RESUMO
OBJECTIVE: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. METHODS: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. RESULTS: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. CONCLUSION: Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.
RESUMO
OBJECTIVE: Extrapyramidal symptoms (EPS) are common side effects of antipsychotic drugs. Despite the growing interest in exploring objective biomarkers for EPS prevention and the potential use of voice in detecting clinical disorders, no studies have demonstrated the relationships between vocal changes and EPS. Therefore, we aimed to determine the associations between voice changes and antipsychotic dosage, and further investigated whether speech characteristics could be used as predictors of EPS. METHODS: Forty-two patients receiving or expected to receive antipsychotic drugs were recruited. Drug-induced parkinsonism of EPS was evaluated using the Simpson-Angus Scale (SAS). Participants' voice data consisted of 16 neutral sentences and 2 second-long /Ah/utterances. Thirteen voice features were extracted from the obtained voice data. Each voice feature was compared between groups categorized based on SAS total score of below and above "0.6." The associations between antipsychotic dosage and voice characteristics were examined, and vocal trait variations according to the presence of EPS were explored. RESULTS: Significant associations were observed between specific vocal characteristics and antipsychotic dosage across both datasets of 1-16 sentences and /Ah/utterances. Notably, Mel-Frequency Cepstral Coefficients (MFCC) exhibited noteworthy variations in response to the presence of EPS. Specifically, among the 13 MFCC coefficients, MFCC1 (t=-4.47, p<0.001), MFCC8 (t=-4.49, p<0.001), and MFCC12 (t=-2.21, p=0.029) showed significant group differences in the overall statistical values. CONCLUSION: Our results suggest that MFCC may serve as a predictor of detecting drug-induced parkinsonism of EPS. Further research should address potential confounding factors impacting the relationship between MFCC and antipsychotic dosage, possibly improving EPS detection and reducing antipsychotic medication side effects.
RESUMO
Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.
Assuntos
Transtornos Psicóticos , Humanos , Masculino , Feminino , Estudos Longitudinais , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/epidemiologia , Adulto Jovem , Adulto , Transtorno Autístico/fisiopatologia , Transtorno Autístico/epidemiologia , Esquizofrenia/fisiopatologia , Esquizofrenia/epidemiologia , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Adolescente , República da Coreia/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , ComorbidadeRESUMO
Constructing pertinent nanoarchitecture with abundant exposed active sites is a valid strategy for boosting photocatalytic hydrogen generation. However, the controllable approach of an ideal architecture comprising vertically standing transition metal chalcogenides (TMDs) nanosheets on a 3D graphene network remains challenging despite the potential for efficient photocatalytic hydrogen production. In this study, we fabricated edge-rich 3D structuring photocatalysts involving vertically grown TMDs nanosheets on a 3D porous graphene framework (referred to as 3D Gr). 2D TMDs (MoS2 and WS2)/3D Gr heterostructures were produced by location-specific photon-pen writing and metal-organic chemical vapor deposition for maximum edge site exposure enabling efficient photocatalytic reactivity. Vertically aligned 2D Mo(W)S2/3D Gr heterostructures exhibited distinctly boosted hydrogen production because of the 3D Gr caused by synergetic impacts associated with the large specific surface area and improved density of exposed active sites in vertically standing Mo(W)S2. The heterostructure involving graphene and TMDs corroborates an optimum charge transport pathway to rapidly separate the photogenerated electron-hole pairs, allowing more electrons to contribute to the photocatalytic hydrogen generation reaction. Consequently, the size-tailored heterostructure showed a superior hydrogen generation rate of 6.51 mmol g-1 h-1 for MoS2/3D graphene and 7.26 mmol g-1 h-1 for WS2/3D graphene, respectively, which were 3.59 and 3.76 times greater than that of MoS2 and WS2 samples. This study offers a promising path for the potential of 3D structuring of vertical TMDs/graphene heterostructure with edge-rich nanosheets for photocatalytic applications.
