A biomarker in hair could help diagnose schizophrenia

One of the hardest things when dealing with psychiatric illness is to come up with a clear diagnosis, but it seems that now it might be possible to diagnose schizophrenia just by analysing a certain biomarker in people’s hair.

Mental illness is hard to diagnose
Mental illness. Mural on the Berlin Wall by Chitrapa

In an article recently published in the EMBO Journal of Molecular Medicine 1, a Japanese group of researchers led by Takeo Yoshikawa found that an enzyme responsible for the production of hydrogen sulphide (HS), Mpst, is unregulated in the brains of both mice and human with schizophrenia symptoms like the startle response to stimuli.

But let’s start from the beginning, schizophrenia is a very complex mental illness (so much so that some people consider it not one but an array of diseases), characterised for symptoms ranging from impaired social behaviour to delusions and auditory hallucinations. With a strong genetic component (about 80% of the causality is associated with certain genetic variations), usually an environmental trigger like drug use or emotional trauma will mark the onset of the symptoms. From this variability, it seems pretty obvious that to reach a conclusive diagnosis before the symptomatic stage is complicated. And there is where this biomarker in hair could help diagnose schizophrenia.

Concept of repulse inhibition (PPI) serves in the lab to study the startle response to stimuli. What does PPI involve? When we hear a strong scary noise, we are usually not as startled if we heard another loud similar noise shortly before. That means we have a high PPI. But schizophrenia patients, on the other hand, will be equally startled by the second noise, regardless of the presence of a first “preparing” sound. They have therefore low PPI.

Biomarker in hair could help diagnose schizophrenia
Hair follicles could have the answer…Credit: Popular Science Monthly Volume 71

Like humans, mice also show this PPI, and the researchers found that mice with low PPI (let’s call them schizo-like) had increased levels of expression of the enzyme Mpst. What’s more, reducing the levels of Mpst, also increased the PPI in the affected mice.

But what about Mpst? Does it also have an altered expression in humans affected by schizophrenia? The answer, as shown by the team’s results, is yes. And, not only there is a correlation with increased levels of Mpst in the brain, but also a correlation with the severity of the symptoms experienced during the life of those patients whose brain were examined (postmortem).

Knowing that, the researchers gathered hair follicles from more than 150 people and examined the expression levels of Mpst, finding that those were much higher in people diagnosed with schizophrenia. And this is how a biomarker in hair could help diagnose schizophrenia. Still, Mpst is not a 100% reliable biomarker, possibly because schizophrenia is not one but various diseases, and some patients might have some characteristics that others do not share.

Not only has this discovery the potential of revolutionising disease diagnosis but also the search for novel treatment targets. But the most interesting thing by far is the finding that the cause might be an impaired cell energy metabolism as a result of epigenetic modifications leading to the over expression of Mpst and other anti-oxidative genes. But what is driving these epigenetic changes? It seems that inflammatory/oxidative threats in early brain development could produce an anti-oxidative response mediated by Mpst which would affect cell metabolism and in turn lead to schizophrenia.

In conclusion, a new biomarker in hair could help early diagnosis of -some- schizophrenia cases and offers hope for new drug discovery. Now, only time will tell how far Mpst can take us.

References

  1. M. Ide at al (2019) Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology EMBO Mol Med doi: 10.15252/emmm.201910695

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