Acidente crotálico seguido por primeiro episódio psicótico: um folclore clínico / Rattlesnake bite accident followed by first psychotic episode: a clinical folklore / Accidente crotálico seguido de primer episodio psicótico: un folclore clínico

Introdução: Acidentes ofídicos são doenças negligenciadas e constituem uma parcela importante da morbidade de pessoas em idade produtiva que vivem em zonas rurais. A maior parte dos seus efeitos a curto prazo é amplamente conhecida, especialmente aqueles de natureza clínica; no entanto, ainda se observa lacuna importante do conhecimento das consequências a longo prazo de tais agravos, notadamente as de ordem psíquica. Este artigo relata um caso de adoecimento mental subsequente a um acidente crotálico e gera reflexões de âmbito cultural e fisiopatológico a respeito das sequelas de tais eventos. Apresentação do caso: Trata-se de adolescente residente no interior baiano que foi vítima de mordedura por cascavel e teve necessidade de hospitalização em unidade de terapia intensiva. Observou-se que, mesmo após melhora clínica, iniciou com sintomas psicóticos prodrômicos e progrediu para piora mental grave, que culminou em internação psiquiátrica e diagnóstico de esquizofrenia no decorrer dos meses seguintes. Conclusões: Nota-se, neste caso, correlação direta entre esses dois eventos; mas, em razão da escassez de trabalhos científicos que abordem tais questões, depreende-se que é preciso investigar e estudar com maior profundidade possíveis associações entre acidentes crotálicos e psicoses.

Introduction: Snakebites are neglected diseases and constitute an important part of the morbidity of working-age people who live in rural areas. Most of their short-term effects are widely known, especially those of a clinical nature; however, there is still an important gap in the knowledge of the long-term consequences of such injuries, notably those of a psychotic nature. This article aims to report a case of mental illness subsequent to a rattlesnake bite accident and generate cultural and pathophysiological reflections regarding the consequences of such events. Case presentation: An adolescent residing in the interior of the state of Bahia was bitten by a rattlesnake and required hospitalization in an intensive care unit. It was observed that even after clinical improvement, the case started with prodromal psychotic symptoms and progressed to severe mental deterioration that culminated in psychiatric hospitalization and diagnosis of schizophrenia over the following months. Conclusions: In this case, there was a direct correlation between these two events, but because of the scarcity of scientific works that address such issues, it is necessary to investigate and study in greater depth possible associations between snakebite accidents and psychoses.

Introducción: Las mordeduras de serpientes son enfermedades desatendidas y constituyen una parte importante de la morbilidad de las personas en edad laboral que viven en zonas rurales. La mayoría de sus efectos a corto plazo son ampliamente conocidos, especialmente los de carácter clínico; sin embargo, todavía existe un importante vacío en el conocimiento de las consecuencias a largo plazo de este tipo de lesiones, en particular las de carácter psíquico. Este artículo tiene como objetivo informar un caso de enfermedad mental posterior a un accidente crotálico y generar reflexiones culturales y fisiopatológicas sobre las consecuencias de tales eventos. Presentación del caso: Se trata de un adolescente residente en el interior de Bahía que fue mordido por una serpiente cascabel y requirió hospitalización en unidad de cuidados intensivos. Se observó que, aún después de la mejoría clínica, comenzó con síntomas psicóticos prodrómicos y progresó a un deterioro mental severo que culminó con hospitalización psiquiátrica y diagnóstico de esquizofrenia en los meses siguientes. Conclusiones: En este caso, existe una correlación directa entre estos dos eventos pero, debido a la escasez de trabajos científicos que aborden tales cuestiones, parece necesario investigar y estudiar con mayor profundidad posibles asociaciones entre accidentes crotálicos y psicosis.

How "global" is research in early intervention for psychosis? A bibliometric analysis.

