Teen depression and the immune system: do patterns differ in boys and girls?

Researchers found that immune system changes are associated with depression in teenagers and these changes show up differently in boys and girls.

Depression is a mental health condition that makes people feel sad, hopeless, numb, and lose interest in activities they once enjoyed. It often begins during adolescence, a time when the brain and body are still growing and changing. Because of this, scientists want to understand what is happening inside the body when depression first starts.

One area that researchers explored in relation to depression is the immune system, which is the body’s natural defence against illness. When the immune system is “in defence mode”, it releases small messenger proteins called cytokines. These cytokines act as inflammatory markers, meaning they can give us clues that inflammation is happening in the body. They also act like signals, telling different parts of the body how to respond to infection, injury or stress. Psychological stress can also activate these signals, which is important as stress is not only something people feel emotionally but something that can affect the body as well, especially when it is repeated and long-lasting.

While inflammation is helpful when the body is fighting sickness, too much of it, or inflammation that lasts too long can affect the brain and mood. Scientists are still learning how these messages from the immune system are linked to depression in teenagers, and whether they affect boys and girls in different ways.

To explore this idea, researchers from King’s College London and Brazil’s Universidade Federal do Rio Grande do Sul carried out a study as part of the IDEA project (Identifying Depression Early in Adolescence). Their goal was to understand whether specific inflammatory markers were linked to both increased risk of developing depression and the presence of depression in teenagers, and whether these links were different for boys and girls.
The study included 150 adolescents aged 14 to 16 who were divided into three equal groups using a screening tool called the IDEA Risk Score (IDEA-RS). The IDEA-RS was developed by the team to help detect risk of depression in adolescents and it is based on 11 social and life factors, some of which include early life stress, experiences of abuse or neglect in childhood, running away from home, involvement in fights, relationships with parents, and drug use. Based on IDEA-RS and the depression scores, adolescents were divided into 3 groups: 50 teens who were at low-risk for depression, 50 who were at high-risk, and 50 who were diagnosed with major depressive disorder. Each group included the same number of boys and girls.

To find answers, researchers collected blood samples from teenagers and used advanced laboratory equipment to measure levels of cytokines (the immune system messengers). The researchers then used statistical tools to compare cytokine levels between teens at low-risk for depression, those at high-risk, and those who were already depressed, and to explore whether patterns differed in boys and girls. These tools helped them determine whether the observed differences were meaningful and truly linked to depressive symptoms, rather than simply due to chance. The researchers found that different immune markers were linked to depression in boys and girls.

In boys, levels of the cytokine Interleukin-2 (IL-2) increased as the risk of depression increased and were highest in those who were already depressed. Higher IL-2 levels in boys were also linked to more severe depressive symptoms. IL-2 helps regulate how immune cells grow and work, supporting the body’s ability to defend itself. In girls, a different cytokine, IL-6, was linked to how severe their symptoms were, but not to risk level. IL-6 plays a role in inflammation, which is the body’s natural defence response to fight sickness or injury. Overall, this suggests that the immune system may be involved in depression in different ways for boys and girls.

These findings help explain why depression may not look the same in all teenagers. The study suggests that boys and girls may follow different biological pathways as depression develops. This means that stress and immune activity might affect their brains and emotions in different ways. Understanding these differences could help doctors better recognize early warning signs and design treatments that are more tailored to each person. The results also highlight that depression is not only about thoughts and feelings but that it is closely connected to what happens in the body.

This study also shows both what scientists have learned and what still needs to be explored. The researchers measured chemicals in the blood, not directly in the brain, so they cannot be completely sure how closely these levels reflect what is happening inside the brain. The study also took place at one point in time, which means it cannot tell whether the immune changes cause depression or are a result of it. When the data were divided by sex, the smaller group sizes made some results harder to interpret with confidence. Whilst conducting the study in Brazil was one of the strengths due to limited research in the low-and-middle income settings, more research is needed to see if the same patterns appear in other countries and cultures.

Despite these limitations, the findings offer hope. Importantly, the study used the IDEA-RS to group adolescents based on their risk, which is a novel approach that captures a range of vulnerability rather than simply comparing depressed and non-depressed. Because the IDEA-RS combines multiple social and life factors, it may be useful as a future screening tool to identify adolescents at higher risk of depression, an approach reflected in the study design, which included adolescents at low risk, high risk, and with a diagnosis of depression to enable comparison across groups. It also used a broad range of social and life factors to identify risk, included equal numbers of boys and girls, and focused on adolescence as a key period for understanding the development of depression. In addition, the researchers measured several immune markers using established laboratory methods, which strengthens the reliability of the findings.

These findings suggest that scientists are getting closer to understanding how depression may develop during adolescence and why it may affect boys and girls differently. This growing knowledge could one day help guide better prevention strategies, earlier detection, and more personalized approaches to treatment. By recognizing that depression involves both the mind and the body, researchers and doctors can continue working toward more effective ways of supporting young people and helping them build healthier futures.

This research was part of the IDEA project (Identifying Depression Early in Adolescence) an international research collaboration investigating how depression develops during the teenage years. The work was supported by a combination of mental health charities and public research funders in the UK and Brazil, including organisations that support global mental health research. The scientists thanked the participating young people, families, schools, and the research team as their work brings us closer to unlocking the how depression works in the body and mind of adolescents.

No conflict of interest was stated by the research team.