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.

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.

RNA-sequencing of peripheral whole blood of individuals at ultra-high-risk for psychosis - A longitudinal perspective.

Background: The peripheral blood is an attractive source of prognostic biomarkers for psychosis conversion. There is limited research on the transcriptomic changes associated with psychosis conversion in the peripheral whole blood.

Study Design: We performed RNA-sequencing of peripheral whole blood from 65 ultra-high-risk (UHR) participants and 70 healthy control participants recruited in the Longitudinal Youth-at-Risk Study (LYRIKS) cohort.

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.

DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia.

The essential role of the Reelin gene (RELN) during brain development makes it a prominent candidate in human epigenetic studies of Schizophrenia. Previous literature has reported differing levels of DNA methylation (DNAm) in patients with psychosis. Therefore, this study aimed to (1) examine and compare RELN DNAm levels in subjects at different stages of psychosis cross-sectionally, (2) analyse the effect of antipsychotics (AP) on DNAm, and (3) evaluate the effectiveness and applicability of RELN promoter DNAm as a possible biological-based marker for symptom severity in psychosis.

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.

A Longitudinal Study of Serum Brain-Derived Neurotrophic Factor Levels in First-Episode Schizophrenia.

Background: Biomarkers identified for psychosis might allow for early diagnosis, more accurate prognosis, and tailored individualized interventions. Brain-derived neurotrophic factor (BDNF) is suggested to be a likely candidate biomarker for the diagnosis and treatment evaluation in psychosis. The aims of present study were to examine the levels of serum BDNF in both patients with first-episode psychosis (FEP) and in healthy controls for a year, and to investigate the association between BDNF with symptom severity and remission status.

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.

Levels of Serum Brain-Derived Neurotropic Factor in Individuals at Ultra-High Risk for Psychosis-Findings from the Longitudinal Youth at Risk Study (LYRIKS).

Background: Identifying biomarkers to enrich prognostication and risk predictions in individuals at high risk of developing psychosis will enable stratified early intervention efforts. Brain-derived neurotrophic factor has been widely studied in schizophrenia and in first-episode psychosis with promising results. The aim of this study was to examine the levels of serum brain-derived neurotrophic factor between healthy controls and individuals with ultra-high risk of psychosis.

Peripheral blood gene expression of acute phase proteins in people with first episode psychosis.

Background: There is a growing interest in the association between schizophrenia and the activation of inflammatory system with signs of acute phase (AP) response. Majority of such studies had focused on C-reactive protein (CRP). The aims of the present study were (i) to examine the gene expression profiles of other acute phase proteins (APP), namely haptoglobin (HP), alpha-1 antitrypsin (A1T), and alpha-2 macroglobulin (A2M) in patients with first episode psychosis (FEP) over a period of three months and (ii) to explore the association between APP levels and severity of symptoms.

GAD1 Gene Expression in Blood of Patients with First-Episode Psychosis.

γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter, has often been studied in relation to its role in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), derived from two genes, GAD1 and GAD2. GAD1 is expressed as both GAD67 and GAD25 mRNA transcripts with the former reported to have a lower expression level in schizophrenia compared to healthy controls and latter was reported to be predominantly expressed fetally, suggesting a role in developmental process.

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.

Predicting chemotherapeutic drug combinations through gene network profiling.

Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks.

Genetic and/or non-genetic causes for inter-individual and inter-cellular variability in transporter protein expression: implications for understanding drug efficacy and toxicity.

Introduction: Drug transporters are differentially expressed in many polarized tissues. The varied distribution and expression of transporters determines the net transcellular transport and influences the disposition of many clinically used drugs. ATP-binding cassette (ABC) and Solute Carrier (SLC) transporters interact dynamically to mediate the passage of drugs across cells.

Ensuring good quality RNA for quantitative real-time PCR isolated from renal proximal tubular cells using laser capture microdissection.

Background: In order to provide gene expression profiles of different cell types, the primary step is to isolate the specific cells of interest via laser capture microdissection (LCM), followed by extraction of good quality total RNA sufficient for quantitative real-time polymerase chain reaction (qPCR) analysis. This LCM-qPCR strategy has allowed numerous gene expression studies on specific cell populations, providing valuable insights into specific cellular changes in diseases. However, such strategy imposed challenges as cells of interests are often available in limited quantities and quality of RNA may be compromised during long periods of time spent on collection of cells and extraction of total RNA; therefore, it is crucial that protocols for sample preparation should be optimised according to different cell populations.

Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects.

Aims: This study evaluated the pharmacokinetics of gabapentin in Chinese subjects who received a diet rich in shiitake mushrooms. Shiitake mushrooms have been shown to contain high amount of ergothioneine. In vitro studies have shown that OCTN1-mediated secretion of gabapentin is trans-stimulated by ergothioneine.

Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore.

Novel organic cation transporter 2 (OCTN2) is a multispecific, bidirectional, pH-dependent organic cation transporter. It can function as a carnitine co-transporter with higher affinity for carnitine than OCTN1 but also functions as a uniporter for other cations. Drugs such as verapamil, pyrilamine and beta-lactam antibiotics have been characterized as substrates of OCTN2 and/or inhibitors of carnitine transport.

Genetic variations of the SLC22A4 gene in Chinese and Indian populations of Singapore.

The novel organic cation transporter 1 (OCTN1) is a multispecific, bidirectional and pH-dependent organic cation transporter with low carnitine transport activity. It is a transporter of the physiological substance ergothioneine and mediates the transport of a variety of organic cations such as tetraethylammonium, pyrilamine and quinidine. This study identifies genetic variations of the SLC22A4 gene in two distinct ethnic groups of the Singaporean population (n=192) by DNA sequencing.

Genetic variations of the SLCO1B1 gene in the Chinese, Malay and Indian populations of Singapore.

OATP1B1 is a liver-specific transporter that mediates the uptake of various endogenous and exogenous compounds including many clinically used drugs from blood into hepatocytes. This study aims to identify genetic variations of SLCO1B1 gene in three distinct ethnic groups of the Singaporean population (n=288). The coding region of the gene encoding the transporter protein was screened for genetic variations in the study population by denaturing high-performance liquid chromatography and DNA sequencing.

Genetic variations of the ABCC2 gene in the Chinese, Malay, and Indian populations of Singapore.

MRP2 is a drug transporter that is responsible for the gastrointestinal absorption and biliary excretion of a wide variety of endogenous and xenobiotic compounds, including many clinically used drugs. This study aims to identify genetic variations of ABCC2 gene in three distinct ethnic groups of the Singaporean population (n = 288). The coding region of the gene encoding the transporter protein was screened for genetic variations in the study population by denaturing high-performance liquid chromatography and DNA sequencing.