For the past three years, I’ve been working with kids and teens around the country, especially groups of girls. During my talks at schools, I’ve been asking girls to write down things they wish they could tell the adults in their lives but can’t seem to voice. What they’ve revealed worries me, and it should worry you, too. “I wish they knew how scared I am to grow up and how scared I am of the world,” reads a typical message. “I wish they knew ‘I’m fine’ means ‘I’m not okay.’” “I feel like my whole life is made of mistakes.” “Ninety percent of the time I smile, but I’m not happy.”

Why Do Teenage Girls Feel So Sad?

These anecdotal admissions echo the research which has permeated recent headlines. Emergency room visits for mental health concerns among boys have gone down since the pandemic, but have remained high among girls. Girls “persistently feeling sad and hopeless” seems to be our new normal.

While much of the public conversation focuses on social media, peer pressure, and cultural expectations, there’s another part of the story we don’t talk about nearly enough: biology. Puberty brings profound changes to the brain and body as hormones set in. For girls, these changes can make them more vulnerable to unrelenting emotional distress. Understanding the biology behind girls’ mental health is essential if we want to help them thrive.

Persistent stress has serious consequences for mental and physical health, something neuroscientists have known for a long time — and a topic that is the source of my book, Girls on the Brink. But until recently, their research on stress focused on males. Why? Researchers wanted to keep those pesky hormones from messing up their studies. Now, however, after decades of neglect, scientists are unpacking the distinct ways in which chronic stress affects female biology, especially at puberty.

One clue that has long indicated that stress affects girls in unique ways is the fact that sex differences in mental and physical health start to appear after puberty. For decades, we didn’t really understand why we saw such stark differences in rates of depression and disorders like autoimmune disease between girls and boys after the onset of puberty.

How Stress Affects Girls vs Boys

Chronic stress can affect the developing male and female brain in different ways. What researchers have found can help us, I think, to better support and help our girls.

Here’s what we know: Immunologists who study sex differences have shown that when girls’ stress levels rise, estrogen hormones boost the inflammatory stress chemicals of the immune system, ostensibly to afford greater protection for bearing children. But when stress levels stay elevated, this heightened stress response can get stuck in overdrive. That’s problematic because an over-exuberant inflammatory stress response can trigger immune cells that reside in the brain — called microglia — to become overactive and overprune synaptic connections in unhealthy ways. Over time, this can show up as depression and anxiety.

This has huge consequences for how the brain develops at puberty. Imagine that the female brain is a house, that estrogen-driven puberty is a period of major remodeling and rebuilding, and that external stressors are a sweeping thunderstorm. Imagine you’ve lived in the same house for a while, and you’re about to undergo a renovation. You decide to redo the interior walls, the electrical wiring, and basic plumbing. Suddenly, a big thunderstorm sweeps through the area, flooding the house. As you begin to remodel after the storm has passed, the pipes, electrical system, floors, and interior will have sustained some lingering damage.

Puberty is the stormy period during which past and present environmental insults begin to manifest in the remodeling changes made to the architecture of the brain.

Then, based on the information the brain and body have absorbed, the brain that was once so wide open and loosey-­goosey during puberty begins to tighten up again. It’s a different brain, based on whatever big, lasting environmental stressors it has faced along the way.

Too Much Too Soon

Girls are especially vulnerable to this neural remodeling during puberty when estrogen levels surge — because estrogen ramps up the stress-immune response. So it’s concerning to scientists that girls today are hitting puberty earlier than in the past. Breast buds — the first sign of puberty — appear in many girls by age 9, and girls are having their first periods, on average, at 12. (Six generations ago, girls had their first periods at age 16.)

Girls are also entering puberty before their brains have learned how to navigate social and emotional distress. And this is a problem. Why? With earlier puberty, the parts of the brain that put emotional stress in context or discern how to ask for help from adults haven’t wired and fired up yet. This makes it harder for them to know if something stressing them out is huge or small, how to voice their feelings, and how to ask for help. This means girls are facing intense emotional stress at a time when their brains are still developing the neural networks needed to manage it. Add to that their bodies’ stronger and longer-lasting release of inflammatory stress chemicals, and the result is a perfect storm for developing mood disorders like depression.

In my work with teen girls, I’ve heard story after story of quiet suffering. Girls feel overwhelmed, anxious, and unsure where to turn. Their experiences aren’t isolated; they reflect a growing body of research showing that adolescent girls are more vulnerable to mental health challenges than boys, and that persistent stress affects them differently, both psychologically and biologically. The more we understand the science behind these differences, the better we can support our children with compassion and clarity. But to do that, we must also confront the gaps in our knowledge. For too long, medical and psychological research has focused more on boys, leaving critical questions about girls’ development unanswered. Raising awareness about these disparities is a crucial step toward helping parents help their daughters not just survive adolescence, but thrive.