Exacerbation Of Psychosis Research Articles

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials

BackgroundCurrently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M1 /M4 preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms. MethodsData were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample N = 640). PANSS criteria proposed in the literature identified a subset of study participants (n = 64) with prominent NS. ResultsKarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (p < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility. ConclusionsParticipants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.

Use of video-recordings of site-based interviews for quality assurance in a study of subjects with schizophrenia and persistent negative symptoms

Site-independent ratings derived from audio-digital recordings of site-based interviews are often used for quality assurance monitoring to affirm ratings reliability in CNS clinical trials. The present study of subjects with schizophrenia and persistent negative symptoms used video instead of audio recordings of site-based interviews and thereby facilitated visual observation of the subject by the remote rater. “Paired” site-independent scores of the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS) were obtained from video-recordings of site-based interviews.The intraclass correlation between site-based and paired site-independent ratings was r = 0.839 for the total PANSS scores (n = 1006) and r = 0.871 for the total BNSS scores (n = 892); <5 % of paired scores deviated outside the acceptable confidence intervals. Ratings “outliers” were identified and remediated.We examined the pattern of paired scoring deviations for the BNSS, total PANSS, PANSS symptom subscales, and the Marder negative symptom factor. Each metric revealed a bidirectional pattern of scoring deviations such that mean site-based ratings were higher than site-independent ratings when symptom severity was high but lower than site-independent ratings when symptom severity was low.The pattern of bidirectional paired scoring deviations observed in this analysis has previously been noted in paired ratings analyses of subjects experiencing an acute exacerbation of psychosis in schizophrenia and major depressive disorder as well. The bidirectional pattern may reflect inherent differences between live ratings and remotely scored recorded ratings.This analysis affirms the utility of video-recordings of site-based ratings for surveillance in trials with subjects with schizophrenia and persistent negative symptoms.

Differential effects of cannabis constituents on schizophrenia-related psychosis: a rationale for incorporating cannabidiol into a schizophrenia therapeutic regimen.

Schizophrenia is a serious mental health disorder that confers one of the highest mortality rates of all psychiatric illnesses. Although the disorder's psychotic symptoms are treatable with conventional antipsychotics, they remain incurable. Moreover, medication adherence is poor, and individuals with schizophrenia choose to self-medicate with illicit substances, including cannabis. It is well-established that the delta-9-tetrahydrocannabinol (delta-9-THC) component of cannabis elicits psychotomimetic effects at high doses; worsens schizophrenia-related psychosis; commonly develops into cannabis use disorder in individuals with schizophrenia; and increases the risk of earlier-onset schizophrenia symptoms in those harboring genetic susceptibility. However, individuals with schizophrenia commonly use cannabis and cannabis derivatives such as cannabidiol (CBD). These products seem to alleviate psychotic symptoms and relieve adverse side effects of antipsychotic medications. Therefore, one notion that has gained traction is the potential utility of cannabis-derived cannabidiol (CBD) as adjunct treatment to reduce schizophrenia-associated psychosis and other symptoms. Currently, preclinical and clinical data remain inconclusive. The present review distinguishes the mechanisms underlying schizophrenia-associated vs. cannabis-induced psychosis; reviews the evidence for delta-9-THC-mediated exacerbation vs. CBD-mediated amelioration of schizophrenia-associated psychosis; and describes potential approaches for incorporating CBD into schizophrenia therapeutic regimen in a safe and efficacious manner.

Adverse Events Reporting in Digital Interventions Evaluations for Psychosis: A Systematic Literature Search and Individual Level Content Analysis of Adverse Event Reports.

Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs. A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports. We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants. The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided.

Targeted Treatment of Schizophrenia Symptoms as They Manifest, or Continuous Treatment to Reduce the Risk of Psychosis Recurrence.

