Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

Calcium administration appears not to benefit acute pancreatitis patients with hypocalcemia.

OBJECTIVE: Hypocalcemia occurs commonly among patients with acute pancreatitis (AP) in the intensive care unit (ICU). Calcium therapy could be used to correct hypocalcemia and maintain calcium levels, but its impact on the prognosis has not been demonstrated. Our study aimed to determine whether calcium therapy could benefit the multiple outcomes of AP patients with hypocalcemia. METHODS: We extracted 807 AP patients with hypocalcemia from the Beth Israel Deaconess Medical Center (MIMIC-IV) database and performed retrospective analyses. The outcomes were in-hospital, 28 days, ICU mortality, and the length of stay (LOS) in the hospital and ICU. We performed propensity matching (PSM) and inverse probability weighting (IPTW) to balance the baseline differences and conducted multivariate regression to investigate the impact of calcium therapy. RESULTS: A total of 620 patients (76.8%) received calcium treatment (calcium group) during hospitalization, while 187 patients (non-calcium group) did not. Patients in the calcium group did not present significant survival differences between groups before and after matching. After including covariates, calcium administration had no association with patients' in-hospital (HR: 1.03, 95% Cl: 0.47-2.27, p = .942), 28 days and ICU mortality and was significantly associated with prolonged length of stay in the hospital (effect estimate: 6.18, 95% Cl: 3.27-9.09, p < .001) and ICU (effect estimate: 1.72, 95% Cl: 0.24-3.20, p < .001). Calcium therapy could not benefit patients in subgroups with exclusive parenteral infusion, early calcium therapy (<48 h), or various degrees of hypocalcemia. CONCLUSION: AP patients with hypocalcemia could not benefit from calcium administration, which has no association with multiple mortality and is significantly associated with prolonged LOS in the hospital and ICU.

Absolute CO2 /Xenon Separation in Ultramicropore MOF for Anesthetic Gases Regeneration.

Xe is an ideal anesthetic gas, but it has not been widely used in practice due to its high cost and low output. Closed-circuit Xe recovery and recycling is an economically viable method to ensure adequate supply in medical use. Herein, we design an innovative way to recover Xe by using a stable fluorinated metal-organic framework (MOF) NbOFFIVE-1-Ni to eliminate CO2 from moist exhaled anesthetic gases. Unlike other Xe recovery MOFs with low Xe/CO2 selectivity (less than 10), NbOFFIVE-1-Ni could achieve absolute molecular sieve separation of CO2 /Xe with excellent CO2 selectivity (825). Mixed-gas breakthrough experiments assert the potential of NbOFFIVE-1-Ni as a molecular sieve adsorbent for the effective and energy-efficient removal of carbon dioxide with 99.16 % Xe recovery. Absolute CO2 /Xe separation in NbOFFIVE-1-Ni makes closed-circuit Xe recovery and recycling can be easily realized, demonstrating the potential of NbOFFIVE-1-Ni for important anesthetic gas regeneration under ambient conditions.

Dispersing LiCl in Zwitterionic COF for Highly Efficient Ammonia Storage and Separation.

Efficient and inherently safe NH3 storage and separation are of significant importance for the chemical industry. Herein, we proposed zwitterionic COF as a porous host to disperse LiCl for highly efficient NH3 storage and separation with record adsorption capacity. The equivalently cationic and anionic groups in the channels of zwitterionic COF could act as two separated sites to facilitate the dispersion of LiCl, hence the optimal composite exhibits a high capture capacity of 44.98 mmol/g at 25 °C and 1 bar, far exceeding other existing porous materials. Notably, the adsorption capacity is completely reversible and the efficient separation of NH3 from NH3 /CO2 /N2 mixture is achieved through breakthrough experiments. DFT calculation combined with XPS and 7 Li NMR experimental results give insight into the interaction between zwitterionic COF and LiCl. This work extends possibilities for the development of efficient adsorbents for NH3 storage and separation.

Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Introduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

Association of Attenuated Niacin Response With Inflammatory Imbalance and Prediction of Conversion to Psychosis From Clinical High-risk Stage.

