Schizophrenia linked to irregular fatty metabolism in the brain

Schizophrenia linked to irregular fatty metabolism in the brain. A discovery made by experts at the RIKEN Center for Brian Science (CBS) in Japan has the potential to improve treatments for schizophrenia. The researchers have linked the disorder to a deficiency of fatty molecules found in the white matter of the brain. 

A postmortem comparison showed that schizophrenia was associated with lower levels of S1P, a fatty molecule that is necessary for the production of highly specialized neural cells called oligodendrocytes. 

Existing treatments for schizophrenia, which primarily target dopamine, are not effective for many patients. Schizophrenia linked to irregular fatty metabolism in the brain

“Because we don’t have another angle on what causes schizophrenia, many pharmaceutical companies are pulling out of schizophrenia-related drug development,” said RIKEN CBS team leader Takeo Yoshikawa. “Hopefully, our findings can provide the new angle with a new target for drug development.”

The effects of schizophrenia on the brain are not entirely understood. It is known that people suffering from the disorder have less white matter than normal brains.

White matter is made up of fatty substances formed by oligodendrocytes, specialized cells that are regulated by S1P. The interaction between these specialized cells and neurons are critical for communication within the central nervous system. 

Schizophrenia is characterized by hallucinations and the inability to distinguish fantasy from reality. These symptoms may originate in white matter abnormalities that disrupt communication between neurons.

The RIKEN CBS team conducted a postmortem analysis of the large white matter tract that connects the left and right sides of the brain. The experts found a severe deficiency in S1P fatty molecules, which are needed for the creation of oligodendrocytes.

The study revealed that normal amounts of S1P had been initially produced, but many of these fatty molecules had metabolized and degraded. 

“Drugs that prevent S1P degradation could be particularly effective in treating schizophrenia,” said study first author Kayoko Esaki, who contributed his expertise in the technique of mass spectrometry to measure S1P levels.

“This was the first psychiatric study of the postmortem brain to use mass spectroscopic analysis, and our discovery would not have been possible without our newly established comprehensive technique for screening sphingolipids,” said Yoshikawa.

Further analysis revealed that the postmortem brains of people with bipolar disorder or major depressive disorder did not have abnormal levels of S1P, indicating that the deficiency is specific to schizophrenia.

“The next important step is to determine precisely which S1P receptor-acting drugs are effective in experimental animals,” explained Yoshikawa. “Although the new blockbuster drug fingolimod works at the S1P receptor and is effective at treating multiple sclerosis, we do not yet know how effective it would be for schizophrenia.”

The study is published in the journal Schizophrenia Bulletin.

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By Chrissy Sexton, Earth.com Staff Writer