Impaired motor-to-sensory transformation mediates auditory hallucinations.

Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that "broken" CD plus "noisy" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.

Separable amygdala activation patterns in the evaluations of robots.

Given the increasing presence of robots in everyday environments and the significant challenge posed by social interactions with robots, it is crucial to gain a deeper understanding into the social evaluations of robots. One potentially effective approach to comprehend the fundamental processes underlying controlled and automatic evaluations of robots is to probe brain response to different perception levels of robot-related stimuli. Here, we investigate controlled and automatic evaluations of robots based on brain responses during viewing of suprathreshold (duration: 200 ms) and subthreshold (duration: 17 ms) humanoid robot stimuli. Our behavioral analysis revealed that despite participants' self-reported positive attitudes, they held negative implicit attitudes toward humanoid robots. Neuroimaging analysis indicated that subthreshold presentation of humanoid robot stimuli elicited significant activation in the left amygdala, which was associated with negative implicit attitudes. Conversely, no significant left amygdala activation was observed during suprathreshold presentation. Following successful attenuation of negative attitudes, the left amygdala response to subthreshold presentation of humanoid robot stimuli decreased, and this decrease correlated positively with the reduction in negative attitudes. These findings provide evidence for separable patterns of amygdala activation between controlled and automatic processing of robots, suggesting that controlled evaluations may influence automatic evaluations of robots.

An event-related potential study of prepotent motor activity and response inhibition deficits in schizophrenia.

Response inhibition deficits in schizophrenia (SZ) are accompanied by reduced neural activities using event-related potential (ERP) measurements. However, it remains unclear whether the reduction in inhibition-related ERPs in SZ is contingent upon prepotent motor tendencies. This study aimed to examine the relationship between ERP markers of prepotent motor activity (lateralised readiness potential, LRP) and response inhibition (P3) by collecting behavioural and EEG data from healthy control (HC) subjects and SZ patients during a modified Go/No-Go task. A trial-averaged analysis revealed that SZ patients made more commission errors in No-Go trials compared with HC subjects, although there was no significant difference in the inhibition-related P3 effect (i.e. larger P3 amplitudes in No-Go compared with Go trials) between the two groups. Subsequently, No-Go trials were sorted and median-split into bins of stronger and weaker motor tendencies. Both HC and SZ participants made more commission errors when faced with stronger motor tendencies. The LRP-sorted P3 data indicated that HC subjects exhibited larger P3 effects in response to stronger motor tendencies, whereas this trial-by-trial association between P3 and motor tendencies was absent in SZ patients. Furthermore, SZ patients displayed diminished P3 effects in No-Go trials with stronger motor tendencies but not in trials with weaker motor tendencies, relative to HC subjects. Taken together, these findings suggest that SZ patients are unable to dynamically adjust inhibition-related neural activities in response to changing inhibitory control demands and emphasise the importance of considering prepotent motor activity when investigating the neural mechanisms underlying response inhibition deficits in SZ.

Over 3.8 W, 3.4†µm picosecond mid-infrared parametric conversion based on a simplified one-to-many scheme.

In this paper, we demonstrate a simplified one-to-many scheme for efficient mid-infrared (MIR) parametric conversion. Such a scheme is based on a continuous wave (CW) single longitudinal mode master oscillator power-amplifier (MOPA) fiber system as the signal source and a picosecond pulsed MOPA fiber system, exhibiting multiple longitudinal modes, as the pump source. The signal and pump beams are combined and co-coupled into a piece of 50-mm long 5% MgO-doped PPLN crystal for the parametric conversion. As high as ∼3.82 W average power at a central idler wavelength of ∼3.4 µm is achieved when the launched pump and signal powers are ∼41.73 and ∼11.45 W, respectively. Above some threshold value, the delivered idler power shows a roll-over effect against the signal power and saturation-like effect against the pump power. Consequently, the highest conversion efficiency is observed at such a threshold pump power. To the best of our knowledge, our result represents the highest average power produced from any single-pass parametric conversion source with >3 µm idler wavelength feeding with a CW signal. Moreover, our proposed scheme can simplify the design of parametric conversion system significantly and meanwhile make the system more robust in applications. This is attributed to two main aspects. Firstly, the scheme's one-to-many feature can reduce wavelength sensitivity remarkably in the realization of quasi-phase-matching. Secondly, for moderate power requirement it does not always require a high peak power synchronized pulsed signal source; a CW one can be an alternative, thereby making the system free from complex time synchronization and the related time jitter.

Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Protective factors for children with autism spectrum disorder during COVID-19-related strict lockdowns: a Shanghai autism early developmental cohort study.

BACKGROUND: COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. METHODS: Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects. RESULTS: Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (ß = 0.49, 95% confidence interval (CI) [0.19-0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94-4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (-0.11 [-0.17 to -0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus. CONCLUSIONS: This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

The effects of pre-cue alpha and cueing strategy on age-related deficits in post-cue alpha activity and target processing during visual spatial attention.

Electroencephalography alpha-band (8-13 Hz) activity during visual spatial attention declines in normal aging. We recently reported the impacts of pre-cue baseline alpha and cueing strategy on post-cue anticipatory alpha activity and target processing in visual spatial attention (Wang et al., Cerebral Cortex, 2023). However, whether these factors affected aging effects remains unaddressed. We investigated this issue in two independent experiments (n = 114) with different cueing strategies (instructional vs. probabilistic). When median-splitting young adults (YA) by their pre-cue alpha power, we found that older adults exhibited similar pre-cue and post-cue alpha activity as YA with lower pre-cue alpha, and only YA with higher pre-cue alpha showed significant post-cue alpha activity, suggesting that diminished anticipatory alpha activity was not specific to aging but likely due to a general decrease with baseline alpha. Moreover, we found that the aging effects on cue-related event-related potentials were dependent on cueing strategy but were relatively independent of pre-cue alpha. However, age-related deficits in target-related N1 attentional modulation might depend on both pre-cue alpha and cueing strategy. By considering the impacts of pre-cue alpha and cueing strategy, our findings offer new insights into age-related deficits in anticipatory alpha activity and target processing during visual spatial attention.

The effects of pre-cue posterior alpha on post-cue alpha activity and target processing in visual spatial attention tasks with instructional and probabilistic cues.

The electroencephalography alpha-band (8-13 Hz) activity may represent a crucial neural substrate of visual spatial attention. However, factors likely contributing to alpha activity have not been adequately addressed, which impedes understanding its functional roles. We investigated whether pre-cue alpha power was associated with post-cue alpha activity in 2 independent experiments (n = 30 each) with different cueing strategies (instructional vs. probabilistic) by median-splitting subjects (between-subject) or trials (within-subject) according to pre-cue alpha. In both experiments, only subjects with higher pre-cue alpha showed significant post-cue alpha desynchronization and alpha lateralization, while whether trials had higher or lower pre-cue alpha affected post-cue alpha desynchronization but not alpha lateralization. Furthermore, significant attentional modulation of target processing indexed by N1 component was observed in subjects and trials regardless of higher or lower pre-cue alpha in the instructional cueing experiment. While in the probabilistic cueing experiment, N1 attentional modulation was only observed in higher pre-cue alpha subjects and lower pre-cue alpha trials. In summary, by demonstrating the effects of pre-cue alpha and cueing strategy on post-cue alpha activity and target processing, our results suggest the necessity of considering these 2 contributing factors when investigating the functional roles of alpha activity in visual spatial attention.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Does Electroencephalography Seizure Duration Account for an Adequate Treatment of Magnetic Seizure Therapy for Schizophrenia?

