Search

Although the phenomenon of attenuated niacin response (ANR) has been widely replicated in some patients with first-episode psychosis (FEP), its relevance to the negative symptoms (NS) of psychosis remains unclear. Total of 240 patients with drug-naïve FEP and 101 healthy controls (HCs) were recruited, and 209 were followed up for 1 year. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and niacin-induced responses were measured using laser Doppler flowmetry. We calculated the log-transform EC 50 [concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response] and MBF values. Core-NS was generated by factor analysis of the PANSS-NS subscale and cluster analysis to produce subtypes. Significant differences were found in the log 10 (EC 50 ) values between the FEP and HC groups (p < 0.001), supporting the ANR in patients with FEP. A higher NS severity was found in the ANR subgroup than that in other patients. Factor analysis determined that a two-dimensional model included core NS and rigidity of thinking. The log 10 (EC 50 ) value was significantly associated with only the core NS. Cluster analysis revealed three subtypes-36.7% (cluster-1, n = 88), 16.7% (cluster-2, n = 40), and 46.7% (cluster-3, n = 112). Cluster-2 characterized by extensive NS appeared to have a more remarkable ANR and less symptomatic improvement than those with other clusters during follow-up. No significant changes were found in the niacin response trajectories between the baseline and follow-up. Our findings indicate a significant correlation between ANR and core NS in patients with FEP. ANR may be a potential biomarker for certain subtypes with NS-dominated characteristics and poor symptomatic remission., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: Impaired sensitivity of the skin flush response to niacin is found in approximately 30% of patients with schizophrenia. Although the niacin response abnormality (NRA) may serve as a useful endophenotype for schizophrenia, few studies have directly replicated NRA in patients with first-episode psychosis (FEP)., Methods: In total, 204 patients with FEP, 16 with psychotic mood disorder (PMD), and 68 healthy controls (HC) were included. The log 10 (EC 50 ) values represent the concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response, and the MBF value was calculated. The NRA was defined as having log 10 (EC 50 ) molar value above the 90% and an MBF value below the 60% of those in the HC group., Results: In total, 13.7% of the FEP, 12.5% of the PMD, and 7.4% of the HC group met the definition of NRA. Significant differences were found in the log 10 (EC 50 ) values between the FEP and HC groups (p = .014) and in the MBF between the FEP and PMD groups (p = .011). Patients with FEP and NRA had more severe negative symptoms than those with a normal niacin response., Discussion: These data represent the NRA in patients with FEP, defining a small subgroup of patients with early-phase psychosis possessing a clinically significant phospholipid-signaling defect., (© 2022 John Wiley & Sons Australia, Ltd.)

The lack of objective diagnostic markers has long been a challenge in the clinical management of schizophrenia (SZ). The current bivariate cut-offs method is an objective quantification of niacin skin flush abnormality (NFA) for identifying the SZ subgroup. However, the sensitivity of approximately 30% limits the application of NFA as a marker for detecting SZ. A laser Doppler flowmeter was employed to test the niacin skin-flushing response in 123 patients with first-episode psychosis including first-episode SZ (FES, n = 82) and psychotic bipolar disorders (PBP, n = 41), and non-psychiatric comparisons (NPC, n = 80). We modified the bivariate cut-offs using a combination of the niacin concentration corresponding to the half-maximal blood flow response (EC 50 ) and a new quantitative indicator called the overall trend area (OTA). The NFA used this study method predicted FES in the NPC group with 57% sensitivity, 89% specificity, and 73% accuracy compared to the 28% sensitivity, 91% specificity, and 59% accuracy of the existing method. This novel method could discern FES from the PBP group with an accuracy of 62%, compared with the 45% of the old method. In addition, we also discuss whether the bivariate cut-offs were occasional by adjusting the cut-offs threshold. The experimental results showed that the sensitivity and specificity were most stable when using the study method. The study indicates that NFA using modified bivariate cut-offs may be a potential objective marker in FES, and the niacin skin test could be feasible for early diagnosis and treatment of SZ., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Individuals at clinical high risk (CHR) for psychosis exhibit a reduced P300 oddball response, which indicates deficits in attention and working memory processes. Previous studies have mainly researched these responses in the temporal domain; hence, non-phase-locked or induced neural activities may have been ignored. Event-related potential (ERP) and time-frequency (TF) information, combined with clinical and cognitive profiles, may provide an insight into the pathophysiology and psychopathology of the CHR stage. The 104 CHR individuals who completed cognitive assessments and ERP tests were recruited and followed up between 2016 and 2018. Individuals with CHR were classified by three clinical subtypes demonstrated before, specifically 32 from Cluster-1 (characterized by extensive negative symptoms and cognitive deficits, at the highest risk for conversion to psychosis), 34 from Cluster-2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 38 from Cluster-3 (characterized by the mildest symptoms and cognitive deficits). Electroencephalograms were recorded during the auditory oddball paradigm. The P300 ERPs were analyzed in the temporal domain. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired by TF analysis. A reduced P300 response to target tones was noted in Cluster-1 relative to the other two clusters. Moreover, the P300 amplitude of Cluster-1 was associated with speed of processing (SoP) scores. Furthermore, the P300 amplitude of Cluster-3 was significantly correlated with verbal and visual learning scores. In the TF analysis, decreased delta ERSP and ITC were observed in Cluster-1; delta ITC was associated with SoP scores in Cluster-3. The results indicate relatively disrupted oddball responses in a certain CHR subtype and a close affinity between these electrophysiological indexes and attention, working memory, and declarative memory within different CHR clusters. These findings suggest that the auditory oddball response is a potential neurophysiological marker for distinct clinical subtypes of CHR., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Current treatment guidelines for individuals at clinical high risk (CHR) for psychosis do not recommend the prescription of antipsychotics (not even second-generation ones) as the first treatment option for preventing psychosis. Yet, recent meta-analytic evidence indicates that antipsychotic exposure in CHR is relatively widespread and associated with a higher imminent risk of transition to psychosis. Therefore, we undertook this study to better delineate which clinical characteristics of CHR individuals may lead to the choice of antipsychotic prescription and whether it identifies a subgroup at higher risk for conversion to psychosis., Methods: Consecutively referred CHR individuals (N = 717) were assessed for demographic and clinical characteristics and followed up for 3 years (200 did not reach the end of the follow-up time) from 2016 to 2021. The sample was then dichotomized, on the basis of antipsychotic prescription, to prescribed (CHRAP+, n = 492) or not-prescribed (CHRAP-, n = 225) groups, which were subsequently compared for sociodemographic and clinical characteristics. The risks of conversion to psychosis in CHRAP+ versus CHRAP- groups were tested via survival analysis., Results: Of the 717 CHR individuals, 492 (68.62%) were prescribed antipsychotics; among these antipsychotics, the highest proportion used was for aripiprazole (n = 152), followed by olanzapine (n = 106), amisulpride (n = 76), and risperidone (n = 64). The CHRAP+ group had younger age ( t  = 2.138, P  = .033), higher proportion of female individuals ( χ 2  = 5.084, P  = .024), psychotic symptoms of greater severity ( t  = 7.910, P  < .001), and more impaired general function ( t  = 5.846, P  < .001) than the CHRAP- group. The CHRAP+ group had greater risk for conversion to psychosis (27.0% in the CHRAP+ group vs 10.9% in the CHRAP- group, P  < .001). Factors related to positive symptoms were the most likely to influence doctors' decision-making regarding prescripton of antipsychotics, without influence of age, sex, and education levels., Conclusions: Clinicians may prescribe antipsychotics mainly based on the severity of positive and disorganization symptoms of CHR individuals. The CHRAP+ group was associated with a higher risk of conversion to psychosis. In pragmatic terms, this finding indicates that baseline antipsychotic prescription in CHR cohorts is a warning flag for higher incipient risk of psychosis and designates as hyper-CHR subgroup as compared to antipsychotic-naive CHR., Trial Registration: ClinicalTrials.gov identifier: NCT04010864., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Background: Age effects may be important for improving models for the prediction of conversion to psychosis for individuals in the clinical high risk (CHR) state. This study aimed to explore whether adolescent CHR individuals (ages 9-17 years) differ significantly from adult CHR individuals (ages 18-45 years) in terms of conversion rates and predictors., Method: Consecutive CHR individuals ( N = 517) were assessed for demographic and clinical characteristics and followed up for 3 years. Individuals with CHR were classified as adolescent ( n = 244) or adult ( n = 273) groups. Age-specific prediction models of psychosis were generated separately using Cox regression., Results: Similar conversion rates were found between age groups; 52 out of 216 (24.1%) adolescent CHR individuals and 55 out of 219 (25.1%) CHR adults converted to psychosis. The conversion outcome was best predicted by negative symptoms compared to other clinical variables in CHR adolescents (χ 2 = 7.410, p = 0.006). In contrast, positive symptoms better predicted conversion in CHR adults (χ 2 = 6.585, p = 0.01)., Conclusions: Adolescent and adult CHR individuals may require a different approach to early identification and prediction. These results can inform the development of more precise prediction models based on age-specific approaches.