Predicting antipsychotic responsiveness using a machine learning classifier trained on plasma levels of inflammatory markers in schizophrenia.

We apply machine learning techniques to navigate the multifaceted landscape of schizophrenia. Our method entails the development of predictive models, emphasizing peripheral inflammatory biomarkers, which are classified into treatment response subgroups: antipsychotic-responsive, clozapine-responsive, and clozapine-resistant. The cohort comprises 146 schizophrenia patients (49 antipsychotics-responsive, 68 clozapine-responsive, 29 clozapine-resistant) and 49 healthy controls.

Immunophenotyping schizophrenia subtypes stratified by antipsychotic response.

Immune dysfunction has been proposed to play a role in the pathophysiology behind the development and persistence of psychosis. Current immunophenotyping studies are limited by small sample sizes and the number of immune markers investigated. Pharmacological subtypes in schizophrenia based on antipsychotic response have been proposed, but few studies have investigated immunophenotypes in treatment-resistant schizophrenia.

Association between treatment resistance and cognitive function in schizophrenia.

Introduction: Treatment-resistant schizophrenia (TRS) affects around 30% of individuals with schizophrenia. About half of the patients with TRS who are treated with clozapine do not show a meaningful clinical response, that is, clozapine resistance. To date, the relationship between cognitive function and treatment response categories is not entirely clear.

Predictors of functioning in treatment-resistant schizophrenia: the role of negative symptoms and neurocognition.

Introduction: Predictors of functioning are well-studied in schizophrenia, but much less so in treatment-resistant schizophrenia (TRS). In this study, we aim to investigate contributions of schizophrenia symptom domains and neurocognition to predict functioning in a TRS population (n = 146).

Methods: Participants were assessed on the Positive and Negative Syndrome Scale (PANSS), to calculate scores for five symptom factors (Positive, Negative, Cognitive, Depressive and Hostility) and two negative symptom constructs (Diminished Expressivity (DE), and Social Anhedonia (SA) as part of the Motivation and Pleasure-related dimension), based on a previously validated model, modified in accordance with EPA guidelines on negative symptoms assessment.

Deconstructing the genetic architecture of treatment-resistant schizophrenia in East Asian ancestry.

Background: Treatment-resistant schizophrenia (TRS) affects a substantial proportion of patients who do not respond adequately to antipsychotic medications, yet the underlying biological mechanism remains poorly understood. This study investigates the link between the genetic predisposition to schizophrenia and TRS.

Methods: 857 individuals diagnosed with schizophrenia were divided into TRS (n = 142) and non-TRS (n = 715) based on well-defined TRS criteria.

Obsessive-compulsive symptoms and disorder in clozapine-treated schizophrenia.

Background: Obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) are commonly reported in patients with schizophrenia. Furthermore, the use of clozapine in treatment-resistant schizophrenia has been thought to induce or aggravate these disorders. To date, there is a paucity of research regarding the prevalence and associated factors.

Once-daily versus divided dosing regimens of clozapine: A cross-sectional study in Singapore.

Introduction: Clozapine is recognized as the gold standard medication for treatment-resistant schizophrenia. Despite the general recommendation of administering in a divided dosing regimen, clozapine is often prescribed once daily at night in clinical practice. This study aims to compare patient characteristics, psychiatric symptoms, side effects, and plasma concentration of clozapine between once-daily dosing and divided dosing regimens.

The Impact of Clozapine Delay on Clinical Outcomes in Schizophrenia.

Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes. This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks.

Metabolic syndrome and cardiovascular risk between clozapine and non-clozapine antipsychotic users with schizophrenia.

Introduction: Clozapine use is associated with higher risks of metabolic side effects and cardiovascular diseases (CVD). Thus, this study aims to establish and compare the cardiometabolic profiles between non-clozapine antipsychotic and clozapine users with schizophrenia.

Methods: Data from 88 non-clozapine and 166 clozapine users were extracted from existing databases - demographics, medications, smoking and medical histories, anthropometric parameters, serum lipid and fasting glucose levels.

Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia.

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE).

Predicting Real-World Functioning in Schizophrenia: The Relative Contributions of Neurocognition, Functional Capacity, and Negative Symptoms.

Neurocognition and functional capacity are commonly reported predictors of real-world functioning in schizophrenia. However, the additional impact of negative symptoms, specifically its subdomains, i.e.

Correction: Progressive decline in hippocampal CA1 volume in individuals at ultra-high-risk for psychosis who do not remit: findings from the longitudinal youth at risk study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Can Peripheral Blood-Derived Gene Expressions Characterize Individuals at Ultra-high Risk for Psychosis?

The ultra-high risk (UHR) state was originally conceived to identify individuals at imminent risk of developing psychosis. Although recent studies have suggested that most individuals designated UHR do not, they constitute a distinctive group, exhibiting cognitive and functional impairments alongside multiple psychiatric morbidities. UHR characterization using molecular markers may improve understanding, provide novel insight into pathophysiology, and perhaps improve psychosis prediction reliability.

Longitudinal Cognitive Changes in Young Individuals at Ultrahigh Risk for Psychosis.

Importance: Cognitive deficits are a key feature of risk for psychosis. Longitudinal changes in cognitive architecture may be associated with the social and occupational functioning in young people.

Objectives: To examine longitudinal profiles of cognition in individuals at ultrahigh risk (UHR) for psychosis, compared with healthy controls, and to investigate the association of cognition with functioning.

Montreal Cognitive Assessment as a screening instrument for cognitive impairments in schizophrenia.

Background: Cognitive impairment is one of the core features of schizophrenia. For its evaluation, current clinical practice relies on detailed neuropsychological batteries which require trained testers and considerable amount of time to administer. Therefore, a brief and reliable screening tool for identification of overall cognitive impairment prior to a detailed comprehensive neurocognitive assessment is needed in a busy clinical setting.

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials).

Progressive Decline in Hippocampal CA1 Volume in Individuals at Ultra-High-Risk for Psychosis Who Do Not Remit: Findings from the Longitudinal Youth at Risk Study.

Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia.

Association between serum levels of bioavailable vitamin D and negative symptoms in first-episode psychosis.

Total vitamin D levels had been commonly reported to be lowered in patients with chronic psychotic illnesses in countries from the higher latitudes. However, studies on patients with first episode psychosis (FEP) are limited. In this study we investigated serum concentrations of total and bioavailable vitamin D levels in FEP patients compared to healthy controls and the association between symptom severity and vitamin D components.

Investigation of cigarette smoking among male schizophrenia patients.

Male schizophrenia patients are known to have a heavier smoking pattern compared with the general population. However, the mechanism for this association is not known, though hypothesis that smoking could alleviate symptomatology of schizophrenia and reduce side effects of antipsychotics has been suggested. The aims of this study were to validate the heavier smoking pattern among male schizophrenia patients and to investigate the possible mechanisms for the association.