Nav: Home

Biomarker for schizophrenia can be detected in human hair

October 28, 2019

Working with model mice, post-mortem human brains, and people with schizophrenia, researchers at the RIKEN Center for Brain Science in Japan have discovered that a subtype of schizophrenia is related to abnormally high levels hydrogen sulfide in the brain. Experiments showed that this abnormality likely results from a DNA-modifying reaction during development that lasts throughout life. In addition to providing a new direction for research into drug therapies, higher than normal levels of the hydrogen sulfide-producing enzyme can act as biomarker for this type of schizophrenia.

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."

First, to be sure that Mpst was the culprit, the researchers created an Mpst knockout version of the low-PPI mice and showed that their PPI was higher than that in regular low-PPI mice. Thus, reducing the amount of Mpst helped the mice become more normal. Next, they found that MPST gene expression was indeed higher in postmortem brains from people with schizophrenia than in those from unaffected people. MPST protein levels in these brains also correlated well with the severity of premortem symptoms.

Now the team had enough information to look at MPST expression as a biomarker for schizophrenia. They examined hair follicles from more than 150 people with schizophrenia and found that expression of MPST mRNA was much higher than people without schizophrenia. Even though the results were not perfect--indicating that sulfide stress does not account for all cases of schizophrenia--MPST levels in hair could be a good biomarker for schizophrenia before other symptoms appear.

Whether a person develops schizophrenia is related to both their genetics and the environment. Testing in mice and postmortem brains indicated that high MPST levels were associated with changes in DNA that lead to permanently altered gene expression. So, the next step was for the team to search for environmental factors that could result in permanently increased MPST production.

Because hydrogen sulfide can actually protect against inflammatory stress, the group hypothesized that inflammatory stress during early development might be the root cause. "We found that anti-oxidative markers--including the production of hydrogen sulfide--that compensate against oxidative stress and neuroinflammation during brain development were correlated with MPST levels in the brains of people with schizophrenia," says Yoshikawa.

He proposes that once excess hydrogen sulfide production is primed, it persists throughout life due to permanent epigenetic changes to DNA, leading to "sulfide stress" induced 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."
-end-
This study was published in the journal EMBO Molecular Medicine.

Reference: Ide et al. (2019) Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology. EMBO Molecular Medicine. doi: 10.15252/emmm.201910695.

RIKEN

Related Schizophrenia Articles:

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.
Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.
Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.
The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.
Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.
Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.
Genetics researchers close in on schizophrenia
Researchers at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University have discovered 50 new gene regions that increase the risk of developing schizophrenia.
Looking for the origins of schizophrenia
Schizophrenia may be related to neurodevelopment changes, including brain's inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ).
Researchers uncover novel mechanism behind schizophrenia
An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein--neuregulin 3--controls how key neurotransmitters are released in the brain during schizophrenia.
A new genetic marker for schizophrenia
Japanese scientists find a rare genetic variant that shows strong association with schizophrenia.
More Schizophrenia News and Schizophrenia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.