Drinking leaves a mark
New biomarkers of alcohol intake could help protect those most vulnerable to the hazards of drinking.
“Prenatal alcohol exposure is the leading preventable cause of developmental disorders in children in the world. However, FASD is globally underdiagnosed,” University Researcher Olli Kärkkäinen says.
FASD, short for foetal alcohol spectrum disorders, refers to the range of physical and mental defects caused by alcohol use during pregnancy. The prevention, diagnosis and treatment of FASD are challenged by the lack of reliable methods to detect alcohol use among expectant mothers.
“While many abstain from alcohol during pregnancy, those who do drink tend to underreport it. If alcohol use could be detected with a routine blood test, we could better identify mothers and babies at risk.”
Serum metabolite profiling could offer a tool for the purpose, since alcohol use alters several metabolic functions. Kärkkäinen and colleagues have shown that serum metabolic profiles of alcohol-using pregnant mothers differ from those of controls. Mass spectrometry-based, non-targeted metabolic profiling of serum collected during the first trimester of pregnancy revealed several alcohol use-related changes among mothers who fit the criteria of harmful alcohol consumption.
“The risk profile included increased levels of glutamate and decreased levels of glutamine, which may reflect dysfunctional glutamate metabolism. Glutamate is a major neurotransmitter and is also involved in brain development.”
In addition, alcohol users had lower levels of serotonin, a transmitter with many functions in the body.
Next, a larger number of samples will be analysed from the Kuopio Birth Cohort study.
“Now we want to study if we can actually detect alcohol use based on the metabolomic profiles and also among mothers who said they used alcohol only moderately or very little.”
Kärkkäinen points out that there is no known safe level of alcohol use during pregnancy. What’s more, similar alcohol exposure can lead to varying degrees of damage in different pregnancies. Among other things, genes and diet can affect the outcome.
”We will also analyse placenta samples and hope to identify critical molecular pathways altered by alcohol. With a better understanding of the pathological processes, maybe new ways could be found to support the development of children who have been exposed.”
Another concern is adolescent alcohol use, which was recently associated with changes in the metabolite profile in the Adolescents and Alcohol study. Especially among young women who drink heavily, increased concentrations of 1-metylhistamine correlated with reduced brain grey-matter volume. 1-methylhistamine is formed in the brain from histamine, the release of which is part of the inflammatory response that presumably plays a role in alcohol-induced brain damage.
“It is worth noting that these adverse changes were observed, although even the heaviest drinkers used socially acceptable amounts of alcohol.”
At the moment, Kärkkäinen is also applying metabolomic analysis to post-mortem brain samples from alcoholics in the Tampere Sudden Death study. Another project carried out with Dr Lorenzo Leggio of the US National Institutes of Health focuses on metabolite changes after acute alcohol consumption. Besides academic research, Kärkkäinen is one of the founders of Afekta, a company offering comprehensive metabolomic services.
In 2018, he received the ESBRA Nordmann Award, which is presented every two years to a young scientist for significant contributions to biomedical research on alcohol dependence.