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Biomarker for schizophrenia can be detected in human hair

Diagnosing disorders of thought is easier when a reliable and objective marker can be found. In the case of schizophrenia, we have known for more than 30 years that it is associated with an abnormal startle response. Normally, we are not startled as much by a burst of noise if a smaller burst -- called a prepulse -- comes a little bit earlier. This phenomenon is called prepulse inhibition (PPI) because the early pulse inhibits the startle response. In people with schizophrenia, PPI is lowed, meaning that their startle response is not dampened as much as it should be after the prepulse.

The PPI test is a good behavioral marker, and although it cannot directly help us understand the biology behind schizophrenia, it was the starting point that led to current discoveries.

The researchers at RIKEN CBS began first looked for differences in protein expression between strains of mice that exhibit extremely low or extremely high PPI. Ultimately, they found that the enzyme Mpst was expressed much more in the brains of the mouse strain with low PPI than in the strain with high PPI. Knowing that this enzyme helps produce hydrogen sulfide, the team then measured hydrogen sulfide levels and found that they were higher in the low-PPI mice.

"Nobody has ever thought about a causal link between hydrogen sulfide and schizophrenia," says team leader Takeo Toshikawa. "Once we discovered this, we had to figure out how it happens and if these findings in mice would hold true for people with schizophrenia."

[...]

Current treatments for schizophrenia focus on the dopamine and serotonin system in the brain. Because these drugs are not very effective and have side effects, Yoshikawa says that pharmaceutical companies have abandoned the development of new drugs. "A new paradigm is needed for the development of novel drugs," he explains. "Currently, about 30% of patients with schizophrenia are resistant to dopamine D2-receptor antagonist therapy. Our results provide a new principle or paradigm for designing drugs, and we are currently testing whether inhibiting the synthesis of hydrogen sulfide can alleviate symptoms in mouse models of schizophrenia."

Journal Reference:

Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology. EMBO Molecular Medicine, 2019; DOI: 10.15252/emmm.201910695

Original Submission