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

Dr Valentina Zonca, from the Department of Pharmacology and Biomolecular Science at the University of Milan shares with us the most recent findings about the role of inflammation in depression from the MQ funded IDEA RiSCo study, in this recently published paper.


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

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

The different challenges faced by teenagers in the 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 for a global perspective on teenage depression. Given these premises, in the context of the IDEA (Identifying Depression Early in Adolescence) project, this study aims to identify the biological signatures underlying adolescent depression by focusing on teenagers from a middle-income country, specifically Brazil, and by using an unique risk score to classify adolescents into different risk levels for future depression, and not just based on whether they currently have the disorder.

We analysed blood samples to identify biological factors associated with depression and its risk factors. Specifically, we collected blood samples from 150 Brazilian teenagers aged 14-16, and this group included 50 adolescents with a diagnosis of depression, 50 teen-agers classified as having high risk of developing depression accordingly to the risk score previously mentioned and developed by other members of the IDEA Team, and 50 at low risk of developing depression.

To understand what is happening at biological level, we analysed blood samples to look at the adolescents’ gene expression, using state of the art technique like RNA sequencing. Gene expression is the process by which our cells use the instructions in our genes to make proteins, which in turn regulate the function of our body. Analysing gene expression can give us an idea of whether and how our biological systems are affected and/or try to respond in certain conditions.

In our study, we found that adolescents with depression present with increased activation of biological pathways related to inflammation and activation of the immune system, which is the main system protecting 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 to better understand possible biological differences in what could cause depression in girls and in boys; clarifying this is particularly important when we consider that the incidence of depression is double in adolescent females compared with males.

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

This finding is enlightening as it suggests that increased inflammation could be a biological mechanism involved in the onset of teenage depression, especially in girls. Better investing these biological mechanisms could help understanding why depression affects teenagers differently based on their biological sex, as well as implement novel prevention strategies to promptly act and prevent the onset of depression in adolescence.

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