Current pharmacological treatment of schizophrenia employs drugs that interfere with dopamine neurotransmission, aiming to suppress acute exacerbation of psychosis and maintenance treatment to reduce the risk of psychosis recurrence. According to this treatment scheme, available psychotropic drugs intended to treat negative symptoms, cognitive impairment, or anxiety are administered as add-ons to treatment with antipsychotics. However, an alternative treatment scheme proposes a targeted or intermittent treatment approach, by which antipsychotic drugs are administered upon psychosis exacerbation and discontinued upon remission or stabilization, while negative symptoms, cognitive impairment, or anxiety are treated with specific psychotropics as monotherapy. Along these lines, antipsychotics are renewed only in the event of recurrence of psychotic symptoms. This 50-year-old debate between targeted and continuous treatment schemes arises from disagreements about interpreting scientific evidence and discordant views regarding benefit/risk assessment. Among the debate's questions are: (1) what is the percentage of individuals who can maintain stability without antipsychotic maintenance treatment, and what is the percentage of those who exacerbate despite antipsychotic treatment? (2) how to interpret results of placebo-controlled 9- to 18-month-long maintenance trials in a life-long chronic disorder, and how to interpret results of the targeted trials, some of which are open label or not randomized; (3) how to weigh the decreased risk for psychotic recurrence vs the almost certainty of adverse effects on patient's quality of life. Patients' profiles, preferences, and circumstances of the care provision should be considered as the targeted vs continuous treatment options are considered.

Systematic review of the association between adverse life events and the onset and relapse of postpartum psychosis.

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260592], identifier [CRD42021260592].

Lumateperone in Pooled Late-Phase Schizophrenia Trials: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed

AbstractBackgroundLumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder as monotherapy and as adjunctive therapy with lithium or valproate. This post hoc analysis investigated the efficacy and tolerability of lumateperone in patients with schizophrenia via number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).MethodsData were pooled from three late-phase 4–6 week placebo-controlled studies of lumateperone 42 mg/day in adults with schizophrenia and an acute exacerbation of psychosis (Study 005 [NCT01499563], Study 301 [NCT02282761], Study 302 [NCT02469155]). NNT and NNH were calculated vs placebo for several different Positive and Negative Syndrome Scale [PANSS] Total score response cutoffs (percent reduction from baseline) and for adverse events (AEs), respectively.ResultsIn the two informative studies (placebo, n=221; lumateperone, n=224), the NNT vs placebo for lumateperone was statistically significant for PANSS Total score reductions from baseline to 4 weeks/endpoint of ≥20% (NNT=9, 95% confidence interval [CI] 5–36) and ≥30% (NNT=8; 95%CI 5–21). In all studies pooled (placebo, n=412; lumateperone, n=406), study discontinuations due to AEs were uncommon and the NNH (389) was not statistically significant from placebo. The only AE with NNH vs placebo &lt;10 was somnolence/sedation (NNH=8; 95%CI 6–12). With lumateperone treatment, weight gain ≥7% from baseline was similar to placebo (NNH=112) and fewer patients experienced akathisia than placebo. Lumateperone LHH ratios were &gt;&gt;1 for all AEs (range 13.6–48.6) except somnolence/sedation (LHH~1).ConclusionLumateperone’s benefit-risk profile was favorable in late-phase schizophrenia trials.FundingIntra-Cellular Therapies, Inc.

