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Betaine supplement reduces schizophrenic behaviours in mice

A new study found that betaine supplementations given to mice reduced schizophrenic behaviours, indicating a drug target.

New research shows that betaine supplementation can counteract psychiatric symptoms in mice. The team from the RIKEN Center for Brain Science (CBS) who conducted the study believe that betaine could be considered as a therapy for psychiatric conditions.

Betaine comes from a normal diet but is also synthesised in the body where it contributes to metabolism in various ways, including as an anti-inflammatory agent. Levels of betaine (glycine betaine or trimethylglycine) in the blood plasma of schizophrenic patients have been found to be low, suggesting it as a possible therapeutic target.

In the new study, mice missing the Chdh gene, involved in making betaine, showed depressive behaviours and greatly reduced betaine levels in both the brain and blood. Levels in the brain recovered when given to the mice as a supplement in drinking water, demonstrating that betaine can pass through the blood-brain barrier.

Psychedelic drugs like PCP and methamphetamine can also produce schizophrenia-like behaviours in both humans and mice. The researchers tested whether betaine supplementation could help alleviate symptoms induced by PCP and methamphetamine in mice. They found that betaine improved cognitive deficits and reversed oxidative stress at the molecular level. Oxidative stress is thought to be one mechanism through which these drugs cause psychiatric symptoms in humans.

Finally, investigation of post-mortem human brain samples showed reduced betaine levels in patients with schizophrenia. They found a subset of brains with “betaine-deficit oxidative stress”, a pathology that occurred in cases with severe psychotic symptoms. The researchers were able to replicate this pathology in induced pluripotent stem cells that simulate the oxidative stress condition and counteract it with the betaine treatment.

“We suggest that one of betaine’s functions is to promote antioxidant activity in the metabolic cycles in which it participates,” says senior author Takeo Yoshikawa. “However, supplementation of betaine is not a silver bullet for schizophrenia or other psychiatric conditions.”

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