RESUMO
BACKGROUND: Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders. METHODS: The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders. RESULTS: The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5-77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4-46.4), 52.4% (95% CI 28.1-81.1), 66.7% (95% CI 24.6-98.6) and 54.3% (95% CI 20.5-93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8-11.5), 45.7% (95% CI 24.4-73.6), and 11.2% (95% CI 3.1-36.2), respectively. CONCLUSIONS: Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma.
Assuntos
Transtornos Psicóticos , Humanos , Feminino , Masculino , Adulto , Transtornos Psicóticos/epidemiologia , Adulto Jovem , Adolescente , Transtorno Bipolar/epidemiologia , Estudos Longitudinais , Estudos Prospectivos , Transtornos Mentais/epidemiologia , Progressão da Doença , Transtorno Depressivo/epidemiologia , Sintomas ProdrômicosRESUMO
Delay discounting (DD), a parameter derived from the intertemporal choice task, is a representative behavioral indicator of choice impulsivity. Previous research reported not only an association between DD and impulsive control disorders and negative health outcomes but also the neural correlates of DD. However, to date, there are few studies investigating the structural brain network topologies associated with individual differences in DD and whether self-reported measures (BIS-11) of impulsivity associated with DD share the same or distinct neural mechanisms is still unclear. To address these issues, here, we combined graph theoretical analysis with diffusion tensor imaging to investigate the associations between DD and the topological properties of the structural connectivity network and BIS-11 scores. Results revealed that people with a steep DD (greater impatience) had decreased small-worldness (a shift toward weaker small-worldnization) and increased degree centrality in the medial superior prefrontal cortex, associated with subjective value in the task. Though DD was associated with the BIS-11 motor impulsiveness subscale, this subscale was linked to topological properties different from DD; that is, high motor impulsiveness was associated with decreased local efficiency (less segregation) and decreased degree centrality in the precentral gyrus, involved in motor control. These findings provide insights into the systemic brain characteristics underlying individual differences in impulsivity and potential neural markers which could predict susceptibility to impulsive behaviors.
Assuntos
Imagem de Tensor de Difusão , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imageamento por Ressonância Magnética , Comportamento Impulsivo , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Childhood maltreatment is a risk factor for the development of post-traumatic stress disorders and psychosis. However, the association between post-traumatic stress disorder (PTSD), including complex PTSD, and psychotic symptoms is unknown. We investigated whether the presence of PTSD and complex PTSD was associated with psychotic symptom severity within survivors of developmental trauma. METHODS: As part of the Investigating Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT) study, from Aug 20, 2020, to Jan 24, 2021, and from Sept 9, 2022, to Feb 21, 2023, using study advertisement on online platforms we recruited adult (≥18 years) participants who had experienced developmental trauma without a psychiatric diagnosis in the UK and South Korea. We measured whether participants met diagnostic thresholds for PTSD and complex PTSD using the self-reported International Trauma Questionnaire, and psychotic symptoms using the self-reported Community Assessment of Psychic Experiences. We used linear regression, adjusting for sociodemographic variables such as age, sex, ethnicity, educational attainment, and socioeconomic status, to examine whether there was an association between PTSD and complex PTSD and psychotic symptoms. The study is registered in the UK (University College London Research Ethics Committee [14317/001] and the National Health Service Research Ethics Committee [22/YH/0096]) and South Korea (Institutional Review Board of Seoul National University Bundang Hospital [B-2011-648-306]), and is ongoing. FINDINGS: Of the 2675 participants who took part in the study, 1273 had experienced developmental trauma and were included in the study in the UK (n=475) and South Korea (n=798), comprising 422 (33%) men and 851 (67%) women with a mean age of 26·9 years (SD 6, range 18-40), mostly of White British (n=328) or South Korean (n=798) ethnicity. We found no significant association between PTSD and psychotic symptom severity (total severity ß=-2·40 [SE 3·28], p=0·47), compared with participants who did not meet PTSD or complex PTSD caseness. We found a significant relationship between complex PTSD and psychotic symptom severity (total severity ß=22·62 [SE 1·65], p<0·0001), including for positive (ß=12·07 [SE 0·99], p<0·0001) and negative symptoms (ß=10·5 [SE 0·95], p<0·0001), compared with participants who did not meet PTSD or complex PTSD caseness. INTERPRETATION: Health systems must assess individuals with previous developmental trauma for complex PTSD and treat those affected. These individuals should also be assessed for psychotic symptoms, and if necessary, preventative measures should be taken to reduce risk of conversion. Further work should assess whether treating complex PTSD modifies the risk of conversion to psychosis. FUNDING: UKRI Future Leaders Fellowship, British Medical Association Margaret Temple Award for Schizophrenia Research, and the National Research Foundation of Korea-Korea Government.