Sex-related differences in medical cannabis use: A nation-wide database study

IntroductionCannabis use is associated with mental illness among men and women, especially induction or exacerbation of psychosis, anxiety, and depression. Although safety and efficacy of cannabis in most medical conditions have not been established, use of medical cannabis is growing exponentially. In particular, albeit sex-related differences in the activity of the endocannabinoid system in animals and humans, differential effects of cannabis on men and women have rarely been sought.ObjectivesTo characterize patterns of use and adverse effects experienced by men and women using medical cannabis.MethodsData from the Israeli national database of patients licensed to use medical cannabis in Israel from January 2014 to December 2021 was analyzed. The database includes indications for cannabis use, monthly cannabis quantities, Tetrahydrocannabinol (THC) and Cannabidiol (CBD) concentrations, and reports of adverse effects. Comparative statistics were used to evaluate the sex related differences.Results161,644 persons (62% men) were issued a license to use medical cannabis during the study period. Men are significantly younger than women (50.5±19.1 vs. 56.5±18.4). The leading indications among both men and women are chronic pain (58% of men, 57% of women), symptoms related to oncological disease and chemotherapy treatment (21% of men, 24% of women) and post-traumatic stress disorder (9% of men, 6% of women). Men consume significantly higher monthly quantities at the beginning of treatment compared to women (31.6 gram vs. 29.3 gram) with a higher THC concentration (13.9% vs. 11.6%) and lower CBD concentration (5.3% vs. 6.7%). Over two years of use, there is an increase among both men and women in the amount and THC concentration, and a decrease in the CBD concentration. The differences between men and women remain significant throughout the whole period. Data on adverse effects are available for 28,629 men and 17,204 women (28.6% of men, 28.0% of women). Women report significantly more physical adverse effects (RR 1.48 [95%CI 1.39-1.57]), anxiety (RR 1.45 [95%CI 1.35-1.56]), depression (RR 1.36 [95%CI 0.95-1.96]) and derealization (RR 3.44 [95%CI 2.42-4.89]).ConclusionsAlthough the prevalence of medical conditions for which medical cannabis is indicated are similar for both genders, approximately 60% more men consume medical cannabis. While consuming lower cannabis amount and THC concentration, women report more physical and psychiatric adverse effects than men. Understanding the differences in usage patterns and adverse effects between men and women will enable more accurate policy determinations and more effective and safer treatment strategies.Disclosure of InterestNone Declared

Exacerbation of Pica as a Precursor of Psychosis

Abstract Pica is a sustained, compulsive eating behavior of nonedible substances. Pica has been described as sequelae of psychosis due to its state of disorganization; however, temporal and causal relationship between the two has not been reported in the context of exacerbation of pica before psychosis. Various causes of pica have been identified including malnutrition, iron-deficiency anemia, zinc deficiency, intellectual disability, and obsessive and impulse control disorders. Here, we describe a case of worsening pica which preceded exacerbation of psychosis in an 18-year-old female which was managed with antipsychotics along with complete remission of psychosis and improvement in the severity of pica. The present case highlights the association between psychosis and pica. There has been a rising voice in academia to reclassify pica alongside obsessive–compulsive disorder (OCD) with no absolute consensus. In conclusion, our findings suggest that the exacerbation of pica preceded psychosis and can be construed as an indicator for an upcoming psychotic episode or as a prodromal aspect of psychosis and may be useful for early identification and initiation of treatment in cases of relapsing psychosis.

Clinical Practice Guidelines for the Use of Electroconvulsive Therapy.

Clinical Practice Guidelines for the Use of Electroconvulsive Therapy.

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation.

Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology.

Cannabidiol, but Not Δ9-Tetrahydrocannabinol, Has Strain- and Genotype-Specific Effects in Models of Psychosis.

