies focused on drug-naive or minimally treated patients at pre- or early-psychotic states. Our results exhibited impaired performance in sensory gating and deviance detection shown by certain parameters. A longitudinal study with larger sample sizes will be helpful to provide more evidence to elucidate the role of antipsychotics on an individual's neurophysiological performance at different stages of psychosis.

17.
J Hum Genet ; 64(7): 653-663, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30976040

RESUMO

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.


Assuntos
Proteínas do Tecido Nervoso/genética , Transtornos Neurocognitivos/genética , Esquizofrenia/genética , Alelos , Éxons , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Transtornos Neurocognitivos/metabolismo , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de RNA/genética , Isoformas de RNA/metabolismo , Esquizofrenia/metabolismo , Taiwan
18.
J Cardiovasc Electrophysiol ; 30(7): 1013-1025, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977218

RESUMO

AIMS: Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. METHODS: This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. RESULTS: A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. CONCLUSION: This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.

19.
Clin EEG Neurosci ; 50(4): 227-230, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30862179

RESUMO

Building on the knowledge of sex differences in auditory sensory gating in schizophrenia and hippocampal involvement in sensory gating, this study aimed to investigate sex as a potential moderator of the association between hippocampal volume and P50 in schizophrenia. Auditory P50 gating and hippocampal volume were measured in 16 male and 15 female patients with schizophrenia. The correlations between hippocampal volume and P50 were analyzed in males and females separately, corrected for potential confounders, including age, duration of illness, and antipsychotic medication. Different associative patterns of hippocampal volume with P50 gating ratio and with P50 difference were found by sex. The results suggest sex may play a role in the physiology of sensory gating.


Assuntos
Hipocampo/patologia , Hipocampo/fisiopatologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Filtro Sensorial/fisiologia , Caracteres Sexuais , Estimulação Acústica , Adulto , Percepção Auditiva/fisiologia , Potenciais Evocados , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Psicologia do Esquizofrênico
20.
Biol Psychiatry ; 86(1): 56-64, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30926130

RESUMO

BACKGROUND: Whether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium. METHODS: Among 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents' genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients' early onset of schizophrenia (≤18 years old) on paternal age was conducted. RESULTS: Advanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients' early onset of schizophrenia remained (odds ratio = 1.29, p = .04). CONCLUSIONS: The association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

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