Health

Biological pathways in the brain help explain why teenage girls are depressed than boys

Depression is a mental health condition that affects 280 million people around the world. It is twice as common in women than in men, and this pattern begins to develop during puberty. Researchers have studied biological processes that promote depression in adults and demonstrated a potential role for the kynurenine pathway, the first time that has been investigated in adolescents in relation to biological sex.

This study was published in Biological psychiatry Funded by MQ Mental Health Research and supported by the National Institute of Health Therapy (NIHR) Maudsley Biomedical Research Center (BRC).

The kynurenine pathway is a series of chemical reactions that treat tryptophan, an amino acid found in foods. When tryptophan is broken down, it can take two pathways in the brain. One produces neuroprotective (cerebral protection) chemicals, and the other produces neurotoxic (cerebral damage) chemicals. This process involves several by-products, including kynurenic acid (neuroprotection) and quinophosphate (neurotoxicity).

Professor Valeria Mondeli, senior author of IOPPN, a clinical professor of psycho-immunology at King and the theme lead of mood disorders and psychosis at NIHR Maudsley BRC, said, “Adolescents are a time when many changes occur in the brain and body, but there is little to know about the potential depression, and the difference in this study. The development of depression during teenagers may help us understand why there is a higher incidence during adolescence.

Using blood tests, this study assessed kynurenic acid and quinophosphate levels in a group of 150 teenagers from Brazil between the ages of 14 and 16. Teens belonged to one of three groups: those at a low risk of depression, those at a high risk of depression, and those diagnosed with depression. Risks were assessed using scales developed as part of the identification of early adolescence (IDEA) projects, taking into account a variety of factors¹. Each group had 50 adolescents, and were evenly divided by biological sex to explore differences between male and female adolescents. Adolescents were followed for three years to assess whether the adolescent's symptoms persisted or improved.

Researchers at King's College London found that adolescents at high risk of depression or who have been diagnosed with depression had lower levels of the neuroprotective compound, kynurenic acid. This reduction is most evident in female adolescents, suggesting that girls may be more vulnerable to the harmful effects of the disproportionate kynurenine pathway in adolescence, potentially explaining why women experience depression at a higher rate.

This study also measured certain proteins in the blood that indicate that the body is in an inflammatory state and is released during infection, stress or illness. We found that higher levels of these inflammatory markers are associated with increased production of neurotoxic chemicals in the kynurenine pathway. In particular, this association was found in high-risk or depression adolescents, but not in low-risk adolescents. This suggests that inflammation may drive the kynurenine pathway towards the production of neurotoxic chemicals, increasing the risk of depression.

Follow-up 3 years later showed that female adolescents with persistent depression had higher levels of neurotoxic metabolites than patients who recovered over time, suggesting that increased neurotoxic activity in the kynurenine pathway could make depression difficult for some adolescents.

The first author and senior researcher of IOPPN Naghmeh Nikkheslat, King, said, “Our research shows that measurement of chemicals involved in the kynurenine pathway may help identify people at risk for persistent depression, especially among women, particularly among women. The pathway from medication to lifestyle changes such as diet and exercise.”

Sources

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2/ https://www.sciencedaily.com/releases/2025/03/250325115846.htm

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