Why teen girls struggle more with depression

In every classroom, on every street, there are teenagers quietly battling depression. It’s a growing crisis, one that does not treat everyone equally. Around the world, depression strikes women twice as often as men.

This disparity begins not in adulthood but during adolescence. While hormones, social pressure, and life events all play roles, new science is pointing to something deeper – something biological.

A new study published in Biological Psychiatry explores how brain chemistry may drive this gender divide. It focuses on a lesser-known series of chemical reactions in the brain called the “kynurenine pathway.”

This pathway has long been studied in adults with depression, but for the first time, scientists have turned their attention to teenagers. The goal was to find out whether differences in this brain chemistry could explain why depression takes root more strongly in adolescent girls.

Biological drivers for depression

Tryptophan breaks into two key products. Kynurenic acid protects the brain. Quinolinic acid harms it. These chemicals may influence how depression develops.

The researchers focused on this pathway in teenagers, examining how these brain chemicals differ between boys and girls.​

“Adolescence is a time when many changes occur in the brain and body but we still know very little about the possible biological drivers for depression and how this might affect the difference between teenage boys and girls,“ said Professor Valeria Mondelli from King’s IoPPN.

“Our study indicates the ‘kynurenine pathway’ plays a role in development of depression during the teenage years which may help us to understand why there is a higher incidence amongst girls.”

“During adolescence there are a wide range of social and individual factors that influence mental health and by identifying the biological pathways involved we hope we can help build a clearer picture of how we can help teenagers manage depression.”

Teen girls with a chemical imbalance

The teenagers, aged between 14 and 16, were placed into three distinct groups based on their mental health profiles: those with low risk of depression, those considered high risk, and those already diagnosed with depression.

Each group included 50 adolescents, with an equal number of boys and girls. To determine risk levels, the researchers used an assessment developed as part of the IDEA project, which evaluates various psychological and social factors.

The participants were then tracked over a period of three years to observe whether their symptoms improved or remained.

The findings revealed that teens with a high risk of depression or a current diagnosis had lower levels of kynurenic acid, a chemical known to protect the brain.

This decrease was especially evident among girls, suggesting that an imbalance in the kynurenine pathway may affect them more severely during adolescence.

Inflammation and its role in depression

The experts also measured proteins that show inflammation. These markers rise during infection or stress.

The researchers found high inflammation levels linked to more quinolinic acid. This means inflammation could push the kynurenine pathway toward damage.

This pattern appeared only in high-risk or depressed teens. Low-risk teens did not show the same chemical changes. That points to inflammation as a driver of depression’s deeper roots in the brain.

Persistent depression in teen girls

Three years later, the researchers checked back in. Girls with ongoing depression had more neurotoxic chemicals in their blood. Those who improved had lower levels, suggesting that a long-term chemical imbalance might slow recovery.

“Our study indicates that the measurement of chemicals involved in the kynurenine pathway could potentially help identify those who at risk of persistent depression, particularly amongst females, as well as inform the approaches we take to providing support,“ said Dr. Naghmeh Nikkheslat, the study’s first author.

“This insight could help develop more targeted support for teenagers with depression through interventions that work in a range of ways on the kynurenine pathway from medication to lifestyle changes such as diet and exercise.”

Personalized support is needed

This research could change how we detect and treat teen depression. Measuring brain-related chemicals may help flag those most at risk. With more data, doctors might offer depression support earlier, especially to girls.

By linking biology to mental health, the study brings new options to the table. It offers hope for more effective, personal care in the teenage years.

Funded by MQ Mental Health Research, the research received support from the NIHR Maudsley Biomedical Research Centre. 

The study is published in the journal Biological Psychiatry.

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