INTRODUCTION: Unlike high-income countries (HICs), there are few early intervention services for psychosis in low-and middle-income countries (LAMICs). In HICs, research spurred the growth of such services. Little is known about the state of EIP research in LAMICs, which we address by examining their research output and collaborations vis-à-vis that of HICs. METHODS: We conducted a search in Scopus database for early psychosis publications in scientific journals since 1980. Data from each record, including title, author affiliation, and date, were downloaded. For HIC-LAMIC collaborations, data on first, corresponding and last authors' affiliations, and funding were manually extracted. Descriptive statistics and social network analysis were conducted. RESULTS: Globally, early psychosis publications increased from 24 in 1980 to 1297 in 2022. Of 16,942 included publications, 16.1 % had LAMIC authors. 71.3 % involved authors from a single country (regardless of income level). 21.9 % were collaborations between HICs, 6.6 % between HICs and LAMICs, and 0.2 % among LAMICs. For research conducted in LAMICs and involving HIC-LAMIC collaborations, the first, last, and corresponding authors were LAMIC-based in 71.8 %, 60.7 %, and 63.0 %, respectively. These positions were dominated (80 %) by authors from four LAMICs. 29.4 % of the HIC-LAMIC subset was funded solely by LAMIC funders, predominantly two LAMICs. CONCLUSIONS: LAMICs are starkly underrepresented in the otherwise flourishing body of early psychosis research. They have far fewer collaborations and less funding than HICs. Closing these gaps in LAMICs where most of the world's youth live is imperative to generate the local knowledge needed to strengthen early psychosis services that are known to improve outcomes.

Clozapine use in the first two years after first-episode psychosis in a real-world clinical sample.

BACKGROUND: Approximately 20-30% of patients with schizophrenia fail to respond to antipsychotic treatment and are considered treatment resistant (TR). Although clozapine is the treatment of choice in these patients, in real-world clinical settings, clinicians often delay clozapine initiation, especially in first-episode psychosis (FEP). AIM: The main aim of this study was to describe prescription patterns for clozapine in a sample of patients diagnosed with FEP and receiving specialized treatment at a university hospital. More specifically, we aimed to determine the following: (1) the proportion of patients who received clozapine within two years of disease onset, (2) baseline predictors of clozapine use, (3) time from starting the first antipsychotic to clozapine initiation, (4) concomitant medications, and (5) clozapine-related adverse effects. METHODS: All patients admitted to a specialized FEP treatment unit at our hospital between April 2013 and July 2020 were included and followed for two years. The following variables were assessed: baseline sociodemographic characteristics; medications prescribed during follow-up; clozapine-related adverse effects; and baseline predictors of clozapine use. We classified the sample into three groups: clozapine users, clozapine-eligible, and non-treatment resistant (TR). RESULTS: A total of 255 patients were consecutively included. Of these, 20 (7.8%) received clozapine, 57 (22.4%) were clozapine-eligible, and 178 (69.8%) were non-TR. The only significant variable associated with clozapine use at baseline was the Global Assessment of Functioning (GAF) score (R2=0.09, B=-0.07; OR=0.94; 95% CI: 0.88-0.99; p=0.019). The median time to clozapine initiation was 55.0 (93.3) days. The most common side effect was sedation. CONCLUSIONS: A significant proportion (30.2%) of patients in this cohort were treatment resistant and eligible for clozapine. However, only 7.8% of the sample received clozapine, indicating that this medication was underprescribed. A lower baseline GAF score was associated with clozapine use within two years, suggesting that it could be used to facilitate the early identification of patients who will need treatment with clozapine, which could in turn improve treatment outcomes.

Evaluation of major adverse events of clozapine based on accordance to an international titration guideline.

