AsianScientist (Jul. 29, 2019) – In a study published in EBioMedicine, researchers in Japan have shown that supplementing mice with betaine can counteract psychiatric symptoms.
Many psychiatric drugs act on the receptors or transporters of certain neurotransmitters in the brain. However, there is a great need for alternatives, and scientists are looking at other targets along the brain’s metabolic pathways. A lack of betaine contributes to brain pathology in schizophrenia, and new research from the RIKEN Center for Brain Science, Japan, shows that betaine supplementation can counteract psychiatric symptoms in mice.
Betaine comes from a normal diet but is also synthesized in the body where it contributes to metabolism in various ways, including as an anti-inflammatory agent. In this study, mice missing the Chdh gene, which is involved in making betaine, showed depressive behaviors and greatly reduced betaine levels in both the brain and blood as compared to normal controls. Betaine levels in the brain recovered when Chdh-null mice received the compound as a supplement in drinking water, demonstrating that betaine can pass through the blood-brain barrier.
Psychedelic drugs like phencyclidine (PCP) and methamphetamine can also produce schizophrenia-like behaviors in both humans and mice. The researchers thus tested whether betaine supplementation could help alleviate symptoms induced by PCP and methamphetamine in mice. They found that betaine not only limited the extent of cognitive deficits and behavioral abnormalities, it also reversed oxidative stress at the molecular level. Oxidative stress is thought to be one mechanism by which these drugs cause psychiatric symptoms in humans.
Finally, investigation of post-mortem human brain samples did indeed show reduced betaine levels in patients with schizophrenia, which was unrelated to the amount of antipsychotic drugs taken before death. The researchers also found a subset of brain samples with ‘betaine-deficit oxidative stress,’ a pathology that occurred in patients with severe psychotic symptoms. The team was able to replicate this pathology in induced pluripotent stem cells under conditions of oxidative stress, then 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,” said senior author Professor Takeo Yoshikawa of RIKEN. “However, supplementation of betaine is not a silver bullet for schizophrenia or other psychiatric conditions.”
The researchers further identified a genetic variant that could predict the efficacy of betaine treatment, a potential example of precision medicine in psychiatry. Betaine is already used as a drug for the autosomal recessive metabolic disorder homocystinuria, so it could be considered as therapy for psychiatric conditions with minimal concern for adverse effects.
The article can be found at: Ohnishi et al. (2019) Investigation of Betaine as a Novel Psychotherapeutic for Schizophrenia.
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