Author Interviews, Biomarkers, Schizophrenia / 29.10.2019
Subtype of Schizophrenia Can Be Identified by Enzyme in Hair
MedicalResearch.com Interview with:
Dr. Takeo Yoshikawa MD PhD
RIKEN Center for Brain Science
Japan
MedicalResearch.com: What is the background for this study? What are the main findings?
- Currently available drugs for schizophrenia are the dopamine D2 receptor blockers. These compounds were serendipitously discovered over half-century ago. But about 30% of schizophrenia are resistant to the dopamine D2 receptor blockers. In spite of these conditions, pharmaceutical companies have abandoned the development of new drugs. This is because we do not know the principle of drug design.
- Therefore, we need to understand the molecular underpinning of as-yet unknown schizophrenia pathophysiology. Schizophrenia is diagnosed by only patients’ symptoms, not by biological examination. To search for biological underpinning for schizophrenia using experimental animals, we thought that we should examine an endophenotype (biological trait) relevant to schizophrenia. Then we targeted prepulse (PPI) performance.
- Here, dampened PPI is considered as a biological marker of psychiatric disorders, typically of schizophrenia. Importantly, PPI can be measured using the same behavioral paradigm between experimental animals and human.
- C57BL/6 (B6) inbred mouse shows higher (better) prepulse inhibition (PPI) performance, while C3H/He (C3H) inbred mouse shows lowered (worse ) PPI. We premised that C3H mouse is “schizophrenia-prone” and B6 is not. To know the molecular basis for differential PPI levels between the two inbred mouse strains, we performed comprehensive protein expression level analysis (proteomics analysis) using the brains of B6 and C3H mice.
- The expression levels of Mpst, a hydrogen sulfide (H2S)-producing enzyme, is elevated in C3H mouse compared to B6 mouse. Biochemical analysis also supported the elevated H2S production in C3H mouse compared to B6.
- The examination of human samples including postmortem brains, iPS-derived neural stem cells (neurospheres) and hair follicle cells, gave evidence that H2S production system is indeed up-regulated in schizophrenia.