Assuntos
Transtornos Psicóticos , Transtornos de Estresse Pós-Traumáticos , Masculino , Adulto , Feminino , Humanos , Adolescente , Adulto Jovem , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estudos Transversais , Medicina Estatal , Transtornos Psicóticos/epidemiologia , República da Coreia/epidemiologia , Reino Unido/epidemiologiaRESUMO
Introduction: People prefer immediate over future rewards because they discount the latter's value (a phenomenon termed "delay discounting," used as an index of impulsivity). However, little is known about how the preferences are implemented in brain in terms of the coordinated pattern of large-scale structural brain networks. Methods: To examine this question, we classified high discounting group (HDG) and low discounting group (LDG) in young adults by assessing their propensity for intertemporal choice. We compared global and regional topological properties in gray matter volume-based structural covariance networks between two groups using graph theoretical analysis. Results: HDG had less clustering coefficient and characteristic path length over the wide sparsity range than LDG, indicating low network segregation and high integration. In addition, the degree of small-worldness was more significant in HDG. Locally, HDG showed less betweenness centrality (BC) in the parahippocampal gyrus and amygdala than LDG. Discussion: These findings suggest the involvement of structural covariance network topology on impulsive choice, measured by delay discounting, and extend our understanding of how impulsive choice is associated with brain morphological features.
RESUMO
OBJECTIVE: The Community Assessment of Psychic Experiences has been widely translated and commonly used as a measure for psychotic experiences and psychosis proneness in clinical and research environments worldwide. This study aimed to establish the psychometric properties (reliability and validity) and factor structure of a Korean version of the Community Assessment of Psychic Experiences (K-CAPE) in the general population. METHODS: A total of 1,467 healthy participants completed K-CAPE and other psychiatric symptom-related scales (Paranoia scale, Patient Health Questionnaire-9, Dissociative Experiences Scale-II, and Oxford-Liverpool Inventory of Feelings and Experiences) via online survey. K-CAPE's internal reliability was analyzed using Cronbach's alpha coefficient. Confirmatory factor analysis (CFA) was performed to investigate whether the original three-factor model (positive, negative, and depressive) and other hypothesized multidimensional models (including positive and negative subfactors) were suitable for our data. Exploratory factor analysis (EFA) was conducted to explore better alternative factor solutions with a follow-up CFA. To assess convergent and discriminant validity, we examined correlations between K-CAPE subscales with other established measures of psychiatric symptoms. RESULTS: K-CAPE showed good internal consistency in all original three subscales (all greater than α=0.827). The CFA demonstrated that the multidimensional models exhibited relatively better quality than the original three-dimensional model. Although the model fit indices did not reach their respective optimal thresholds, they were within an acceptable range. Results from the EFA indicated 3-5 factor solutions. In 3-factor solution, "negative-avolition" items were founded to be loaded more consistently with depressive items than with the negative dimension. In 4-factor solution, positive items were divided into two subfactors: "positive-bizarre experiences" and "positive-delusional thoughts," while negative symptoms were separated into two distinct subfactors in 5-factor solution: "negative-avolition (expressive)," and "negative-social (experiential)." The correlation coefficients between K-CAPE subscales and corresponding measurements were significant (p<0.001), confirming the convergent and discriminant validity. CONCLUSION: Our study provides evidence to support the reliability and validity of the K-CAPE and its use as a measure of psychotic symptoms in the Korean population. Although alternative factor structures did not improve the model fit, our EFA findings implicate the use of subfactors to investigate more specific domains of positive and negative symptoms. Given the heterogeneous nature of psychotic symptoms, this may be useful in capturing their different underlying mechanisms.