Introduction: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but without appropriate monitoring, it can be associated with potentially fatal outcomes. An International Adult Clozapine Titration Guideline categorizes patients into normal or slow metabolizers. Categorization provides clozapine titration schedules and recommends regular c-reactive protein (CRP) and clozapine concentration monitoring to reduce the risk of adverse drug reactions (ADRs). The impact of the guideline on clozapine ADRs has not been evaluated. Methods: A retrospective chart review assessed clozapine titrations, laboratory monitoring, ADRs, and discontinuations for clozapine-naive adult inpatients at a single center from January 1, 2013, to June 1, 2022. Each patient's cumulative weekly clozapine dosage was compared with their guideline recommended dosage to create a percent accordance. Linear logistic regression evaluated the relationship between titration speed and the presence of an ADR, while descriptive statistics analyzed laboratory monitoring. Results: Forty-three patients were included, with the majority being White males with schizophrenia. An inverse relationship existed between the last inpatient week clozapine dose percent accordance and the probability of an ADR. Nonobese patients were less likely than obese patients to experience an ADR (odds ratio = 0.17; 95% CI, 0.03-0.99). CRP and clozapine concentration monitoring was suboptimal. Discussion: Based on our small retrospective review of primarily White males, more aggressive clozapine titrations did not increase ADRs. Future studies with more diverse samples are needed and should focus on specific ADRs, which may have increased occurrence with rapid titrations. Obese patients were at higher risk of ADRs, correlating with the guideline-recommended slower titrations for these patients.

Impact of traumatic brain injury on risk for schizophrenia and bipolar disorder.

The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.

Severe psychiatric disorders are associated with increased risk of dementia.

BACKGROUND: Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited evidence from longitudinal studies on the role of anxiety, bipolar and psychotic disorders. Electronic health records (EHRs) permit large cohorts to be followed across the lifespan and include a wide range of diagnostic information. OBJECTIVE: To assess the association between four groups of psychiatric disorders (schizophrenia, bipolar disorder/mania, depression and anxiety) with dementia in two large population-based samples with EHR. METHODS: Using EHR on nearly 1 million adult individuals in Wales, and from 228 937 UK Biobank participants, we studied the relationships between schizophrenia, mania/bipolar disorder, depression, anxiety and subsequent risk of dementia. FINDINGS: In Secure Anonymised Information Linkage, there was a steep increase in the incidence of a first diagnosis of psychiatric disorder in the years prior to the diagnosis of dementia, reaching a peak in the year prior to dementia diagnosis for all psychiatric diagnoses. Psychiatric disorders, except anxiety, were highly significantly associated with a subsequent diagnosis of dementia: HRs=2.87, 2.80, 1.63 for schizophrenia, mania/bipolar disorder and depression, respectively. A similar pattern was found in the UK Biobank (HRs=4.46, 3.65, 2.39, respectively) and anxiety was also associated with dementia (HR=1.34). Increased risk of dementia was observed for all ages at onset of psychiatric diagnoses when these were divided into 10-year bins. CONCLUSIONS: Psychiatric disorders are associated with an increased risk of subsequent dementia, with a greater risk of more severe disorders. CLINICAL IMPLICATIONS: A late onset of psychiatric disorders should alert clinicians of possible incipient dementia.

Amisulpride as the antipsychotic of choice in severe psychotic disorder with comorbid impaired glucose tolerance.

Antipsychotics are the mainstay treatment for the majority of severe mental illnesses. Such patients are also more prone to develop medical comorbidities, which complicate the treatment decisions. It is estimated that up to 40% of individuals with schizophrenia have impaired glucose tolerance (IGT) or diabetes, which can be attributed to a combination of genetic, lifestyle, and medication-related factors. Some widely used antipsychotic medications like olanzapine, risperidone, and clozapine have been associated with an increased risk of weight gain, insulin resistance, and other metabolic abnormalities, which can worsen IGT and increase the risk of developing diabetes. Among second-generation antipsychotics (SGAs), amisulpride, aripirazole, and ziprasidone have a fairly low potency to cause obesity and hyperglycemia. In this context, clinicians must balance the benefits and risks of different antipsychotic medications and consider the individual's specific needs and preferences. Here, we shall discuss three cases, to ascertain how the use of amisulpride helped in glycemic control, and also reflect on probable etiologies leading to deranged glucose levels.

Group arts therapies for patients with schizophrenia: a protocol of systematic review and meta-analysis.

