Stress rewires your brain circuits to fuel anxiety and depression

Anxiety disorders, depression and stress are not fringe concerns. In 2021, anxiety affected 359 million people, while depression affected 332 million people.

“In 2021 alone, nearly 700 million people were affected globally,” said Professor Wei-Hua Yue, dean of the Peking University Sixth Hospital. “Together, these disorders account for more than 90 million years of healthy life lost each year.”

A new comprehensive review of how stress changes the brain – and how those changes relate to anxiety and depression – pulls together evidence on neurotransmitters, hormones, genes, inflammation, and the wiring of neural circuits.

Stress alters brain’s wiring system

The lead voice behind the review, centering on a circuit-focused approach, is Bing-Xing Pan, dean of the Institute of Biomedical Innovation at Nanchang University. His team links specific brain pathways to the symptoms people feel.

“We think of neural circuits as the brain’s intricate wiring system, networks of neurons that communicate to regulate specific functions,” said Pan. The point is to study connections in action rather than isolated regions.

By measuring activity in single cells and larger populations – and by carefully altering circuit function – scientists can link networks to behavior. That shift opens the door to targeted tests and treatments. Instead of simply observing symptoms, researchers can now see how certain brain signals cause those feelings or actions.

This deeper insight makes it possible to design therapies that focus on repairing the right connections rather than using a broad trial-and-error approach.

With time, these discoveries could lead to highly personalized care, where doctors match treatments directly to brain activity patterns – offering more effective and lasting relief for patients.

Brain pathways explain symptoms

Animal and human studies show that disrupted prefrontal cortex control over the amygdala tracks with pathological anxiety. Pan puts this pattern into everyday terms.

“For instance, we recently identified that hyperactivity in the prefrontal-amygdala circuit is strongly linked to anxiety-like behaviors,” said Pan.

The finding ties fear processing to a specific pathway that doctors may one day be able to measure and modulate.

“Reduced function in the hippocampus-nucleus accumbens circuit is associated with anhedonia, a core symptom of depression,” explained Pan. That connection helps explain why pleasure and motivation can fade when stress and mood disorders set in.

Independent reviews report that the lateral habenula often acts like an anti-reward center in depression. Overactivation of the lateral habenula – often called the brain’s “anti-reward center” – has been linked to elevated depression-like behaviors

Current drugs fall short

Clinical data from early 2024 show that emotional blunting can occur with commonly used serotonergic antidepressants. Rates in one clinical program ranged from 43 to 47 percent across several SSRIs.

“Not all patients respond well. Side effects such as weight gain and emotional blunting are common,” said Professor Yue. Many people need options that fit their biology more closely.

Response can also vary with stress history, age, and coexisting conditions. A one-size-fits-all plan does not match the variety seen in clinics.

Targeting brain stress circuits

The review points to circuit-specific ideas for intervention, including neuromodulation that targets misfiring pathways. Mapping symptoms to circuits makes it easier to test whether a therapy hits the right spot.

Sensors, imaging, and blood-based biomarkers could guide choices and track progress. That is the promise of precision psychiatry – data, not trial and error, drive selection.

Future investigations are expected to bring advanced technologies into everyday medical practice, speed up the identification of dependable biomarkers, and encourage the design of treatments that can be applied across different diagnoses.

The hope is that recognizing common biological features among disorders will make it possible to develop more effective tools more quickly.

Impact of stress on brain

For someone sitting in a clinic, this arc of research matters. A symptom like constant worry can reflect a pattern in prefrontal amygdala signaling that points to a specific treatment plan.

For someone who cannot feel joy, it can signal a weakened line between the hippocampus and nucleus accumbens that needs support. The more we link symptoms to circuits, the easier it becomes to match therapies to people.

This approach moves beyond general labels like “anxiety” or “depression” and instead ties experiences to the specific brain networks involved. For example, when doctors know which pathway is underactive or overactive, they can suggest treatments that directly address that imbalance.

Over time, this could mean fewer side effects, quicker recovery, and more hope for individuals who feel stuck with ineffective options.

The study is published in the journal Science China Life Sciences.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–