RESUMO
In this study we evaluate the performance of a fully automated analytical framework for FDOPA PET neuroimaging data, and its sensitivity to demographic and experimental variables and processing parameters. An instance of XNAT imaging platform was used to store the King's College London institutional brain FDOPA PET imaging archive, alongside individual demographics and clinical information. By re-engineering the historical Matlab-based scripts for FDOPA PET analysis, a fully automated analysis pipeline for imaging processing and data quantification was implemented in Python and integrated in XNAT. The final data repository includes 892 FDOPA PET scans organized from 23 different studies. We found good reproducibility of the data analysis by the automated pipeline (in the striatum for the Kicer: for the controls ICC = 0.71, for the psychotic patients ICC = 0.88). From the demographic and experimental variables assessed, gender was found to most influence striatal dopamine synthesis capacity (F = 10.7, p < 0.001), with women showing greater dopamine synthesis capacity than men. Our automated analysis pipeline represents a valid resourse for standardised and robust quantification of dopamine synthesis capacity using FDOPA PET data. Combining information from different neuroimaging studies has allowed us to test it comprehensively and to validate its replicability and reproducibility performances on a large sample size.
Assuntos
Di-Hidroxifenilalanina , Dopamina , Masculino , Humanos , Feminino , Dopamina/metabolismo , Reprodutibilidade dos Testes , Tomografia por Emissão de Pósitrons/métodos , NeuroimagemRESUMO
We successfully demonstrated the improvement and stabilization of the electrical properties of a graphene field effect transistor by fabricating a sandwiched amorphous boron nitride (a-BN)/graphene (Gr)/a-BN using a directly grown a-BN film. The a-BN film was grown via low-pressure chemical vapor deposition (LPCVD) at a low growth temperature of 250 °C and applied as a protection layer in the sandwiched structure. Both structural and chemical states of the as-grown a-BN were verified by various spectroscopic and microscopic analyses. We analyzed the Raman spectra of Gr/SiO2 and a-BN/Gr/a-BN structures to determine the stability of the device under exposure to ambient air. Following exposure, the intensity of the 2D/G-peak ratio of Gr/SiO2 decreased and the position of the G and 2D peaks red-shifted due to the degradation of graphene. In contrast, the peak position of encapsulated graphene is almost unchanged. We also confirmed that the mobility of a-BN/Gr/a-BN structure is 17,941 cm2/Vs. This synthetic strategy could provide a facile way to synthesize uniform a-BN film for encapsulating various van der Waals materials, which is beneficial for future applications in nanoelectronics.
RESUMO
OBJECTIVE: The Positive and Negative Syndrome Scale (PANSS) is commonly used to assess the severity of the clinical symptoms of schizophrenia (SCZ). This study aimed to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model based on therapeutic drug monitoring (TDM) data to characterize the relationship between clozapine exposure and the PANSS scores in patients with SCZ. METHODS: TDM data for clozapine and PANSS scores from 45 patients with SCZ were included in this modeling analysis using NONMEM. Based on published data, intensive PK sampling data collected up to 12 hours postdose from 23 patients was incorporated into the PK data set to improve the fitting of absorption and disposition. For PD model development, the PANSS score was assessed at baseline, followed by 8 and 18 weeks after the initiation of clozapine dosing. Visual predictive check plots, the precision of parameter estimates, and decreases in the minimum objective function values were used for the model evaluation. RESULTS: A 2-compartment model with an absorption lag and a combined error model adequately described the PK of clozapine. The implementation of disease progression with placebo and drug effects improved the model's ability to describe the time course of the PANSS scores. In the final PK/PD model, Weibull and maximum effect (E max ) models were selected as disease progression models for the placebo and drug effect models, respectively. The model evaluation results supported the adequacy of the final model. CONCLUSIONS: A clozapine PK/PD model based on clinical settings adequately described the PANSS time course in patients with SCZ. These findings may aid the development of treatment strategies for patients with SCZ.
