Antidepressant medication affects brain lipid levels

Antidepressant medication affects brain lipid levels
Antidepressant medication affects brain lipid levels

Skoltech scientists and their colleagues from Russia, Germany and the United States conducted a study on monkeys, during which it was found that young macaques treated with the antidepressant Prozac for two years had lower brain lipids than controls. the drug was not received. Although none of the animals in the study group suffered from depression, these results suggest which biochemical processes in the brain may be responsible for the side effects of the drug in humans, especially at a young age.


The research results are published in the scientific edition of the International Journal of Molecular Sciences. Prozac is the most commonly prescribed antidepressant in the world. For example, in the United States, its use is approved even for the treatment of severe forms of depression in children from the age of eight, as well as obsessive-compulsive disorder from the age of seven.

However, some concerns remain about this practice: according to a number of studies, taking the drug may increase the risk of suicidal thoughts and behavior, and children and adolescents may be especially susceptible to this. In this regard, the study of the biochemical mechanisms of the effect of the main active substance of Prozac, fluoxetine, on the brain, especially in young patients, is of particular relevance.

Previously, another team of scientists working in collaboration with the authors of the article conducted a series of studies on the same group of animals, studying the effect of fluoxetine on impulsivity, sleep quality, social interaction and the level of metabolites in the blood of young monkeys who received Prozac for two years. In their new study, the authors of the article examined how fluoxetine affects gene expression and the content of metabolites, primarily lipids, in the brain of animals.

“The fact that lipids serve as a building material for cell membranes and store energy in adipose tissue of the body has been known for a long time, but the importance of lipids for the normal functioning of the brain has become evident quite recently. Lipids are present in the brain in huge quantities: they are not only the main component of the cell membranes of neurons, on which the properties of the membrane depend, but also form the basis of the myelin sheaths of axons. Surprisingly, the brain is almost 60 percent fat,”says Anna Tkacheva, the first author of the article, a researcher at the Skoltech Center for Neurobiology and Neurorehabilitation (CNBR).

Recent biochemical studies of the brain have established a link between the level of lipids in a person's blood and the course of diseases such as schizophrenia, depression and Alzheimer's disease. Thus, lipids can serve as an important marker of brain pathologies. In the course of the study presented in the article, only insignificant variations in gene expression and insignificant changes in the content of metabolites not associated with lipid metabolism were found.

On the other hand, postmortem analysis of the brain of macaques by mass spectrometry revealed a decrease in the concentration of a significant part of the more than 300 studied lipids: a reduced concentration was observed in lipids containing polyunsaturated fatty acids (PUFA) or representing free PUFAs occurring independently, and not in the composition of more complex lipid molecules.

It was in free PUFAs that the sharpest decrease in concentration was noted. Of all the PUFAs, the most widely known are omega-3 fatty acids, which are found in sea fish and some other foods.Their consumption has a positive effect on both physical and mental health of a person.

“It is known that the younger a child is, the faster natural changes occur in his brain. It is this fact that may be one of the reasons for the more pronounced manifestation of side effects of the antidepressant in children. During the first two years of life, the level of PUFA in the child's brain rises rapidly.

This is one of the reasons why breastfeeding is beneficial: breast milk is rich in fats and can provide the baby's brain with valuable building materials for lipid synthesis. Although the process of lipid accumulation in a child slows down over time, its final stage may also cover the early adolescence, which approximately corresponded to the age of the monkeys in our study,”notes Anna Tkacheva.

Investigating the content of metabolites in the blood of animals, scientists have identified a number of indirect signs indicating a decrease in the content of PUFA in the body as a whole, but the decrease was much more pronounced in the prelimbic cerebral cortex, the main object of the study. “The essential difference between the diets of humans and monkeys is that humans receive PUFAs from food, eating fish, meat and other PUFA-rich foods that are practically absent in the diet of monkeys - they have the entire load of producing these acids on the liver.

If in the course of further research it is confirmed that the imbalance in the lipid content we have identified is due precisely to the violation of the synthesis of these molecules, then we can talk about the possibility of reducing adverse side effects in patients by choosing the correct diet,”explains Tkacheva.

“This mechanism can be confirmed by examining human blood: since in macaques the imbalance in the level of brain lipids was reflected in the blood composition, we can hope to obtain similar results for humans, and no brain will need to be dissected,” Anna continues. - If the blood test does not show anything, this may indicate that the lipid imbalance is caused not by impaired synthesis, but by other factors. For example, the difficulty of penetrating lipids into the brain or their redistribution between brain regions. Such an alternative could be tested through research on animals like ours, but with an emphasis on other parts of the brain."

The study was conducted with the participation of specialists from the Skolkovo Institute of Science and Technology, Lomonosov Moscow State University, Max Planck Institute of Psychiatry, Ludwig Maximilian University of Munich (Germany) and University of California at Davis (USA).

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