Objective: Attenuated niacin responses and changes in cytokine levels have been reported in schizophrenia. However, prior studies have typically focused on schizophrenia, and little is known about the association between niacin response and inflammatory imbalance in clinically high-risk psychosis (CHR). This study aimed to assess the niacin response to inflammatory imbalance for association with conversion to psychosis within 2 years.Methods: A prospective case-control study was performed to assess the niacin response and interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels in 60 CHR individuals and 60 age- and sex-matched healthy controls (HC) from May 2019 to December 2021. Participants with CHR were identified using the Structured Interview for Prodromal Syndromes. The niacin-induced responses were measured using laser Doppler flowmetry. From the dose-response curves, the log-transferred concentration of methylnicotinate required to elicit a half-maximal blood flow response (LogEC50) and maximal minus minimal blood flow response (Span) values were calculated for each subject. Serum cytokine levels were measured using enzyme-linked immunosorbent assay. Individuals with CHR were then divided into converters (CHR-C, n = 15) and non-converters (CHR-NC, n = 45) to psychosis based on their 2-year follow-up clinical status.Results: The CHR group exhibited significantly higher LogEC50 (t = 3.650, P < .001) and Span (t = 2.657, P = .009) values than the HC group. The CHR-C group exhibited a significantly shorter Span (t = 4.027, P < .001) than the CHR-NC group. The LogEC50 showed a trend toward significance (t = 1.875, P = .066). None of the cytokine levels were significant. The conversion outcome can therefore be predicted by applying LogEC50 (P = .049) and Span (P < .001). The regression model with variables of LogEC50, Span, family history, and scores of positive symptoms showed good discrimination of subsequent conversion to psychosis and achieved a classification accuracy of 91.7%. The decreased LogEC50 in the CHR-C group was significantly correlated with the increased IL-1ß/IL-10 ratio (Spearman ρ = -0.600, P = .018), but this correlation was nonsignificant in the CHR-NC group.Conclusions: Our findings indicate a significant association between niacin response and psychosis conversion outcomes in individuals with CHR. Compared with peripheral inflammatory cytokines, the niacin response can better predict conversion, although there may be an intersection between the two in biological mechanisms.

A review of different breast reconstruction methods.

Breast reconstruction is necessary for the comprehensive treatment of breast cancer. For successful breast reconstruction, the timing of surgery and the surgical methods used are vital. The methods of breast reconstruction can be divided into implant-based breast reconstruction (IBBR) and autologous breast reconstruction (ABR). With the development of acellular dermal matrix (ADM), IBBR has become more common in clinical practice. However, the choice for the position in which the implant should be placed (prepectoral or subpectoral) and the use of ADM is currently controversial. We summarized the differences in indications, complications, advantages, disadvantages, and prognosis between IBBR and ABR. We also compared the indications and complications of different flaps in ABR and found that the LD (latissimus dorsi) flap is suitable for Asian women who have a low body mass index (BMI) and a low incidence of obesity, while the DIEP (deep inferior epigastric perforator) flap can be used in patients with severe breast ptosis. In conclusion, immediate breast reconstruction with an implant or expander is the primary method, as it causes lesser scarring and requires a shorter time compared to ABR. However, for patients with severe breast ptosis or reluctant to receive an implant, ABR can be performed for a satisfying cosmetic result. Indications and complications of different flaps in ABR are also inconsistent. Surgeons should make surgical plans based on the preferences and conditions of each patient. In the future, breast reconstruction methods need to be further refined, and minimally invasive and personalized approaches need to be implemented to provide more benefits to patients.

Ondansetron: recommended antiemetics for patients with acute pancreatitis? a population-based study.

Objective: Ondansetron administration is a common antemetic of acute pancreatitis therapy in the intensive care unit (ICU), but its actual association with patients' outcomes has not been confirmed. The study is aimed to determine whether the multiple outcomes of ICU patients with acute pancreatitis could benefit from ondansetron. Methods: 1,030 acute pancreatitis patients diagnosed in 2008-2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database as our study cohort. The primary outcome we considered is the 90-day prognosis, and secondary outcomes included in-hospital survival and overall prognosis. Results: In MIMIC-IV, 663 acute pancreatitis patients received ondansetron administration (OND group) during their hospitalization, while 367 patients did not (non-OND group). Patients in the OND group presented better in-hospital, 90-day, and overall survival curves than the non-OND group (log-rank test: in-hospital: p < 0.001, 90-day: p = 0.002, overall: p = 0.009). After including covariates, ondansetron was associated with better survival in patients with multiple outcomes (in-hospital: HR = 0.50, 90-day: HR = 0.63, overall: HR = 0.66), and the optimal dose inflection points were 7.8 mg, 4.9 mg, and 4.6 mg, respectively. The survival benefit of ondansetron was unique and stable in the multivariate analyses after consideration of metoclopramide, diphenhydramine, and prochlorperazine, which may also be used as antiemetics. Conclusion: In ICU acute pancreatitis patients, ondansetron administration was associated with better 90-day outcomes, while results were similar in terms of in-hospital and overall outcomes, and the recommended minimum total dose might be suggested to be 4-8 mg.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Inhomogeneous Microstructure Evolution of 6061 Aluminum Alloyat High Rotating Speed Submerged Friction Stir Processing.