Introduction: Cannabis use has been associated with an increased incidence of psychiatric disorders, yet the underlying neurobiological processes mediating these associations are poorly understood. Whereas exposure to Δ9-tetrahydrocannabinol (THC) has been associated with the development or exacerbation of psychosis, treatment with cannabidiol (CBD) has been associated with amelioration of psychosis. In this study, we demonstrate a complex effect of CBD in mouse models of psychosis, based on factors, including dose, strain, and genotype. Methods: Adult GluN1 knockdown (GluN1KD) and dopamine transporter knockout (DATKO) mice (almost equally balanced for male/female) were acutely treated with vehicle, THC (4 mg/kg), CBD (60, 120 mg/kg), or THC:CBD (1:15, 4:60 mg/kg) and tested in behavioral assays. Results: GluN1KD and DATKO mice displayed hyperactivity, impaired habituation, and sensorimotor gating, along with increased stereotypy and vertical activity. THC, alone and in combination with CBD, produced a robust "dampening" effect on the exploratory behavior regardless of strain or genotype. CBD exhibited a more complex profile. At 60 mg/kg, CBD had minimal effects on horizontal activity, but the effects varied in terms of directionality (increase vs. decrease) in other parameters; effects on stereotypic behaviors differ by genotype, while effects on vertical exploration differ by strain×genotype. CBD at 120 mg/kg had a "dampening" effect on exploration overall, except in GluN1KD mice, where no effect was observed. In terms of sensorimotor gating, both THC and CBD had minimal effects, except for 120 mg/kg CBD, which exacerbated the acoustic startle response. Conclusions: Here, we present a study that highlights the complex mechanism of phytocannabinoids, particularly CBD, in models of psychosis-like behavior. These data require careful interpretation, as agonism of the cannabinoid receptor 1 (CB1) resulting in a decrease in locomotion can be misinterpreted as "antipsychotic-like" activity in murine behavioral outputs of psychosis. Importantly, the THC-mediated decrease in hyperexploratory behavior observed in our models (alone or in combination) was not specific to the genetic mutants, but rather was observed regardless of strain or genotype. Furthermore, CBD treatment, when comparing mutants with their wild-type littermate controls, showed little to no "antipsychotic-like" activity in our models. Therefore, it is not only important to consider dose when designing/interpreting therapeutically driven phytocannabinoid studies, but also effects of strain or genetic vulnerability respective to the general population.

COVID-Associated Exacerbation of Acute Psychosis in a Patient With Schizoaffective Disorder.

COVID-Associated Exacerbation of Acute Psychosis in a Patient With Schizoaffective Disorder.

Metabolomics and Cytokine Analysis for Identification of Schizophrenia with Auditory Hallucination.

To investigate the metabolic profile and biomarkers of schizophrenia with auditory hallucinations (AHs). A total of 18 schizophrenic patients with the symptom of pure AHs (pAHs), 28 without AH (nAHs) and 43 age-matched healthy persons (Con) were enrolled in this study. Participants in pAHs and nAHs groups had relapsed into exacerbations of psychosis after self-discontinuing antipsychotics for at least one month; blood samples were drawn prior to restarting anti-psychotic treatment. Participants with history of recreational substance use were excluded. Positive and Negative Syndrome Scale (PANSS) and Auditory Hallucinations Rating Scale (AHRS) were used to assess the clinical mental state of all samples. Enzyme-linked immunosorbent assay (ELISA) was used to estimate the level of cytokines, and metabolomics analysis to identify potential biomarkers and pathways in the three groups. Graphpad 8.0 software was used to calculate the area under the receiver operating characteristic (ROC) curve. The relationship between metabolites and cytokines were determined using correlation analysis. Questionnaire scores showed significant differences in the positive symptom scale and PANSS total between nAHs and pAHs groups. Four cytokines (BDNF, IL-2, NGF-β and TNF-α) differed significantly among the three groups. Six molecules in the nAHs group (phenylalanine, hippurate, serine, glutamate, valine and cystine) and four in the pAHs group (phenylalanine, serine, glutamate and cystine) were identified as potential biomarkers. In addition, phenylalanine was shown as a potential independent diagnostic biomarker for pAHs. Correlation analysis revealed that cystine and serine were significantly negatively correlated with IL-2 in the pAHs group. This study revealed the metabolic profile of patients with schizophrenia with AHs and provided new information to support the diagnosis. The identification of unique biomarkers would contribute to objective and reliable diagnoses of patients with schizophrenia with AH.

A qualitative analysis of literature reporting and linking psychosis to COVID-19 infection. Findings from a postgraduate journal club.

