The teen brain: How Mum´s behavior influences your resilience to stress

Adolescence is a time of rapid change and emotional challenges. It is also a critical period of brain development.

While it can be full of exciting experiences, it is marked by heightened sensitivity to stress and increased risk of mental health disorders.

Even though a staggering one-third of the world’s teenagers are at risk of depression, the neurological mechanisms underlying adolescent stress responses are still not fully understood.

But some young people seem to cope well with stress, a phenomenon known as resilience. They exhibit extraordinary resilience, maintaining normal function despite severe stress exposure.

Understanding the biological factors behind their stamina could give us clues to prevent mental illness in other youngsters.

"Two-hit" stress model - rubbing salt in the wound.
The first few weeks of life are crucial for brain development. Research in rodents has demonstrated that maternal care influences gene expression in the hippocampus, a key region in stress regulation - and that in mammals, maternal behavior has a lasting impact on stress responses.

One key factor that influences resilience is early-life experience. Early-life stress can increase sensitivity to developing depression in adolescence, aligning with the "two-hit" stress model.

The two-hit stress model suggests that early-life stress can make individuals more vulnerable to mental health disorders when they face additional stress later in life.

The first "hit" occurs during a critical developmental stage, such as infancy, when environmental stressors, like maternal neglect or trauma, affect brain development.

The second "hit" occurs later, often in adolescence, when new stress adds to those early struggles, increasing the risk of conditions like depression or anxiety.

This model helps explain why some people develop mental health issues while others don’t, showing how early experiences can shape how we respond to stress throughout life.

One way this happens is through changes in mitochondrial function—tiny energy-producing structures in our cells that are essential for brain activity.

Mitochondria: The powerhouse of energy (and resilience?)
Mitochondria, essential for cellular energy production, play a critical role in mental health.

Researchers have found that stress-related depression in adolescence is linked to problems in mitochondrial function, especially in a part of the brain called the medial prefrontal cortex, which helps regulate emotions.

Chronic stress increases mitochondrial destruction by fragmentation. Experiments have shown that this demolition of the little powerhouses could be caused by overactivation of a specific protein (Dynamin-Related Protein 1) in the medial prefrontal cortex of the brain.

Blocking that protein restores mitochondrial function and reduces depressive symptoms, suggesting that targeting mitochondrial stability may offer a therapeutic approach for adolescent stress and depression.

Mum, protect my brain, please - maternal care and brain resilience
Experimental models demonstrate that improved maternal behavior correlates with greater stress resistance in adolescence. These findings suggest that early-life interventions aimed at enhancing parental care may confer long-term mental health benefits.

But how does that work on a molecular level?

Recent research has identified a molecular link between maternal care and stress resilience. The researchers found that when a mother provides strong, consistent care, the brain produces more of a protective protein called IGF-1 (insulin-like growth factor-1).

IGF-1 is quite similar to insulin, a hormone that helps regulate blood sugar, but IGF is mainly involved in promoting the growth of cells and tissues, especially during childhood and adolescence.

This protein, IGF-1, is released by brain immune cells, and it turns out that it also helps block the stress-related activity of that bad protein mentioned above (Dynamin-Related Protein 1).

In other words, increased maternal care increase IGF-1 levels, preventing destruction of the mitochoindria and fostering resilience and reducing the risk of depression in offspring.

That's incredibly interesting!

Understanding Adolescent Mental Health
Despite progress in elucidating adolescent stress resilience, gaps remain.

As an example, paternal influences on brain development are less understood.

Another emerging area of interest is the gut-brain axis, as gut microbiota may modulate IGF-1 levels and stress responses.

No matter what - the growing evidence underscores the significance of preventing early-life neglect - and points to the mitochondrial function as a promising new therapeutic target in treatment.

About the scientific paper:

First author: Hongyu Chen, China
Published: Nature Communications, March 2025
Link to paper:  https://www.nature.com/articles/s41467-025-57810-w