Brain Pathway May Explain Higher Depression Rates in Teen Girls

Depression affects 280 million people globally and is twice as prevalent in women as in men, a trend that emerges during adolescence. While researchers have linked the kynurenine pathway to depression in adults, this study is the first to examine its role in adolescents based on biological sex.

The study, “Sex-Specific Alterations of the Kynurenine Pathway in Association with Risk and Remission of Depression in Adolescence,” was published in Biological Psychiatry.

The kynurenine pathway is a series of chemical reactions that break down tryptophan, an amino acid found in food. When processed in the brain, tryptophan can follow two pathways: one producing neuroprotective compounds and another generating neurotoxic ones. Key byproducts of this process include kynurenic acid, which supports brain health, and quinolinic acid, which can be harmful.

Understanding Biological Factors in Adolescent Depression

Professor Valeria Mondelli, senior author and Clinical Professor of Psychoneuroimmunology at King’s IoPPN, emphasized the significance of adolescence as a period of major brain and body changes. However, she noted that little is known about the biological factors contributing to depression and the differences between teenage boys and girls.

“Our study suggests the kynurenine pathway plays a role in the onset of depression during adolescence, potentially explaining the higher prevalence among girls,” Mondelli said. “Since mental health is shaped by various social and individual factors during this time, identifying the biological mechanisms involved could provide a clearer understanding of how to support teenagers struggling with depression.”

The study used blood tests to measure levels of kynurenic and quinolinic acids in 150 Brazilian teenagers aged 14 to 16. Participants were divided into three groups: those at low risk for depression, those at high risk, and those already diagnosed with depression.

Tracking Depression Risk and Gender Differences in Adolescents

Depression risk was assessed using a method developed as part of the Identifying Depression Early in Adolescence (IDEA) project, which considers multiple factors. Each group included 50 adolescents, evenly split by biological sex, allowing researchers to analyze differences between males and females. The participants were tracked over three years to monitor changes in their depression symptoms.

Researchers at King’s College London found that adolescents with a high risk of depression or a current diagnosis had lower levels of kynurenic acid, a neuroprotective compound. This reduction was more pronounced in female adolescents, suggesting that an imbalanced kynurenine pathway may make girls more vulnerable to depression, potentially explaining why they experience the condition at higher rates.

Inflammation’s Role in Depression and the Kynurenine Pathway

The study also measured blood proteins linked to inflammation, which the body releases during stress, illness, or infection. Findings showed that elevated levels of these inflammatory markers were associated with increased production of neurotoxic chemicals in the kynurenine pathway. This pattern was observed in high-risk and depressed adolescents but not in those at low risk.

These results suggest that inflammation may push the kynurenine pathway toward producing harmful neurotoxic compounds, increasing the likelihood of depression.

In a follow-up three years later, researchers found that female adolescents with persistent depression had higher levels of neurotoxic metabolites than those who recovered, indicating that heightened neurotoxic activity in the kynurenine pathway may make depression more difficult to overcome.

Dr. Naghmeh Nikkheslat, first author and Senior Research Associate at King’s IoPPN, highlighted the potential clinical relevance of these findings.

“Our study suggests that measuring kynurenine pathway chemicals could help identify individuals at risk of persistent depression, especially females, and guide more effective support strategies,” she said. “This insight could pave the way for targeted interventions, from medication to lifestyle changes such as diet and exercise.”

Read the original article on: Medical X Spress

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