Acute exacerbations of psychosis have been reported with COVID-19 infection and medications used for its treatment. Terms “psychosis”, “psychotic”, “COVID-19″ and “coronavirus” were searched on “PubMed” and “GOOGLE SCHOLAR”, yielding 84 articles. 14 case reports were selected based on pre-defined criteria and analyzed. Among selected articles,10 attributed psychosis to COVID-19 infection. In 3 articles, psychosis was diagnosed despite concurrent delirium. In 8 and 3 articles respectively, a clear temporal demarcation of psychosis and COVID-19 infection and steroid use was not described. Psychosis can occur secondary to GMC, or exposure to medication. Due process should be followed to ascertain the same.IntroductionNeurotropic coronavirus infection is associated with numerous neurological and neuropsychiatric manifestations. Such presentations before, during and after the infection have been reported. Among these presentations, acute exacerbations of psychosis have been reportedly linked with COVID-19 infection and medications used for its treatment.MethodologySearch engines “PubMed” AND “GOOGLE SCHOLAR” were searched using specific search terms during June 2021. Out of 84 articles that came up, we selected 14 articles based on pre-determined inclusion and exclusion criteria. Selected articles were analysed and discussed in the departmental journal club.ResultsIn 10 articles, diagnosis of psychosis was attributed to COVID-19 infection. In 3 of those articles, despite reporting concurrent delirium like presentation, diagnosis was still reported as psychosis. In 8 articles, the temporal correlation between onset of psychosis, onset of COVID-19 was not clearly demarcated. In 3 articles, clear demarcation between psychosis associated with steroid use and with a general medical condition (COVID-19) was not clearly presented. Only 2 articles did mention using a structured diagnostic system. In patients (3/17) with prior history of psychiatric illness, diagnosis was reported as relapse of psychosis (2/17), without specifying the criteria used for diagnosing a relapse.ConclusionAcute exacerbation of psychosis can occur secondary to a general medical condition (GMC), or after exposure to a medication. However, due process should be followed to ascertain that the psychosis is indeed secondary to a GMC, or a medication, and not a de-novo presentation, or delirium.

"The World Will End and No One Can Save Us": A Case Series of COVID-Related Exacerbation of Psychosis During the COVID-19 Pandemic.

Anxiety and fear have been elevated during the COVID-19 pandemic, requiring psychiatric intervention in some patients. Here, read about 3 cases of exacerbation of psychiatric illness leading to psychiatric hospitalization that were related to COVID-19.

SELF-DESTRUCTIVE BEHAVIOR IN PATIENTS WITH SCHIZOPHRENIA SPECTRUM DISORDERS. FEATURES OF PATHOGENESIS AND PATHODYNAMICS.

The aim: To prove the heterogeneity of pathogenetic mechanisms and pathodynamics of self-destructive behaviour (SdB) in patients with schizophrenia spectrum disorders (SSD). Materials and methods: We examined 112 patients with different kinds of SSD: 55 men (49.1%) and 57 women (50.9%), 34.9±8 years old. In 44.6% of patients the features of SdB were present during more than half of disease time (Gr1) - before and after self-injury or suicidal attempt (SI\SA) as well as in acute psychosis exacerbation or in remission. They committed SI\SA mainly in a psychotraumatic situations and due to permanent feelings with a self-destructive content. In 55.4% of patients (Gr2) acute manifestations of SdB with realization of impulsive SI\SA were caused only as secondary symptoms of the severe exacerbation of psychosis. Self-destructive or suicidal ideas disappeared in Gr2 patients after the reduction of acute psychotic symptoms. Results: Psychometric testing by the PANSS confirmed the comparability of these groups. линеpatients' reaction on a psychological problems, especially family conflicts, the desire to reduce the high level of subjective anxiety or to draw attention to themselves. In 92% of these patients at the moment of examination manifestations of SDB and the same self-destructive motives persisted. While patients of Gr2 committed impulsive SI\SA only by the influence of command pseudohallucinations or delusional ideas at the acute psychosis. At the time of the study (in state without acute psychotic symptoms or in remission) all patients of Gr2 showed no SDB signs. The data according to the Big Five Personality Test fixed substantial distinctions in personal characteristics of patients in Gr1 and Gr2 as well. Conclusions: Our study proved the scientific hypothesis that the pathogenesis and dynamics of SdB in patients with SSD (who committed SI\SA) have essential differences. The research results allowed to describe two types of personal portrait of patients with SSD and SdB who had realized SI\SA. This crucial pathogenetic variances are important to design of the therapy strategies of those patients.

