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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. Methods A sample of 31 healthy controls and 29 patients with FEP were included in this study. Diagnoses were ascertained on the Structured Clinical Interview for DSM-IV-TR. Symptom severity was assessed on the Positive and Negative Syndrome Scale. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay method at recruitment and at 3-, 6-, and 12-month time points. Results Serum BDNF levels in both groups did not differ significantly over time. Baseline BDNF levels in patients with FEP did not correlate with symptom severity and neither baseline BDNF level nor its relative change at 3-month predicted remission status at 6- and 12-month follow-up visits. Of note, we observe similar fluctuations in serum BDNF levels in both patients and healthy controls over the 12-month period. Conclusions Findings from our study did not support a role for serum BDNF as a biomarker for patients with FEP. Because of the polygenic nature of psychosis, we recommend a comprehensive multimarker profile consisting of markers from representative components of mediated neuronal nutrition, neuroimmunology, and neurologic functional deficit to allow for better predictive power.

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.Methods:A sample of 106 healthy controls and 105 ultra-high risk of psychosis individuals from the Longitudinal Youth at Risk Study was included in this study. Ultra-high risk of psychosis status was determined using the Comprehensive Assessment of At-Risk Mental State at recruitment. Calgary Depression Scale for Schizophrenia was used to assess the severity of depression. All participants were followed up for 2 years, and ultra-high risk of psychosis remitters were defined by ultra-high risk of psychosis individuals who no longer fulfilled Comprehensive Assessment of At-Risk Mental State criteria at the end of the study period. Levels of brain-derived neurotrophic factor were measured in the serum by enzyme-linked immunosorbent assay method.Results:The ultra-high risk of psychosis group had significantly higher baseline levels of serum brain-derived neurotrophic factor compared with the control group (3.7 vs 3.3 ng/mL, P=.018). However, baseline levels of serum brain-derived neurotrophic factor did not predict the development of psychosis (OR=0.64, CI=0.40–1.02) or remission (OR=0.83, CI=0.60–1.15) from ultra-high risk of psychosis status.Conclusion:Findings from our study did not support a role for serum brain-derived neurotrophic factor in predicting outcomes in ultra-high risk of psychosis individuals. However, the finding of higher levels of serum brain-derived neurotrophic factor in ultra-high risk of psychosis individuals deserves further study. NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version

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. Methods In this study, HP, A1T and A2M gene expression levels from whole blood were measured at recruitment, 1- and 3-month follow-up visits using quantitative PCR (qPCR) in 43 patients with FEP and in 57 healthy controls. Diagnoses was ascertained on the Structured Clinical Interview for DSM-IV-TR. Severity of symptoms in patients was assessed on the Positive and Negative Syndrome Scale (PANSS) and a previously validated 5-factor PANSS structure was applied in the subsequent analyses. Results The FEP sample comprised of 28 (65.1%) individuals with schizophrenia, 12 (27.9%) with schizophreniform disorder and 3 (7%) with schizoaffective disorder. HP gene expression level was noted to be significantly higher in patients than controls at all three time points: recruitment (P = 0.049), 1-month follow up (P = 0.002) and 3-month follow up (P = 0.005). PANSS positive, depression, and excitement symptom factors showed significant associations with HP (P = 0.002), A1T (P = 0.016) and A2M (P = 0.034), respectively. These findings remained significant after controlling for age, gender, smoking status and accumulated chlorpromazine dosage. Conclusion The current study provides information on HP, A1T and A2M gene expression profiles in FEP patients and their associations with psychopathology. This provides support for the hypothesis that inflammation is related to schizophrenia and further encourages studies on immune-inflammatory markers to understand the relationship between inflammation and schizophrenia.

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. A total of 31 FEP patients and 31 healthy controls were recruited from Institute of Mental Health, Singapore. FEP patients were identified using Structured Clinical Interview for DSM-IV Axis I disorders (SCID-1) and severity symptoms were assessed using the positive and negative syndrome scale (PANSS). Sera from participants were analyzed for total vitamin D, vitamin D-binding protein (DBP) and bioavailable vitamin D. Linear regressions were performed to examine the associations between serum total and bioavailable vitamin D and the PANSS subscales. Current study noted a significantly lower bioavailable vitamin D was in the FEP group and an association between bioavailable vitamin D and negative symptoms in FEP patients in a population with a consistent supply of sun exposure throughout the year.

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. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells.

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. Whole-blood gene expressions from 56 UHR subjects and 28 healthy controls are checked for existence of a consistent gene expression profile (signature) underlying UHR, across a variety of normalization and heterogeneity-removal techniques, including simple log-conversion, quantile normalization, gene fuzzy scoring (GFS), and surrogate variable analysis. During functional analysis, consistent and reproducible identification of important genes depends largely on how data are normalized. Normalization techniques that address sample heterogeneity are superior. The best performer, the unsupervised GFS, produced a strong and concise 12-gene signature, enriched for psychosis-associated genes. Importantly, when applied on random subsets of data, classifiers built with GFS are “meaningful” in the sense that the classifier models built using genes selected after other forms of normalization do not outperform random ones, but GFS-derived classifiers do. Data normalization can present highly disparate interpretations on biological data. Comparative analysis has shown that GFS is efficient at preserving signals while eliminating noise. Using this, we demonstrate confidently that the UHR designation is well correlated with a distinct blood-based gene signature.

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. In this study, GAD67 and GAD25 mRNA levels were measured by quantitative PCR (qPCR) in peripheral blood of subjects with first-episode psychosis (FEP) and from healthy controls. We observed low GAD25 and GAD67 gene expression levels in human peripheral blood. There was no difference in GAD25 and GAD67 gene expression level, and GAD25/GAD67 ratio between patients with FEP and healthy controls. PANSS negative symptoms were associated with levels of GAD25 mRNA transcripts in patients with FEP. While the current study provides information on GAD25 and GAD67 mRNA transcript levels in whole blood of FEP patients, further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.