A newly discovered biomarker (something that signals the presence of a disease) in human hair may be related to a subtype of schizophrenia, providing new insight into the condition. This could help with early identification before symptoms set in.
Researchers in Japan have identified higher-than-normal levels of Mpst, an enzyme responsible for producing hydrogen sulfide in the brain, in people with schizophrenia. This abnormality is likely the result of a physiological reaction to certain stressors throughout life that results in modifying DNA, wrote scientists in EMBO Molecular Medicine.
Schizophrenia is a complex mental health diagnosis and has been at the center of numerous studies since its discovery in 1911. The term defines a mental disorder that loosely encompasses a range of symptoms and behaviors, including delusions, hallucinations, and psychosis. It has been linked to a number of potential causes like gut bacteria and being creative. This disorder can be triggered by something as simple as a cat scratch or cannabis use (though the latter can be a chicken-or-the-egg argument). Research suggests that schizophrenia is not one disease but eight disorders with genetically distinct causes with nearly 80 percent of the risk factor being genetic.
One method of diagnosing schizophrenia is a phenomenon known as prepulse inhibition (PPI), which examines a person’s startle response to stimuli. People who do not have schizophrenia are less likely to be startled by a loud noise if there is a precursor. For example, the crackling of a campfire will lessen a person’s response to a louder fire-related sound later. But people with schizophrenia have a lower PPI, meaning that preceding sounds do not lessen their reaction to later ones.
Researchers used the concept of PPI to analyze differences in the expression of certain proteins in mice with low and extremely high PPI. They found that the enzyme Mpst had higher expression in the brains of mice with low PPI. Reducing the level of Mpst also helped the mice to have more “normal” levels of PPI.
"Nobody has ever thought about a causal link between hydrogen sulfide and schizophrenia," said research lead Takeo Yoshikawa in a statement. "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."
The team then examined the postmortem brains of people who had schizophrenia and found that Mpst gene expression was higher than in those without. Levels of Mpst also correlated with the severity of symptoms that a person experienced during their lifetime.
With that information, researchers then examined the hair follicles of more than 150 people with schizophrenia and found that the expression of Mpst was much higher in people with the disease. Although Mpst levels do not account for all cases, they say it could serve as a biomarker for schizophrenia before symptoms appear.
Diagnosing and predicting whether a person has or will develop schizophrenia can be difficult and tedious given its complex symptoms.
“A new paradigm is needed for the development of novel drugs," said Yoshikawa. "Currently, about 30 percent 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."
Understanding the causes of the disease and potential biomarkers can help inform how it is treated. Current methods focus on dopamine and serotonin levels in the brain, but are not very effective and can have a varying degree of side effects.