An inhomogeneous microstructure induced by high rotating speed submerged friction stir processing (HRS-SFSP) on 6061 aluminum alloy was researched in detail.The microstructures of the aluminum alloy processing zone were characterized by electron backscattered diffraction (EBSD) and transmission electron microscope (TEM) qualitatively and quantitatively.The results show that the recrystallization proportion in the inhomogeneous structure of the processing zone is 14.3%, 37.8% and 35.9%, respectively. Different degrees of grain deformation can affect the dislocation and lead to the formation of a plastic-elastic interface. At the same time, the second-phase particles in the processing zone were inhomogeneity and relatively, which further promotes the plastic-elastic interface effect. The plastic-elastic interface can significantly improve the strength of aluminum alloy, whileat the same time, rely on recrystallized grains to provide enough plasticity. When the rotation speed was 3600 r/min, the strength and ductility of the aluminum alloy after HRS-SFSP were increased by 48.7% and 10.2% respectively compared with that of BM. In all, the plastic-elastic interface can be formed by using high rotating speed submerged friction stir processing, and the strength-ductility synergy of aluminum alloy can be realized at the plastic-elastic interface.

Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk.

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1ß, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.

Attenuated niacin response is associated with a subtype of first-episode drug-naïve psychosis characterized as serious negative symptoms.

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 EC50 [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 log10 (EC50) 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 log10 (EC50) 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.

Ionic COF Composite Membranes for Selective Perfluoroalkyl Substances Separation.

High-performance membranes are critical to membrane separation technology. In recent years, 2D covalent organic frameworks (2D COFs) have attracted extensive attention in the field of membrane separation due to their high porosity, ordered channels, and fine-tuned pore sizes, which are considered as excellent candidate to solve the trade-off between membrane selectivity and permeability. Herein, two kinds of ionic 2D COFs with different charge properties (termed as iCOFs) are integrated into polyacrylonitrile (PAN) substrates to form two composite membranes (PAN@iCOFs) with excellent selective perfluoroalkyl substances (PFASs) separation performance with high solvent permeability and good mechanical properties. The as-prepared PAN@iCOFs composite membranes can selectively reject more than 99.0% of positively and negatively charged PFASs in wastewater while maintaining good stability and recyclability.

Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study.

Previous studies have revealed that the imbalance between Th1 cytokines and Th2 cytokines plays a role in disturbance of cellular responses in the brain during psychosis. Cross-sectional studies have implied that inflammatory cytokine changes emerge in early psychosis, even at the at-risk stage. This study aimed to test the hypothesis that inflammatory imbalance in clinical high-risk (CHR) individuals is associated with an increased risk of future psychosis. A prospective case-control study was performed to assess the Th1(interleukin (IL)-1ß)/Th2(IL-6) balance in 84 CHR individuals and 65 age- and sex-matched healthy controls (HC). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay at baseline and 1-year after the completion of the clinical assessment. Sixteen (19.0%) CHR participants converted to full psychosis during the 1-year follow-up period. At baseline, serum IL-1ß level was significantly lower in the CHR-converter group - resulting in decreased IL-1ß/IL-6 ratios - compared to those of the CHR-non-converter and HC groups. At the 1-year follow-up, IL-1ß level had decreased, and IL-1ß/IL-6 ratios had decreased in the CHR-non-converter group, such that these were comparable to values in the CHR-converter at this time point. Analysis of the changes in IL-1ß/IL-6 ratio between the baseline and 1-year follow-up measurements identified different trajectories in the CHR-converter and CHR-non-converter groups. Our findings demonstrate that a specific pattern of Th1/Th2 imbalance (decreased IL-1ß/IL-6 ratios with lower serum IL-1ß level) is associated with an increased risk of developing psychosis. Such specific pattern has potential for predicting conversion outcomes and selecting a distinct subgroup of CHR with immune-imbalanced-phenotype, that relevance in precise prevention.

