There is an overlap between migraine and depression in our brains

Migraine and depression might seem like very different conditions. One causes throbbing pain in your head; the other drags your mood down and dims your joy.

But they often show up together—and not by chance.

Studies show that people with depression are about twice as likely to suffer from migraines, and those with migraines are two to three times more likely to be diagnosed with depression.

In this post, we try to uncover the link between the two diseases.

Signals in the brain 
Though their symptoms differ, migraines and depression share similar patterns deep in the brain.

Genetics plays a major role in this overlap. Large studies have found that both disorders involve changes in the same genes, especially those related to brain cell communication, mood regulation, and pain.

For example, genes that affect levels of serotonin and dopamine, two important brain messengers, are involved in both conditions. Other molecules like CGRP, which help regulate blood vessels and pain sensitivity, previously thought to be only linked to migraine, also seem to be involved in depression.

Brain scans reveal that certain areas, like the amygdala, thalamus, and prefrontal cortex, show unusual activity in both depression and migraine, suggesting that emotional processing and sensory overload are wired together in complex ways in both conditions.

Shared treatments, shared mechanisms 
Perhaps it is then not so surprising that many drugs used to treat one disorder also help with the other.

Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors (called SNRIs) are prescribed to ease both depression and chronic migraines. Even more experimental treatments like ketamine and psilocybin, which target serotonin systems, have shown promise in both conditions.

Medications that block CGRP help reduce the number of migraine attacks and also seem to lift mood in people with the comorbidity.

Hormones like estrogen and vitamins like B2 also seem to influence both headache and mood symptoms in some.

Interestingly, some medications like topiramate can help with migraine but may worsen depression in certain individuals, highlighting how delicate the brain's chemical balance really is.

Sensitive systems and stress links 
Both migraine and depression are stress-sensitive disorders. Stress, especially early in life, can set the stage for both conditions by affecting the structure of brain circuits involved in mood and pain.

Repeated stress lowers the brain’s threshold for pain and mood regulation, making it easier for both headaches and sadness to break through.

Animal studies also show that early life adversity can change the development of brain areas critical for emotion and pain processing. Female brains seem especially vulnerable to such changes, potentially explaining why both disorders are more common in women. Hormones like estrogen and prolactin (a hormone that comes into play during pregnancy and lactation) interact with stress and may amplify these effects.

The gut-brain axis also plays a role: differences in gut bacteria have been linked to both depression and migraine, with diet and probiotics influencing symptoms in early research.

Electric storms and brain circuits 
Finally, the way the brain’s networks light up and communicate matters.

In both disorders, brain imaging reveals that circuits regulating emotion, attention, and sensory input are off balance. Some areas are hyperactive or poorly connected compared to healthy people. This may explain why people with both migraine but also with depression often feel overwhelmed by noise or light, symptoms we usually associate with migraine.

Disrupted circuits in the brainstem, our oldest, deepest part of the brain, also appear to play roles in both disorders by controlling the release of key chemicals like serotonin and norepinephrine. These regions govern sleep, pain, arousal, and mood—functions that go awry in both migraine and depression.

Together, this growing body of evidence paints a picture of migraine and depression not as separate issues but as overlapping brain conditions.

Understanding their shared biology could lead to better, more personalized treatments for people who live with both. And that´s millions of people ..

About the paper that inspired:

First Author: Micah Johnson, USA
Published: The Journal of Headache and Pain, July 2025
Link to paper: https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-025-02097-x

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