In the great nature vs. nurture debate, nature just got a win. UCI research led by Amal Alachkar found that too much of a certain amino acid in utero caused schizophrenia in mice despite the quality of postpartum caregiving — and the study suggests that the same would be true with humans.
The team plans to use the findings to develop better treatments for — and possibly avert — schizophrenia and other psychiatric disorders. Alachkar, associate professor of teaching in pharmaceutical sciences, said:
“My principle is to not wait until you see the symptoms. The roots of the symptoms are very, very early, so why don’t we do something to prevent rather than to intervene?”
The nature of schizophrenia
The study, published in Communications Biology, is the most recent of three showing how mice that receive extra methionine, an amino acid essential to metabolism, experience genetic and behavioral changes that mark schizophrenia in humans. The first found that giving extra methionine to adult mice caused them to exhibit symptoms of schizophrenia, such as social withdrawal and impaired communication, memory, and reasoning skills.
The second demonstrated that mice that received excess methionine during the brain development stage of pregnancy had offspring whose genes and behavior indicate schizophrenia in people. These studies led Alachkar to ask: Were schizophrenic mother mice inducing symptoms in their children, or were these symptoms purely natural? She said:
“We know that caregiving in the early stage of life can be very important for psychiatric disorders.”
The third study answers the question. The researchers switched the offspring at birth so that the pups with extra methionine were fostered by mothers without it and vice versa. It made no difference: The pups with excess methionine showed signs of schizophrenia, and those without it did not. Nurture was unable to rescue the former from developing schizophrenic behaviors. Nor did it engender the disorder in offspring without the extra amino acid. Alachkar said:
“That means there are changes that occur very early in life, before nurture can have any effect.”
Working with UCI’s Geoffrey Abbott, professor of physiology & biophysics, and Pierre Baldi, Distinguished Professor of computer science, the team analyzed the pups’ brain chemistry, genes, and activity. They found that about 800 genes were affected by the excess methionine and that within 24 hours of birth, these genes had altered the pups’ brains.
The results match schizophrenia in humans, and the researchers are confident that the changes the mice experienced would occur in people as well. Because they were able to detect the differences so early in life, scientists believe that a drug could be developed to stop these changes from happening. Abbott said:
“This could point the way to biomarkers or even potential therapies for schizophrenia.”
Other applications
The goal is to create pharmaceuticals to treat, cure, or — ideally — prevent schizophrenia. Currently, medications can only address a few symptoms, such as hallucinations. Alachkar said:
“But what’s disabling in schizophrenia patients are the cognitive dysfunctions that make them really withdrawn from life, unable to even have employment. If we were able to develop a better treatment, those patients would be able to work, to communicate with others, to live a normal life.”
And schizophrenia patients may not be the only ones to benefit. One gene that showed a particularly large change is already associated with epilepsy, autism, and Alzheimer’s, “suggesting at least one common thread between these diseases and schizophrenia,” Abbott notes. Alachkar added:
“There are a lot of overlapping symptoms between schizophrenia and autism and between schizophrenia and Alzheimer’s. So I started to think, ‘Are we seeing the same mechanisms that start very, very early in life?’”
She wonders whether autism, schizophrenia, and Alzheimer’s are actually the same disease presenting themselves differently in childhood, adolescence, and old age, respectively. Alachkar said:
“I’m very interested now in collaborating to see if we can use these pathways as targets for therapies not only for schizophrenia, but also for autism and Alzheimer’s.”
Provided by: Nicole Feldman, University of California [Note: Materials may be edited for content and length.]
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