OBJECTIVES: A seizure lasting >15 s has been considered to indicate treatment for magnetic seizure therapy (MST), a modification of electroconvulsive therapy (ECT), without much validation. This study aimed to investigate whether this seizure duration was suitable for the treatment of schizophrenia. METHODS: Altogether, 34 and 33 in-patients with schizophrenia received 10 sessions of MST and ECT, respectively. Clinical symptoms were assessed using the Positive and Negative Symptom Scale at baseline and at the 4-week follow-up. Electroencephalogram (EEG) was monitored during each MST or ECT treatment using bifrontal electrodes. RESULTS: The proportion of participants who achieved the 15-second threshold was only 28.6% in the MST group, with a significant difference between responders and nonresponders. For patients receiving MST, the average EEG seizure duration correlated with the percentage of Positive and Negative Symptom Scale reduction (t(32) = 2.51, P = 0.017, uncorrected; t(32) = 2.00, P = 0.055, corrected with clinical characteristics). The average EEG seizure duration predicted the clinical response at a trend level (Z = 1.76, P = 0.078) with an optimal cutoff of 11.3 seconds. All patients in the ECT group achieved the 15-second threshold. However, their average EEG seizure duration was uncorrelated with clinical improvement. CONCLUSIONS: The duration of EEG seizures may be associated with the antipsychotic effects of MST. This association may have been influenced by various clinical and technical factors. More research is needed to define the specific criteria for adequate MST in schizophrenia in order to achieve personalized dosing.

Trends in the prevalence of cognitive impairment at old age in China, 2002-2018.

INTRODUCTION: China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018. METHODS: Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old. RESULTS: The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age-standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence. DISCUSSION: The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow-up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend. HIGHLIGHTS: Generalized estimating equations (GEE) were used to assess trends of changes in cognitive impairment (CI). CI prevalence in China increased from 2002 to 2008 and then decreased until 2018. Females and those ≥ 80 years old had greater CI prevalence. Stroke, diabetes, and cigarette smoking were risk factors for CI.

Differential responses of soil phosphorus fractions to varied nitrogen compound additions in a meadow steppe.

Nitrogen (N) addition can greatly influence soil inorganic phosphorus (Pi) and organic phosphorus (Po) transformations. However, whether and how the N compound forms may differentially affect the soil P fractions remain unclear. Here, we investigated the responses of soil Pi (labile Pi, moderately-occluded Pi, and recalcitrant Pi) and Po fractions (labile Po and stable Po) to varying addition rates of three N compounds ((NH4)2SO4, NH4NO3, and urea) in a meadow steppe in northern China. Our studies revealed that with increasing N addition rate, soil labile and moderately-occluded Pi increased, accompanied by decreases in soil recalcitrant Pi. This shift was attributed to N-induced soil acidification, which accelerated the conversion of recalcitrant Pi into labile and moderately-occluded Pi. Soil labile Po decreased with increasing rate of N addition, whilst soil stable Po was not affected. Regardless of the compound forms, N addition increased soil Olsen-P, suggesting a potential alleviation of P limitation in this grassland ecosystem. The effect of N addition on soil labile Pi was significantly greater with addition of urea than with addition of either (NH4)2SO4 or NH4NO3, indicating that urea was more efficient in enhancing soil P availability. Addition of (NH4)2SO4 imposed a more pronounced positive effect on soil moderately-occluded Pi than the addition of either NH4NO3 or urea, mainly due to the greater mobilization of recalcitrant Pi as a result of higher soil acidification strength of (NH4)2SO4. These findings underscore the importance of considering the distinct effects of different N compounds when studying grassland soil P dynamics and availability in response to N addition.

Diverse intratumoral heterogeneity and immune microenvironment of two HPV-related cervical cancer types revealed by single-cell RNA sequencing.

