Researchers at the Centre for Addiction and Mental Health (CAMH) in Canada have been studying the genetic underpinnings of lactose intolerance in order to gain a better understanding of the origins of certain severe mental disorders, such as schizophrenia.
Although lactose intolerance and schizophrenia appear to have very little in common, the researchers explain two major similarities: First, both conditions are passed down genetically. And secondly, their symptoms never emerge during the first year of life, and in most cases, don’t appear until decades later.
This slow development can be explained by a combination of genetics and epigenetics –factors that turn genes on or off, say the researchers. By studying the basic principles behind lactose intolerance, they can then be applied to the study of more complex mental illnesses such as schizophrenia, bipolar disorder, or Alzheimer’s disease.
All of these conditions feature DNA risk factors but take decades before clinical symptoms develop, said senior author Dr. Arturas Petronis, head of the Krembil Family Epigenetics Laboratory in the Campbell Family Mental Health Research Institute at CAMH.
More than 65 percent of adults worldwide are lactose intolerant, meaning they cannot process the milk sugar lactose. Lactose intolerance is influenced by a single gene, which determines whether an individual will lose the ability to process lactose over time. People with variants of this gene will gradually produce less lactase, the enzyme that breaks down lactose, as they age.
“The question we asked is why does this change happen over time? All newborns are able to digest lactose, independently from their genetic variation,” said Petronis. “Now, we know that epigenetic factors accumulate at a very different pace in each person, depending on the genetic variants of the lactase gene.”
Over time, these epigenetic changes build up and inactivate the lactase gene in some, but not all, individuals. At this point, people with the inactivated lactase gene would start noticing new symptoms of lactose intolerance.
Mental illnesses are far more complex than lactose intolerance and are linked to many more genes with their epigenetic surroundings. Even so, the same molecular mechanisms may account for the delayed age of onset of illnesses, such as schizophrenia, in early adulthood, Petronis said.
The combination of genes and epigenetic factors that build up over time with age, provide a likely avenue to investigate in illnesses such as schizophrenia.
“We came up with interesting hypotheses, and possibly insights, into risk factors for brain disease by studying aging intestines,” says Petronis.
Exploring the epigenetic control of the lactase gene involved a collaborative effort of CAMH, University of Toronto, the Hospital for Sick Children, Vilnius University, and the Lithuanian University of Health Sciences.
Their findings are published in the journal Nature Structural and Molecular Biology.