Brain Pathway Discovery Sheds Light on Higher Depression Rates in Teenage Girls
Depression is a mental health condition that affects 280 million people worldwide. It is twice as common in women than men and this pattern starts to develop during adolescence. Researchers have studied the biological processes that drive depression in adults and shown a potential role for the kynurenine pathway, but this is the first time it has been investigated in adolescents in relation to biological sex.
The study was published in Biological Psychiatry
Using blood tests, the study assessed the levels of kynurenic and quinolinic acids in a group of 150 teenagers from Brazil aged between 14 and 16. The teenagers belonged to one of three groups - those with low risk of depression, those with high risk of depression and those who had been diagnosed with depression. Risk was assessed using a measure that had been developed as part of the Identifying Depression Early in Adolescence (IDEA) project and considers a range of factors1. There were 50 adolescents in each group and they were evenly divided by biological sex to explore differences between male and female adolescents. The adolescents were tracked over three years to assess if their depression symptoms persisted or improved.
The study also measured specific proteins in the blood that indicate the body is in an inflammatory state, and are released during infection, stress, or illness. It found that higher levels of these inflammatory markers were linked to increased production of neurotoxic chemicals in the kynurenine pathway. Notably, this association was found in adolescents at high-risk or with depression, but not in low-risk adolescents. This suggests that inflammation might drive the kynurenine pathway toward producing neurotoxic chemicals, increasing the risk of depression.
In the follow-up three years later, the study showed that female adolescents with persistent depression had higher levels of neurotoxic metabolites than those who recovered over time, suggesting that increased neurotoxic activity in the kynurenine pathway could make depression harder to overcome for some adolescents
Ref: Nikkheslat, N. et al. Sex-Specific Alternations of Kyneurenine Pathway in Association with Risk and Remission of Depression in Adolescence.Biological Psychiatry https://doi.org/10.1016/j.biopsych.2024.11.020
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