Cervical squamous cell carcinoma (SCC) and adenocarcinoma (AD) are the main histological types of human papillomavirus-related cervical cancer. However, there are few reports on cell type-specific molecular differences between SCC and AD. Here, we used unbiased droplet-based single-cell RNA sequencing to elucidate the cellular differences between SCC and AD in tumor heterogeneity, and tumor microenvironment (TME). A total of 61 723 cells from three SCC and three AD patients, were collected and divided into nine cell types. Epithelial cells exhibited high intra- and interpatient heterogeneity and functional diversity. Signaling pathways, such as epithelial-to-mesenchymal-transition (EMT), hypoxia and inflammatory response were upregulated in SCC, while cell cycle-related signaling pathways were highly enriched in AD. SCC was associated with high infiltration of cytotoxicity CD8 T, effector memory CD8 T, proliferative natural killer (NK), and CD160+ NK cells as well as tumor-associated macrophages (TAMs) with high major histocompatibility complex-II genes. AD exhibited a high proportion of naive CD8 T, naive CD4 T, Treg CD4, central memory CD8, and TAMs with immunomodulatory functions. Additionally, we also observed that the majority of cancer-associated fibroblasts (CAFs) were from AD, and participated in inflammation regulation, while SCC-derived CAFs exhibited similar functions to tumor cells, such as EMT and hypoxia. This study revealed the widespread reprogramming of multiple cell populations in SCC and AD, dissected the cellular heterogeneity and characteristics in TME, and proposed potential therapeutic strategies for CC, such as targeted therapy and immunotherapy.

Drop Impact on Submillimeter-Structured Surfaces with Different Wetting Behaviors.

Droplet impact behaviors are crucial in controlling infectious diseases, inkjet printing, and anti-icing applications. The wettability and microstructure of the material surface are critical factors in this regard. Compared to microstructures, submillimeter structures are more damage-resistant, thereby ensuring droplet impact behaviors' stability. Herein, submillimeter-structured PDMS surfaces with varying wetting properties were prepared to investigate droplet impact behaviors. Experimental results indicate that submillimeter-structured surfaces are more prone to droplet splashing than flat surfaces, which can be suppressed by increasing surface hydrophilicity. An increase in the submillimeter pillar height and a decrease in spacing result in an increased critical Weber number. Additionally, the capillary forces of the superhydrophilic surface lead to droplet impact, accompanied by deposition. This study supports the long-term stable use of the droplet impact effect to achieve fluid separation.

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.

Identifying the pathophysiological traits of obstructive sleep apnea during dexmedetomidine sedation.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared. Bivariate and multivariate linear regression analyses were used to estimate the relationship between pathophysiological traits and OSA severity for both sleep states. Adult patients with OSA had a significantly higher pharyngeal collapsibility (Vpassive : 44.9 [15.7 to 53.8] vs. 53.3 [34.2 to 66.3] %eupnea , p < 0.001), arousal threshold (178.5 [132.5 to 234.6] vs. 140.5 [123.2 to 192.3] %eupnea , p < 0.001), and loop gain (LG1: 0.74 ± 0.25 vs. 0.60 ± 0.17, p < 0.001; LGn: 0.52 ± 0.12 vs. 0.44 ± 0.08, p < 0.001) during DEX-induced sleep compared with natural sleep. There was no significant difference in dilator muscle function or PSG respiratory parameters between natural versus DEX-induced sleep states. Bivariate regression analysis showed varying degrees of correlation between OSA traits and severity. Multiple regression analysis indicated that collapsibility was the strongest predictor of the apnea-hypopnea index for both sleep states. Dexmedetomidine sedation in patients with OSA increased the pharyngeal collapsibility without impairing dilator muscle function, while elevating arousal threshold and increasing loop gain.

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.

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.

Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis.

BACKGROUND: Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy. AIMS: To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia. METHOD: We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). RESULTS: We included 59 trials (15,781 participants; mean age, 76.6 years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] -0.20, 95% credible interval [CrI] -0.40 to -0.10) and galantamine (-0.20, -0.39 to -0.02) were more effective than placebo in short-term treatment (median duration: 12 weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38-2.94) and rivastigmine (1.87, 1.24-2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA. CONCLUSIONS: Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk-benefit profile of drugs.