Assuntos
Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Clozapina/uso terapêutico , Antipsicóticos/uso terapêutico , Antipsicóticos/farmacocinética , Monitoramento de Medicamentos , Esquizofrenia/tratamento farmacológico , Fatores de TempoRESUMO
A 61-year-old man presented with abdominal distension without any symptoms. On colonoscopy and computed tomography findings, it was clinically diagnosed as peritoneal metastasis of sigmoid colon cancer, and diagnostic laparoscopy was performed. Only the peritoneum was partially resected, and the pathology was signet ring cell carcinoma with predominantly local mucinous carcinoma component. However, the patient complained of persistent symptoms and, despite the progress of chemotherapy, the peritoneal dissemination worsened, and additional cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) was performed. Mixed adenoneuroendocrine carcinomas (MANECs) were reported in the appendix with perforated visceral peritoneum. After additional chemotherapy, the patient was discharged. Patients with advanced MANEC with peritoneal spreading may benefit from aggressive treatment by cytoreduction surgery with HIPEC, followed by intravenous chemotherapy.
RESUMO
In the present study, various outcomes over 3-year period in patients with early stage psychosis including remission, recovery, relapse and medication adherence were investigated. Predictor for full recovery at year 3 was also examined. Three-year follow-up data in 534 patients with schizophrenia spectrum disorders (SSD) and psychotic disorder not otherwise specified (PNOS) were examined for overall outcome trajectories. The data of completers at year 3 (n = 157) were used to identify predictors for recovery using logistic regression. The rates of symptomatic remission and full recovery at 6-, 12-, 24-, and 36-month follow-up were 76.10, 69.20, 79.50, and 79.10%, and 22.80, 26.40, 28.60, and 39.60%, respectively. The rates of drop-out and relapse at 6-, 12-, 24-, and 36-month follow-up were 25.4, 29.5, 38.6, and 51.1%, and 3.7, 8.9, 19.0, and 38.9%, respectively. The rates of good adherence and prescription of Long-Acting Injectable Antipsychotics (LAIA) at 6-, 12-, 24- and 36-month follow-up were 87.8, 88.0, 91.9, and 93.9%, and 18.3, 21.7, 22.0, and 25.5%, respectively. Significant predictors for full recovery were duration of untreated psychosis (DUP), family intimacy and physical activity. We observed similar or better results on remission, recovery, and relapse rates compared to other previous studies. Effective psychosocial intervention should be provided to shorten the gap between remission and recovery rates and to address DUP, family issues, and exercise to enhance recovery.
RESUMO
Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe2 field-effect transistors (FETs), thereby enhancing the electric performance and stability of the device, accompanied with the suppression of chemical disorder at the HC/TMDCs interface. The stacking of HC onto MoSe2 FETs enhances the carrier mobility of MoSe2 FET by over 50% at the n-branch, and a significant decrease in hysteresis, owing to the screening of molecular adsorption. The electron mobility and hysteresis of the HC/MoSe2 FETs are verified to be nearly intact compared to those of the fabricated HC/MoSe2 FETs after exposure to ambient environment for 3 months. Consequently, the proposed design can act as a model for developing advanced nanoelectronics applications based on layered materials for mass production.
RESUMO
Objectives: Dopamine receptor D2 gene (DRD2) and glucocorticoid receptor gene (NR3C1) are implicated in the development of psychosis. We investigated methylation levels of DRD2 and NR3C1 in peripheral blood of patients with recent-onset (RO) psychosis using bisulfite pyrosequencing as well as its association with childhood trauma and rumination. Methods: In all, 51 individuals with RO psychosis and 47 healthy controls were recruited. DNA methylation levels in the targeted regions of two genes were analyzed and compared. Childhood trauma and rumination were evaluated using the Early Trauma Inventory Self-Report Short Form (ETI-SF) and Brooding Scale (BS), respectively. Correlations between the scores of the ETI-SF and BS and methylation levels were explored. Results: For DRD2, we found no significant differences between groups in terms of methylation level or association with childhood trauma or rumination. For NR3C1, we found a trend level significance for average value of all CpG sites and significant hypermethylation or hypomethylation at specific sites. There was also a significant positive correlation between the methylation level at the CpG8 site of NR3C1 exon 1F and negative symptom subscale score of the PANSS (PANSS-N). Conclusion: Epigenetic alterations of NR3C1 are associated with the pathophysiology of psychosis. Further epigenetic studies will elucidate the molecular mechanisms underpinning the pathophysiology of psychosis.
