Identification of a molecular profile associated with immune status in first-onset schizophrenia patients.

Objectives: Alterations in immunological parameters have been reported for schizophrenia although little is known about the effects of inflammatory status on immune-related functional changes at disease onset. Here, we have investigated such T cell-dependent molecular changes in first-onset, antipsychotic-naive schizophrenia patients using a novel ex vivo blood culture system.

Methods: Blood samples from patients (n=17) and controls (n=17) were collected into stimulant-containing or null control TruCulture™ tubes, incubated 24 hours and the concentrations of 107 immune and metabolic molecules measured in the conditioned media using the HumanMAP™ immunoassay system.

Analysis of serum and plasma identifies differences in molecular coverage, measurement variability, and candidate biomarker selection.

Purpose: To compare the use of serum and plasma in multiplex immunoassay analyses of 190 proteins and small molecules, and associated molecular pathways. We also tested whether differences between these biofluids can influence the identification of potential biomarkers in a preliminary study comparing bipolar disorder patients with controls.

Experimental Design: Using multiplexed immunoassay analyses, we compared the measurement levels and interindividual variation of 190 proteins and small molecules between serum and plasma collected from 21 healthy individuals.

Identification of a blood-based biological signature in subjects with psychiatric disorders prior to clinical manifestation.

Objectives: To determine whether a molecular signature is present in blood of patients with psychiatric disorders before manifestation of symptoms.

Methods: Multiplex immunoassay analyses were carried out using serum obtained from two case-control studies of schizophrenia (n = 75) and bipolar disorder (n = 110) patients and their matched controls. The samples were drawn within 1 month before estimated onset of illness.

Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia.

Recently, we showed that the circulating levels of insulin-related peptides and the secretory granule protein chromogranin A were increased in small cohorts of first onset schizophrenia patients. Assuming that this effect was associated with impaired insulin signalling, we investigated the possibility that secretion of other hormones is also affected in schizophrenia. Multiplex immunoassay analysis of 21 hormones and hormone-related molecules was carried out using sera from 236 first and recent onset schizophrenia patients and 230 matched controls.

Validation of a blood-based laboratory test to aid in the confirmation of a diagnosis of schizophrenia.

We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects.

Key factors in evaluating potential clinical biomarkers.

Clinical biomarkers have important differences from exploratory or experimental biomarkers. The introduction of biomarkers into a true clinical situation requires unique considerations of the potential utility of the markers. In contrast to experimental situations in which various parameters can be tightly controlled, the world of patient care can be characterized as the 'Wild West' - an unknown frontier in which every possible variable may be introduced at some stage.