Blood Tests for Diagnosis of Schizophrenia and Depression?
Blood Tests for Diagnosis of Schizophrenia and Depression?
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.
Biomarkers search
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.
This is certainly a significant breakthrough for psychiatry, however, we must be careful not to draw too sweeping a conclusion from such research. While the blood test for Schizophrenia has great potential in helping identify patients earlier, I am deeply concerned that developing a blood test for MDD will lead to further short-cutting in the evaluation of patients by psychiatrists. It is prudent to note that the blood test CONFIRMED diagnoses that had previously been determined, but DID NOT CHANGE with medication treatment. This could mean that the individuals were biologically predetermined to develop depression, or, more likely, could indicate that medication alone is not adequate treatment for depression. Recent literature reminds us that the doctor patient relationship is far more important that once believed, when measuring response to treatment. The doctor needs to connect with the patient, adequately evaluate the patient, and pay attention to the social factors that lead to and fuel ongoing depression. We have abdicated the treatment of our patient population to primary care practitioners, alternative practitioners, and non-MD therapists for so long, we are losing touch with the essential roots of our profession. Evaluating and treating patients with depression should involve a detailed interview by the psychiatrist, not a 15 minute once-over and a blood test. Based upon the cost of the test, it is clearly more cost-effective to do the former, rather than the latter, so let us hope that the psychiatric community does not further abdicate its position, now to laboratory scientists!
The depression blood test marketed by Ridge Diagnostics is something of a boondoggle. The two question PHQ-2 test is highly sensitive and specific for depression, and does not cost $745! See my post on this "biomarker" at http://carlatpsychiatry.blogspot.com/2011/08/blood-test-for-depression-r....
The use of blood tests to diagnosed neurological disorders (i.e., psychiatric disorders) is long overdue. I agree that such tests will reduce the negative stigma associated with neurological conditions & the perception that those suffering with such disorders can simply change their behavior or receive conditioning techniques to free themselves from the disorder. The change in perception from the mind model to the neurological condition model will increase one's willingness to use medications to improve neurologic function. Now, if we can eliminate the negative stigma associated with terms such as, psychotic & psychiatric, so many people suffering with neurological conditions will become more open to seeking medical support to treat their symptoms. In the end, psychiatric conditions are neurological disorders because they stem from anomalies in genes/cells that impact brain function.
This mechanistically diverse basket of markers with relevant physiologic underpinnings is quite interesting, especially if it has "85% specificity and sensitivity". I have watched many markers come and go with varying degrees of value. I always come back to the clinical reality, which is the basis for judging the markers value in the end. Brain imaging "markers"(patters of blood flow or activity)have teaching value but are generally of little value in the individual case
The "marker" approach will have more use in genetic counseling and working with family members of mentally ill than with those individuals with established mental illness who could care less about their markers, since they already have the full expression clinically. If the markers (basket of markers) could predict penetrance of illness (which is quite variable) that would be a big deal. It would help define the Cannabis/pychosis risk group.
Robert E. Sands, MD