People with schizophrenia have white matter deficits, according to a recent study. Eventually, these discoveries could lead to the development of new treatments, the researchers hope.
Schizophrenia is a psychiatric disorder that affects 0.7% to 1% of the world’s population. This disease is generally manifested by a disturbed perception of reality, delusions, hallucinations or even social and relational isolation. It is so disabling that in France, at least one out of two patients attempts suicide, according to Inserm. This in part because the treatments are limited and very heavy in side effects.
Indeed, the antipsychotics generally prescribed can cause significant weight gain, fatigue or muscle agitation. One study has even linked first-generation antipsychotics to brain tissue loss in patients with schizophrenia. However, findings recently published in the journal Schizophrenia Bulletin, could lead to a new treatment. Here, the researchers noticed that the patients would present deficits of white matter, the part of the brain comprising the axons which carry nerve impulses between neurons.
In the past, several studies have shown differences in the levels of sphingolipids, fatty molecules that play a role in the formation of myelin, which protects and insulates certain nerve fibers, in schizophrenics. Here, the researchers therefore decided to analyze these levels in the post-mortem brain tissue of 15 patients. Using mass spectrometry, a technique for identifying particles in a sample by measuring their mass, they found that levels of a sphingolipid called S1P were lower in people with schizophrenia.
A deficit specific to schizophrenia
In detail, these levels were lower in a region of the brain called the corpus callosum. Abnormalities in this white matter-rich region can cause communication dysfunction between neurons.
“It was the first psychiatric study of the brain post mortem to use mass spectroscopy analysis, and our discovery would not have been possible without our newly established comprehensive technique for sphingolipid screening”welcomes Dr. Takeo Yoshikawa, team leader at RIKEN CBS (Tokyo, Japan), who conducted the study.
To determine if this dysfunction was common to all mental disorders, scientists also analyzed the brains of people with bipolar disorder and major depression. They then found that the S1P levels in these people were normal. In conclusion, this deficit would be specific to schizophrenia.
Stop the degradation of the sphingolipid S1P
Other later experiments then showed that the problem could be caused by abnormal degradation of S1P and not by impaired production. If so, drugs could be developed to stop S1P degradation and treat schizophrenia. An already existing treatment could also work: fingolimod (Gilenya), used in the treatment of multiple sclerosis. Indeed, it targets S1P, the researchers remind. However, before this is certain, further research is needed to better understand the exact role of S1P in schizophrenia. It will therefore now be a question of working on laboratory animals.
“Because we have no other angle of attack on the causes of schizophrenia, many pharmaceutical companies are withdrawing from the development of drugs related to schizophreniaexplains Doctor Takeo Yoshikawa. We hope that our findings can provide a new angle of approach and a new target for drug development.”
According to Inserm, 600,000 people suffer from schizophrenia in France. The disease most often manifesting itself between the ages of 15 and 25, it is essential to succeed in taking charge of it as soon as possible in order to control the crises. Because if the patients never really recover from schizophrenia, after a few years of treatment, about a third of them manage to resume a normal social, emotional and professional life.
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