INTRODUCTION: Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including numerous side effects, low adherence to medication and substantial costs. In this context, group arts therapies (GATs) emerge as a promising complementary approach for symptom alleviation in schizophrenia patients. Nonetheless, the effectiveness and safety of GATs are yet to be firmly established. This study aims to systematically assess the therapeutic impact of all group-based artistic interventions as complementary treatments for schizophrenia, focusing on their potential benefits. METHODS AND ANALYSIS: This study will search four English-language databases (PubMed, Web of Science, Cochrane Library and Embase), two Chinese databases (Wanfang Data and China National Knowledge Infrastructure) and three Korean databases (RISS, Korean Citation Index and DBpia) from their inception until October 2023. It will include all randomised controlled trials that compare GATs for schizophrenia with standard rehabilitation methods. The primary outcome is the improvement in patients' positive and negative symptoms. Methodologies such as bias risk assessment, data synthesis, sensitivity analysis and subgroup analysis will be implemented using Review Manager V.5.4. Study results with high heterogeneity will be merged using a random-effects model (I 2>50% or p<0.1). In cases where meta-analysis is not viable due to significant clinical and methodological heterogeneity, a qualitative summary of the findings will be provided. ETHICS AND DISSEMINATION: The data used in this systematic review are anonymised, devoid of any private information, eliminating the requirement for ethical approval. Dissemination of the research findings will be conducted via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023471583.

TNIK in disease: from molecular insights to therapeutic prospects.

TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases.

Screening indicators to evaluate the clinical significance of drug-drug interactions in polypharmacy among older adults with psychiatric disorders: a delphi study.

BACKGROUND: Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. METHODS: The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts' opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert's judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. RESULTS: After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary "pharmacodynamic indicator" included "severity of adverse drug reactions", "duration of adverse drug reaction", "symptom relief", "time to onset of symptomatic relief", "number of days in hospital", and "duration of medication". The secondary "pharmacokinetic indicator" contained "dosage administered" and "dosing intervals". The primary "patient tolerance indicator" contained one secondary indicator of "patient tolerability". The primary indicator "patient adherence" contained one secondary indicator of "patient adherence to medication". The primary indicator "cost of drug combination" contained one secondary indicator of "readmission". These indicators were used to determine the clinical significance of DDIs during polypharmacy. CONCLUSIONS: The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.

Psych Unit Gangs: An Autoethnography.

The stigma against people with mental illness is a well-worn subject; however, stigma between groups of people with different mental illnesses is rarely discussed. Within the context of a psychiatric hospital, hierarchies form among patients based on symptomatology and diagnosis. In this perspectives piece, I explore, how, in my experiences with being on the bottom of this hierarchy as a person with a schizophrenia-spectrum psychotic illness in a psychiatric hospital. I, and my fellow "psychotics," were stigmatized and outcasted by other groups of individuals who were diagnosed with mental illnesses that are considered less serious than psychosis. I explore how one stigmatized, outcasted group (people with substance use and mood disorders) construct power relationships over an even more highly stigmatized, marginalized group (people with psychotic disorders). Utilizing Goffmanian and Tajfel theories, the perspective explores stigma within a total institution, and the formation of in-groups and out-groups. I explore how people, upon entering the psychiatric hospital unit, know almost immediately whether they belong to the dominant group or the subordinate group, and I conclude with recommendations to reduce the stigma of psychotic disorders within popular culture.

Diffusion magnetic resonance imaging for treatment response prediction in schizophrenia spectrum disorders: A systematic review.

A substantial portion of schizophrenia spectrum disorder (SSD) patients exhibit resistance to antipsychotic treatments, emphasizing the need for reliable treatment response biomarkers. Previous magnetic resonance imaging (MRI) studies have identified various imaging predictors in SSD. This study focuses on evaluating the effectiveness of diffusion MRI sequences, diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI), in predicting antipsychotic response in SSD patients. A systematic search for relevant articles was conducted in PubMed, Embase, Scopus, and Web of Science on February 11, 2024. Twelve studies involving a total of 742 patients were systematically reviewed. The baseline DTI/DWI biomarkers revealed significant associations with antipsychotic treatment response. Notably a consistent negative link was found between response and baseline fractional anisotropy (FA) in fronto-temporo-limbic white matter tracts, specifically the superior longitudinal fasciculus, providing moderate-level evidence. In addition, weak-level evidence was found for the negative association between the treatment response and baseline FA in the corpus callosum, internal, and external capsule tracts. Collectively, this review demonstrated that obtaining pre-treatment brain diffusion MRI scans, particularly from white matter tracts of fronto-temporo-limbic network, can assist in delineating the treatment response trajectory in patients with SSD. However, additional larger randomized controlled trials are required to further substantiate these findings.

