A new in vivo study has linked schizophrenia with an overload of a common amino acid in pregnant mothers. The researchers hope that their findings could lead to novel treatments and a better model of the disorder.
“Positive symptoms” refer to those that are typical to people diagnosed with schizophrenia, and which do not occur in healthy people. These may include hallucinations, delusions, and disturbed thoughts.
“Negative symptoms,” by contrast, are disruptions of normal behaviors, such as an apparently emotionless demeanor (known as “flat affect”), no longer taking pleasure in hitherto pleasant activities, or experiencing difficulties in carrying on various activities.
According to the National Institute of Mental Health, risk factors for schizophrenia range from genetic and environmental factors to chemical imbalances in the brain.
Currently, treatments for schizophrenia include antipsychotic drugs, psychosocial treatments (teaching people diagnosed with the disorder how to cope in a social environment), and a more complex approach called “coordinated specialty care,” which involves both drug prescriptions and a varied range of therapies focused on coping and integration.
A new study conducted by researchers from the University of California, Irvine has now uncovered another possible cause of the disorder, offering fresh hope for developing more effective treatments and preventive approaches.
The study focused on the role of excess methionine in the bodies of pregnant mothers. Methionine is an amino acid that cannot be synthesized by the body, and yet is crucial to the process of DNA methylation, which is a mechanism that drives gene expression.
The study concluded that excess methionine in the mother’s system can lead to a faulty development of the fetus’s brain, which can lead, in turn, to onset schizophrenia.
As Dr. Alachkar explained for Medical News Today, “Methionine is central to the one-carbon metabolism. It is the amino acid that regulates methylation. We have […] learned that schizophrenia is a multigenic, developmental, and epigenetic disorder. Methylation is fundamental to all these processes.”
Dr. Alachkar and her colleagues’ research was spurred by
“We realized that older studies had shown that administration of methionine exacerbates the schizophrenic symptoms,” Dr. Alachkar explained. This led the researchers to conduct their own in vivo experiments, which revealed that methionine intake caused schizophrenia-like behavioral deficits in adult mice.
Excess methionine linked with schizophrenia
However, she declared that these effects “were found to be transient.” To test the consistency of their hypothesis, the researchers designed the current study, in which they experimented with methionine on “pregnant mice during the third week of pregnancy at the time of brain development,” Dr. Alachkar told us.
The researchers administered three times the normal daily dose of methionine to the mice, keeping the same ratio that the older studies had employed. This was to test the hypothesis that pregnant mice receiving excess methionine would produce offspring with schizophrenia-like deficits.
The pups did exhibit developmental deficits consistent with schizophrenia as confirmed by nine different tests, which were centered both on positive and negative symptoms, as well as on cognitive impairments such as memory loss.
When the researchers administered antipsychotic drugs used in schizophrenia treatments to these mice, they noticed that they were effective. The mice were given haloperidol, which is a drug that targets positive symptoms, and clozapine, which mostly targets negative symptoms and cognitive impairments.
Genetic implications for schizophrenia
Dr. Alachkar told MNT that the study held several surprises, potentially leading to a fresh perspective on schizophrenia. Their most significant findings, she said, were that “the mice displayed the symptoms that last permanently as in schizophrenia, [and that] the antipsychotic drugs display [a] reversal of the behavioral deficits that reflect[s] their therapeutic effects in human schizophrenics.”
More importantly, Dr. Alachkar pointed out that “one of the genes found to be downregulated in our animals, Npas4, has been associated with schizophrenia.” According to the researcher, this is the first time it has been shown “that in specific regions of human brains [this gene] is also downregulated.”
The team hopes that their research will allow for the development of a new mouse model in the study of schizophrenia – one that takes into account the impact of “the prenatal methionine treatment,” and that “carries the multigenic, developmental, and epigenetic aspects” of the disorder, as Dr. Alachkar put it.
In the future, the researchers are interested in looking at schizophrenia mechanisms from a molecular perspective, and in seeing whether novel treatments could be devised.
“We now want to study the molecular basis for the behavioral deficits to find new therapeutic targets. We also would like [to] extend our studies on the reversal of the behavioral deficits to novel antipsychotic drugs as well as compounds that regulate the one-carbon metabolism as potential new antipsychotics.”
Dr. Amal Alachkar