Blood test for schizophrenia? Eur Arch Psychiatry Clin Neurosci Sept 2012

16.10.12

Are we anywhere close to a diagnostic blood test ( or series of tests) for schizophrenia?

This article suggests that work is progressing in this area. Biomarker research is thought to be  one of the main factors driving psychiatric drug development in the next 50 years (FDA).In the early 1980s, the niacin test (attenuated flush response of schizophrenia patients to cutaneous application of niacin) found limited application to support the diagnosis of schizophrenia.Genomic, proteomic and immunoassay technologies are being put together to measure hundreds of biomarkers of relevance in schizophrenia. We now know more about  metabolic, immune and hormonal alterations  in blood in schizophrenia. The individual molecular changes show low effect size ,but combined, it is possible that predictions could be made.

Examples of metabolic changes:  At the molecular level, high fasting glucose and insulin levels, and insulin resistance , increased levels of circulating leptin,impaired glycolytic response has been found in peripheral blood mononuclear cells.Baseline insulin levels were found to predict reduction in negative symptoms and increased body weight . Also, baseline levels of leptin and insulin-related peptides have been identified as predictors of relapse time in patients treated with antipsychotics.

Immune changes: The data suggest activation of monocytes, with increased levels of CCL2, IL-1, IL-6 and TNF-a. An imbalance between the cellular and humoral immune responses has been identified, but the direction of this imbalance is not clear.High levels of C-reactive protein have been associated with symptom severity in schizophrenia.

Hormonal changes : HPA axis dysfunction indicated by high cortisol, ACTH and prolactin levels has been observed. Following treatment with atypical antipsychotic medication, cortisol and prolactin levels have been shown to decrease.

This team of researchers (from Cambridge and Netherlands)  attempted to identify a schizophrenia-specific signature by comparing molecular profiles in sera from schizophrenia patients with matched controls. They used a high- throughput multiplex immunoassay platform targeting 181 blood markers using sera from 250 first- and recent-onset schizophrenia patients and 230 controls matched for age and gender were collected from 4 independent clinical centres in Germany.This experiment resulted in identification of 22 molecules, which were reproducibly changed in schizophrenia across different cohorts.In the second stage, assays for these 22 molecules were combined with those for 29 molecules identified in other studies, and these were validated using 577 samples from a separate cohort of schizophrenia patients and controls.This cohort was used to reflect the patient population normally encountered in clinical practice. The developed classifiers discriminated schizophrenia patients from controls with 83 % accuracy.The biomarker panel was  later retested and decision rules were adjusted for 40 assays.  Integration of signals from multiple molecules was necessary to achieve clinically useful classification accuracy, reflecting the low effect sizes of individual items. This lead to the commercial test,VeriPsychTM,  launched by Psynova Neurotech in collaboration with Myriad-RBM, in October 2010. The test is developed by a single laboratory and intended for use only within this laboratory.It is being evaluated in several clinical sites. In USA it costs $2500 .

Authors also report that they recently identified 20 molecules which were altered 1 month prior to clinical manifestation of schizophrenia discussing the benefits of early diagnosis.The authors consider the implications for further drug development and use of the biomarker data in choosing medications as future possibilities.

Limitations: Authors do not present the sensitivity /specificity data for this test. There is no discussion regarding the appropriate methodology to check whether this test is useful clinically. Authors affiliation to the labs/company is another fact to consider while making conclusions.

This is the summary of the article: Blood test for schizophrenia. Tomasik J, Schwarz E, Guest PC, Bahn S.

Eur Arch Psychiatry Clin Neurosci. 2012

2 thoughts on “Blood test for schizophrenia? Eur Arch Psychiatry Clin Neurosci Sept 2012

  1. Even with atypical antipsychotic medication, there are side effects related to high serum prolactin levels.so , it is strange that the increased prolactin levels in premedicated schizophrenic patients actually decreased after medication.

    • The article says ‘Following treatment with atypical antipsychotic medication, cortisol and prolactin levels have been shown to decrease”. The reference for this ( Markianos M et al (1999) Switch from neuroleptics to clozapine does not influence pituitary-gonadal axis hormone levels in male schizophrenic patients. Eur Neuropsychopharmacol 9:533–536) is actually describing a decrease in prolactin levels when clozapine was started in patients who were already on first gen antipsychotics. You are right in pointing out the clumsiness in this. Thanks.M

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