Assuntos
Metilação de DNA , Transtornos Psicóticos , Receptores de Dopamina D2 , Receptores de Glucocorticoides , Metilação de DNA/genética , Metilação de DNA/fisiologia , Epigênese Genética , Humanos , Transtornos Psicóticos/genética , Transtornos Psicóticos/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMO
OBJECTIVE: Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC). METHODS: Twenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant Kicer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Kicer and FA in each group were evaluated using Spearman's rho correlation coefficients. RESULTS: Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384). CONCLUSION: Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.
RESUMO
The dopamine blockade by antipsychotics trigger subjective dysphoria. Compared with D2 antagonists, aripiprazole, a D2 partial agonist, was expected to produce a different experience. Indeed, a previous study reported no relationship between the D2 receptor occupancy by aripiprazole and subjective dysphoria, while the D2 receptor occupancy by antagonists was associated with negative subjective experiences. This study revisited the relationship in patients treated with aripiprazole by using an inhibitory Emax model, which enables the individual drug-free binding potential and D2 receptor occupancy to be properly estimated. Eight patients with schizophrenia who have been clinically stable on aripiprazole were enrolled. Assessments including Positive and Negative Syndrome Scale (PANSS) and Subjective Well-being under Neuroleptics Scale (Kv-SWN) were administered. [11C]raclopride PET scan were conducted 2, 26, and 74 h after aripiprazole administration. Regression analysis showed a significant negative association between the D2 receptor occupancy by aripiprazole in the striatum and the Kv-SWN (R2 = 0.55, p = 0.036), but the PANSS total score was not associated with the Kv-SWN (R2 = 0.42, p = 0.080). The negative association between D2 receptor occupancy by aripiprazole and subjective well-being implies that clinicians should find the lowest effective doses of aripiprazole for clinically stable patients to improve their subjective experiences and clinical outcomes.
Assuntos
Antipsicóticos , Antipsicóticos/metabolismo , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Aripiprazol/farmacologia , Humanos , Tomografia por Emissão de Pósitrons , Racloprida/metabolismo , Receptores de Dopamina D2/metabolismoRESUMO
OBJECTIVE: Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). METHODS: We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the "population proportion" (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). RESULTS: We first constructed the "K-PERS-I," comprising five factors based on the PPS, and then the "K-PERS-II" comprising six factors based on the ERS. The instruments accurately predicted participants' status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. CONCLUSION: The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.
RESUMO
AIM: Research on psychotic disorder not otherwise specified (PNOS) that clearly mentions its subgroups is very rare. This study was conducted to identify the demographic and clinical features, cognitive function, and 1-year outcomes of patients with early stage PNOS compared with those with early stage schizophrenia (SZ). METHODS: The study subjects were 54 and 321 patients with PNOS and SZ, respectively, who were registered at least more than 1 year ago. Due to drop out, only 37 and 210 patients with PNOS and SZ were evaluated at the 1-year follow-up. We compared clinical variables (duration of untreated psychosis, symptom severity, self-rating scales, and so on), cognitive function, and short-term outcomes (treatment response, remission, compliance, drop out, relapse) between the two groups. RESULTS: The patients with PNOS were associated with higher diagnostic stability (53.7%) compared with those in previous studies. They had lower symptom severity, better treatment response at 2 months and higher remission rates at 12 months, but poorer compliance at 6 months compared with patients with SZ. Level of cognitive impairment in PNOS was intermediate between those of SZ patients and healthy controls. CONCLUSIONS: These findings indicate that PNOS has unique clinical features, suggesting that it should be treated as a distinct clinical syndrome. At the same time, however, prevention of its possible progression to other psychotic disorders in some patients with PNOS is also important.