A Case Report on Treatment-Resistant Acute Exacerbation of Psychosis in Pregnancy

Background: This case is interesting because her psychosis was exacerbated at the same time as her new pregnancy onset, and the patient had multiple gestational records. Furthermore, her psychosis was treatment-resistant to Aripiprazole. Case Report: A 36 year-old woman with a gestational age of 27 weeks presented to the Behavioral Health Unit due to acute psychosis of carrying the “Devil’s child.” Conclusion: We hope this case report can serve as a basis for establishing management guidelines for patients with peripartum acute psychosis.

Short-term air pollution exposure and exacerbation of psychosis: A case-crossover study in the capital city of South Korea

There is a growing concern that air pollution exacerbates mental disorders. However, studies assessing the relationship between short-term exposure to ambient air pollution and acute exacerbation of psychotic symptoms in psychiatric disorders are limited. This study aims to examine the association between short-term air pollution exposure and acute exacerbation of psychosis in diverse psychiatric disorders. We analyzed 15,917 patients with psychosis (schizophrenia and related disorders and mood disorders with psychotic features) who visited Emergency Departments (EDs) in Seoul, South Korea, between 2008 and 2016. We estimated short-term exposures to particles <2.5 μm (PM2.5), particles <10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). We employed a conditional logistic regression with a time-stratified case-crossover design to compare the levels of ambient air pollution on ED visit days with those on control days. Results show that the risk of ED visits for psychosis was significantly associated with interquartile range increases in PM2.5 (Odds Ratio [OR] = 1.028; 95% Confidence Interval [CI]: 1.006, 1.049), PM10 (OR = 1.022; 95% CI: 1.003, 1.040), NO2 (OR = 1.037; 95% CI: 1.007, 1.068), and SO2 (OR = 1.030; 95% CI: 1.003, 1.058) in the best-fitting lags. Exposure to the highest quartile of air pollutants generally showed a higher risk for psychosis. The associations were higher among male patients, those with schizophrenia and related disorders, and in the cold season. This study provides new evidence that short-term exposure to elevated levels of air pollutants may increase the risk of acute exacerbation of psychosis. These findings could contribute to the development of policies for reducing air pollution levels and the presentation of psychoses. Further studies are warranted to elucidate our findings and explore the underlying mechanisms.

Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial

Blinded, site-independent (remote) ratings from audio-digital recordings of site-based Positive and Negative Syndrome Scale (PANSS) interviews were obtained in a 5-week, randomized, double-blinded study assessing the safety, tolerability, and efficacy of KarXT (a fixed combination of xanomeline and trospium chloride) in hospitalized adults with schizophrenia experiencing an acute exacerbation of psychosis (EMERGENT-1; ClinicalTrials.gov identifier: NCT3697252). The blinded site-independent raters had no knowledge of site location, study visit, drug vs. placebo assignment, or any treatment emergent adverse events (TEAEs). Concordance analyses of 561 paired site-based and site-independent PANSS ratings across all visits revealed a high correlation (ICC = 0.775). Paired scoring differences were positively correlated with the PANSS total score (Spearman's rho = 0.37, p < 0.0001). Paired PANSS scores were available from 148 subjects at both the baseline and end of study visits (KarXT = 72, Placebo = 76). Site-based PANSS total scores (primary aim) revealed a significantly greater improvement from baseline in the KarXT group compared to the placebo group (p < 0.0001). The blinded site-independent PANSS total scores derived from listening to and scoring the recorded site-based PANSS interviews replicated this finding (p < 0.001) and yielded an overall predictive value of 85.1% for matching the site-based response/non-response outcomes. TEAE's have the potential to “unblind” site-based ratings. In this study, the site-independent raters were blinded to TEAEs, affirmed the site-based PANSS ratings, and mitigated concerns about possible functional unblinding of site-based raters. This method of blinded assessment via audio-digital recordings may have utility for other studies concerned with ratings precision and/or functional unblinding.