Newly developed blood tests for schizophrenia and for depression designed to augment current diagnostic approaches have attracted increased attention at recent major scientific meetings.
At this year’s American Psychiatric Association’s annual meeting in Hawaii, Professor Sabine Bahn, MD, PhD, MRCPsych, Director of the Cambridge Centre for Neuropsychiatric Research (CCNR) and Director/Cofounder of Psynova Neurotech Ltd, described her 15-year search for biomarkers of neuropsychiatric disorders and the development of VeriPsych—reportedly the first blood-based diagnostic test to confirm the presence of recent-onset schizophrenia. It is not a genetic test, but rather an automated test that uses a single serum sample to identify 51 protein biomarkers. It is designed to help mental health professionals arrive at a diagnosis.
Psynova Neurotech, established in 2005 by Bahn and Chris Lowe, PhD, Director of Cambridge University’s Institute of Biotechnology, is a spin-off company created to commercialize CCNR’s findings. Psynova then partnered with the Rules-Based Med-icine (RBM) of Austin, Tex, a CLIA-certified testing laboratory known for its Multi-Analyte Profiling technology platform. In recent months, Psynova Neurotech became a wholly owned subsidiary of RBM, and RBM became a wholly owned subsidiary of Myriad Genetics, taking the name Myriad RBM, Inc.
For Bahn, who is also Chair of Translational Neuroscience at Erasmus Medical Centre in Rotterdam, the Netherlands, the search for biomarkers in psychiatric disorders is a personal pursuit. Her father had bipolar disorder.
Biomarkers have multiple applications, Bahn explained to APA attendees. These include the identification of high-risk individuals and disease subgroups that could serve as target populations for intervention trials; facilitation of “objective” diagnosis; monitoring of patient response to drug treatments; and assessment of patient compliance.
According to Bahn, she and the more than 20 scientists at CCNR are seeking to develop molecular diagnostics for major neuropsychiatric disorders and to determine the cellular mechanisms that regulate the expression of biomarker molecules altered in these states so as to develop novel therapeutic approaches.
CCNR’s lab, she said, uses ad-vanced molecular profiling techniques (microarrays, proteomics, lipidomics, and metabolomics) to globally investigate abnormalities in gene/protein/metabolite/lipid “expression” in postmortem human brain tissue and in blood and other samples derived from patients and matched controls, to establish evidence-based hypotheses.
For example, Bahn told APA attendees that in the team’s examination of postmortem brain tissue of patients with schizophrenia, they found evidence of abnormal glucose utilization. Schizophrenia, she said, might be considered “diabetes of the brain.”
Bahn and her team then moved to cerebrospinal fluid (CSF) in living patients “to see if we could identify the same changes as seen in the postmortem brain.”
The team studied CSF samples from drug-naive or minimally treated patients with first-onset paranoid schizophrenia and demographically matched healthy controls.1
“Our findings suggest alterations in glucoregulatory processes in CSF of drug-naive patients with first-onset schizophrenia. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected,” she said.
Bahn’s team discovered a set of 51 biomarkers with linkages to schizophrenia and to various biochemical pathways, including inflammation and metabolism, as well as cell-to-cell signaling.
The results also suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response and/or outcome.
Eventually, the team moved to using its molecular profiling techniques on blood serum.
During the developmental stage of VeriPsych, 200 biomarker candidates were looked at to assess their connection to schizophrenia. Bahn’s team discovered a set of 51 biomarkers with linkages to schizophrenia and to various biochemical pathways, including inflammation and metabolism, as well as cell-to-cell signaling.
In a subsequent study, the 51 biomarkers were validated in com-bination with a mathematical pro-cess to separate patients with schizophrenia from normal controls.2 The study included analysis of more than 800 blood samples. The panel of 51 markers yielded an average sensitivity and specificity of 85% or greater across 5 clinical centers, according to Bahn.
1. Holmes E, Tsang TM, Huang JT, et al. Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Med. 2006;3:e327.
2. Schwarz E, Izmailov R, Spain M, et al. Validation of a blood-based laboratory test to aid in the confirmation of a diagnosis of schizophrenia. Biomark Insights. 2010;5:39-47.
3. Schwarz E, Guest PC, Rahmoune H, et al. Identification of a biological signature for schizophrenia in serum. Mol Psychiatry. 2011 Apr 12; [Epub ahead of print].
4. Ridge Diagnostics. Improving the Diagnosis of Major Depressive Disorder: a New Multi-Analyte Biomarker Panel and MDDScore. October 18, 2010.