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

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.

Antipsychotic prescription, assumption and conversion to psychosis: resolving missing clinical links to optimize prevention through precision.

The current concept of clinical high-risk(CHR) of psychosis relies heavily on "below-threshold" (i.e. attenuated or limited and intermittent) psychotic positive phenomena as predictors of the risk for future progression to "above-threshold" positive symptoms (aka "transition" or "conversion"). Positive symptoms, even at attenuated levels are often treated with antipsychotics (AP) to achieve clinical stabilization and mitigate the psychopathological severity. The goal of this study is to contextually examine clinicians' decision to prescribe AP, CHR individuals' decision to take AP and psychosis conversion risk in relation to prodromal symptoms profiles. CHR individuals (n = 600) were recruited and followed up for 2 years between 2016 and 2021. CHR individuals were referred to the participating the naturalistic follow-up study, which research procedure was independent of the routine clinical treatment. Clinical factors from the Structured Interview for Prodromal Syndromes (SIPS) and global assessment of function (GAF) were profiled via exploratory factor analysis (EFA), then the extracted factor structure was used to investigate the relationship of prodromal psychopathology with clinicians' decisions to AP-prescription, CHR individuals' decisions to AP-taking and conversion to psychosis. A total of 427(71.2%) CHR individuals were prescribed AP at baseline, 532(88.7%) completed the 2-year follow-up, 377(377/532, 70.9%) were taken AP at least for 2 weeks during the follow-up. EFA identified six factors (Factor-1-Negative symptoms, Factor-2-Global functions, Factor-3-Disorganized communication & behavior, Factor-4-General symptoms, Factor-5-Odd thoughts, and Factor-6-Distorted cognition & perception). Positive symptoms (Factor-5 and 6) and global functions (Factor-2) factors were significant predictors for clinicians' decisions to AP-prescription and CHR individuals' decisions to assume AP, whereas negative symptoms (Factor-1) and global functions (Factor-2) factors predicted conversion. While decisions to AP-prescription, decisions to AP-taking were associated to the same factors (positive symptoms and global functions), only one of those was predictive of conversion, i.e. global functions. The other predictor of conversion, i.e. negative symptoms, did not seem to be contemplated both on the clinician and patients' sides. Overall, the findings indicated that a realignment in the understanding of AP usage is warranted.

Replication of the abnormal niacin response in first episode psychosis measured using laser Doppler flowmeter.

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 log10 (EC50 ) 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 log10 (EC50 ) 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 log10 (EC50 ) 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.

Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis.

Background: Impaired sensitivity of the skin flush response to niacin is one of the most replicated findings in patients with schizophrenia. However, prior studies have usually focused on postonset psychosis, and little is known about the clinical high-risk (CHR) phase of niacin sensitivity in psychosis. Aims: To profile and compare the niacin flush response among CHR individuals (converters and non-converters), patients with first-episode schizophrenia (FES) and healthy controls (HCs). Methods: Sensitivity to four concentrations (0.1-0.0001 M) of aqueous methylnicotinate was tested in 105 CHR individuals, 57 patients with FES and 52 HCs. CHR individuals were further grouped as converters and non-converters according to the 2-year follow-up outcomes. Skin flush response scores were rated on a 4-point scale. Results: Of the 105 CHR individuals, 21 individuals were lost during the study, leaving 84 CHR individuals; 16 (19.0%) converted to full psychosis at 2 years of follow-up. Flush response scores identified in the CHR samples were characterised as modest degree levels, intermediate between those of HC individuals and patients with FES. The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations (0.01 M, 0.1 M) and longer time points (15 min, 20 min); however, these became comparable with the responses in the HC group at the shorter time points and at lower concentrations. The converters exhibited lower mean flush response scores than the non-converters. Conclusions: Attenuated niacin-induced flushing emerged during the early phase of psychosis. New devices should be developed and verified for objective quantification of skin responses in the CHR population.