Blood-spot tests yield potential schizophrenia biomarkers


By Anne Harding

NEW YORK (Reuters Health) - Decades-old dried blood spots from newborns show differences in protein markers between individuals who did versus those who did not go on to develop schizophrenia, according to new findings published in Translational Psychiatry.

“We just wanted to test the feasibility,” Dr. Sabine Bahn, the director of the Cambridge Centre for Neuropsychiatric Research at the University of Cambridge in the UK, told Reuters Health in a telephone interview. “The question was ‘Can you identify the protein markers which we identified in adults?’” The findings did show some overlap between markers seen in newborns who would go on to develop schizophrenia and adults with the condition, indicating “very subtle changes” in metabolism and immune system function, she added.

Denmark, Sweden and Norway archive results of newborn blood spot (NBS) tests, used to screen neonates for metabolic disorders, in their entire populations, Dr. Bahn noted. These so-called “biobanks” are a rich source of information, but immunology techniques have limited effectiveness in studying them, because proteins in the samples degrade over time.

Dr. Bahn and her team used multiple reaction monitoring (MRM), a type of mass spectrometry that can identify prespecified peptides from small samples. However, the researcher noted, MRM mass spectrometry had not previously been used in samples more than six months old, and the blood spots analyzed were collected from 1975 to 1985.

The researchers quantified levels of 77 proteins in 60 antipsychotic-naive patients experiencing their first schizophrenia episode - and in 77 controls with no history of inpatient psychiatric admission.

Differences in abundance (between patients and controls) were present for 14 of the proteins, 13 of which had previously been associated with schizophrenia. After statistical adjustment, the differences were significant for three haptoglobin peptides and one plasma protease C1 inhibitor peptide.

The researchers also measured the 14 proteins in NBS samples from Swedish infants born from 1975 to 1985, including 75 who went on to develop schizophrenia and 644 controls. Three of the 12 proteins that could be analyzed - alpha-2-antiplasmin, complement C4-A and antithrombin-III - differed significantly in their abundance at birth and after schizophrenia onset, compared to their abundance in the control samples.

The NBS also showed significant differences in the abundance of 24 proteins between infants from urban versus those from rural areas.

MRM mass spectrometry is less expensive than immunology techniques, aside from the cost of a mass spectrometry machine, which most hospitals already have, Dr. Bahn noted. In studies using MRM mass spectrometry, she added, participants can collect a blood-spot sample themselves and ship it to researchers by regular mail - at a cost of $10, compared with $600 for shipping a conventional sample on dry ice.

She and her colleagues are currently conducting a study in 3,000 patients to identify a biomarker panel to distinguish between unipolar and bipolar depression.

Eventually, according to Dr. Bahn, it may be possible to use NBS tests to identify patients with psychiatric diagnoses, such as severe autism or schizophrenia, in which earlier diagnosis and treatment can improve outcomes.

Dr. Bahn is a director of Psynova Neurotech Ltd and PsyOmics Ltd, both University of Cambridge spinouts that she helped found to develop and commercialize biomarkers for psychiatric diseases.


Transl Psychiatry 2017.

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