Cognitive behavioural therapy for insomnia (CBT-I) in schizophrenia and schizoaffective disorder: protocol for a randomised controlled trial.

INTRODUCTION: Insomnia is a common symptom among patients with schizophrenia and schizoaffective disorder, negatively impacting symptom severity, functioning and well-being; however, it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy (CBT-I). There is some evidence that CBT-I can also be used to treat insomnia in patients with schizophrenia, but only a few randomised controlled trials (RCTs) have been published. The aim of this ongoing RCT is to determine whether we can alleviate symptoms of insomnia and improve the quality of life in patients with schizophrenia and schizoaffective disorder through CBT-I delivered via the internet or in a group mode. METHODS AND ANALYSES: The aim of this study is to recruit 84-120 outpatients from the Psychosis Clinics of Helsinki University Hospital and the City of Helsinki Health Services. The main inclusion criteria are a diagnosis of schizophrenia or schizoaffective disorder and self-reported sleep problems. The study will be performed on a cyclic basis, with a target of 12-24 patients per cycle. Participants are randomly assigned into three groups: (1) a group receiving only treatment as usual (TAU), (2) internet-based individual therapy for insomnia (iCBT-I)+TAU or (3) group therapy for insomnia (GCBT-I) conducted via a virtual platform+TAU. The primary outcome measures are quantitative changes in the Insomnia Severity Index score and/or changes in health-related quality of life using the 15D quality of life measure. Secondary outcomes include self-reported variables for sleep, health, stress and the severity of psychotic and depressive symptoms; objective outcomes include actigraphy and bed sensor data to evaluate circadian rhythms and motor activity. Outcome measures are assessed at baseline and after the treatment period at weeks 12, 24 and 36. ETHICS AND DISSEMINATION: The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, approved the study protocol. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04144231.

Disengagement from the Ribeirão Preto early intervention program for psychosis: A retrospective cohort study.

BACKGROUND: Treatment discontinuation within Early Intervention Services (EIS) for psychosis poses a significant challenge to achieving better outcomes in the early stages of psychotic disorders. Prevalence and predictors of early disengagement from EIS located in low- and middle-income countries (LMICs) remain poorly investigated. We aimed to examine the rates and predictors of disengagement from the Ribeirão Preto Early Intervention Program for Psychosis (Ribeirão Preto-EIP) in Brazil. METHODS: We conducted a retrospective cohort study using data from patients referred to the Ribeirão Preto-EIP between January 01, 2015, and December 31, 2018. Exclusion criteria were individuals with a single consultation, a diagnosis other than a psychotic disorder, and documented cases of death. RESULTS: Our sample comprised 234 patients, with an overall median follow-up time of 14.2 months. Early treatment disengagement was observed in 26.5 % (n=62), with a median time to disengagement of 5.25 months. Univariable analysis identified non-white skin color (HR=2.10, 95 %CI 1.26-3.49), positive THC screening (HR=2.22, 95 %CI 1.23-4.01), and substance-induced psychosis (HR=2.15, 95 %CI 1.10-4.21) as significant predictors. In multivariable analysis, only non-white skin color remained a significant predictor of early disengagement (HR=1.87, 95 %CI 1.08-3.27). CONCLUSIONS: The observed rates of early disengagement in our sample are similar to those reported in wealthy countries, but higher than previously reported for LMICs. Non-white skin color predicted early disengagement in our sample, probably due to social disadvantages. Our data highlights the need for enhanced research elucidating the specific features of EIS in LMICs.