The role of inflammation and the immune system in adolescent depression |

Dr. Valentina Zonca, from the Department of Pharmacology and Biomolecular Sciences at the University of Milan, shares with us the latest findings on the role of inflammation in depression from the MQ-funded IDEA RiSCo study, in this Recently published article.

Depression is becoming increasingly common among adolescents, so it is crucial to understand the biological causes of this condition to develop new and better prevention and treatment strategies.

Most research investigating the biological mechanisms underlying depression has focused on adults, mainly in wealthy countries, with few studies focusing on adolescents and even fewer considering environmental risk factors. Although around 90% of the world’s adolescents live in low- and middle-income countries, most research has been conducted in high-income countries, such as Europe and the United States.

The different challenges faced by adolescents in low- and middle-income countries, such as poverty, high crime rates, and school dropouts, could play an important role in the onset of depression.

Therefore, understanding these mechanisms is crucial to have a global perspective on adolescent depression. Taking into account these premises, in the context of the IDEA (Identifying Depression Early in Adolescence) project, this study aims to identify the biological characteristics underlying adolescent depression by focusing on adolescents from a middle-income country, specifically Brazil, and using a unique risk score to classify adolescents at different levels of risk for future depression, and not just based on whether they currently have the disorder.

We analyzed blood samples to identify biological factors associated with depression and its risk factors. Specifically, we collected blood samples from 150 Brazilian adolescents between 14 and 16 years old, and this group included 50 adolescents diagnosed with depression, 50 adolescents classified as being at high risk of developing depression according to the risk score mentioned above and developed by other members of the IDEA Team, and 50 at low risk of developing depression.

To understand what is happening at a biological level, we analyze blood samples to observe the gene expression of adolescents, using cutting-edge techniques such as RNA sequencing. Gene expression is the process by which our cells use the instructions from our genes to produce proteins, which in turn regulate the functioning of our body. Analysis of gene expression can give us an idea of ​​whether and/or how our biological systems are affected under certain conditions.

In our study, we found that adolescents with depression have a higher activation of biological pathways related to inflammation and activation of the immune system, which is the main system that protects us from infections. Interestingly, these inflammation-related pathways were more pronounced in girls with depression compared to boys. This represents a very interesting result, as it helps us better understand the possible biological differences in what could cause depression in girls and boys; clarifying this is particularly important when we consider that the incidence of depression is twice as high in female adolescents compared to boys.

In conclusion, we found that inflammation and immune-related pathways play an important role in adolescent depression, and showed that these pathways were more active in adolescents with depression compared to those without, regardless of their level of risk for developing depression.

This finding is illuminating, as it suggests that increased inflammation could be a biological mechanism involved in the onset of adolescent depression, especially in girls. Better investigation of these biological mechanisms could help to understand why depression affects adolescents differently depending on their biological sex, as well as to implement new prevention strategies to act promptly and prevent the onset of depression in adolescence.

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