What Causes Migraines? Genes, the Brain and Triggers

What causes migraine?

Migraine is a disorder of the brain, and it runs in families. It affects more than a billion people worldwide.¹

For much of the twentieth century it was thought to be a problem with blood vessels in the head. That theory has been set aside. Researchers now describe migraine as an inherited tendency for the brain to lose control of its inputs: a disorder of how the brain processes sensory signals such as light, sound, smell and pain.² The widening of blood vessels seen during an attack is a side effect, not the cause.³

Is migraine genetic?

To a large degree. A study of almost 30,000 pairs of twins in six countries, including Australia, estimated that genes account for between 34 and 57 per cent of a person’s susceptibility to migraine.⁴

There is no single migraine gene. The largest genetic study so far compared more than 100,000 people with migraine against 770,000 without and found 123 regions of the genome linked with the condition. They involve both the nervous system and blood vessels.⁵ A few rare forms of migraine are caused by a change in one gene, but these are the exception.³

If one of your parents has migraine, you are more likely to have it too. It is nobody’s fault.

What happens in the brain during an attack?

An attack unfolds in stages, and the headache is only one of them.²

• The warning phase. Hours to days before the pain, deep brain areas that regulate sleep, appetite and sensory input start to behave differently. This produces tiredness, yawning, food cravings, thirst, and sensitivity to light and sound⁶
• Aura. In about one in three people, a slow wave of electrical activity spreads across the surface of the brain, causing flashing lights, zigzag lines or tingling^3,7
• The headache. Pain nerves that supply the coverings of the brain become activated and sensitised, which is why the pain throbs and movement makes it worse²
• Recovery. A day or so of feeling washed out

See migraine symptoms and migraine aura.

Causes and triggers are different things

A cause is why you have migraine at all. That is mostly your genes and how your brain is wired. A trigger is something that sets off an attack in a brain already prone to them.

A useful way to picture it is a threshold. Everyone’s brain has one, and in migraine it sits lower. On a good day you can miss lunch and nothing happens. When you are short of sleep, stressed and premenstrual, the same missed lunch tips you over.

Common migraine triggers

In a meta-analysis of 85 studies and more than 27,000 people, four in five people with migraine or tension-type headache named at least one trigger. The most common were stress, reported by 58 per cent, and sleep, reported by 41 per cent.⁸ Others that people often report include:⁷

• Missing meals
• Too much or too little sleep
• Hormonal changes around periods or menopause
• Bright lights, loud noise and strong smells
• Alcohol
• Changes in the weather

The “let-down” migraine

Many people get migraines on weekends or at the start of a holiday. A diary study found that the level of stress on a given day did not predict attacks. A drop in stress from one day to the next did, raising the odds of a migraine over the following hours by 50 to 90 per cent.⁹

Do triggers hold up when they’re tested?

Often they don’t.

• Chocolate. In a double-blind trial, people with headaches were given chocolate or a look-alike made from carob. Chocolate was no more likely to bring on a headache, even in people who were sure it was a trigger for them¹⁰
• Light and exercise. Danish researchers exposed 27 people with migraine with aura to the triggers they had named themselves, mostly bright or flickering light and hard exercise. Only three had their usual attack. None reacted to light alone¹¹

One explanation is that the “trigger” is sometimes the first symptom. Craving sweet food, being bothered by light and feeling tired are all part of the warning phase.⁶ If you eat chocolate because an attack has already started, it will look like the chocolate caused it.

This is good news in a way. Long lists of banned foods are rarely needed, and strict avoidance can make life smaller without reducing attacks.

Hormones and migraine

Migraine is two to three times more common in women than in men, and the female sex hormones are a major reason.¹² Many women notice attacks around their period, and changes at puberty, in pregnancy and around menopause. See perimenopause.

Who is more likely to get migraine?

• People with a family history⁷
• Women¹²
• People with depression or anxiety, asthma, or other long-term pain conditions^7,12

What you can do with this

• Keep things regular. A steady routine of sleep, meals, fluids and caffeine keeps you further from your threshold
• Keep a diary for a couple of months before deciding what your triggers are. Look for combinations, not single culprits
• Don’t over-restrict. Only cut out a food if it reliably brings on an attack
• Exercise regularly and manage stress. See migraine relief
• Talk to your doctor if attacks are frequent. Preventive treatment can raise the threshold

When to see a doctor

• Your headaches are frequent, or stop you from doing normal things¹³
• Your headaches have changed in pattern or become more severe¹³
• You have aura symptoms for the first time, or an aura that lasts more than an hour
• You are using pain relief for headaches more than two or three days a week

Call 000 for a sudden, severe headache, or a headache with confusion, weakness, trouble speaking, fever or a stiff neck.¹³

References

1. Ashina M, Katsarava Z, Do TP, et al. Migraine: epidemiology and systems of care. Lancet. 2021;397(10283):1485-1495.
2. Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev. 2017;97(2):553-622.
3. Ferrari MD, Goadsby PJ, Burstein R, et al. Migraine. Nat Rev Dis Primers. 2022;8(1):2.
4. Mulder EJ, Van Baal C, Gaist D, et al. Genetic and environmental influences on migraine: a twin study across six countries. Twin Res. 2003;6(5):422-31.
5. Hautakangas H, Winsvold BS, Ruotsalainen SE, et al. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat Genet. 2022;54(2):152-160.
6. Karsan N, Goadsby PJ. Biological insights from the premonitory symptoms of migraine. Nat Rev Neurol. 2018;14(12):699-710.
7. healthdirect. Migraine.
8. Pellegrino ABW, Davis-Martin RE, Houle TT, et al. Perceived triggers of primary headache disorders: A meta-analysis. Cephalalgia. 2018;38(6):1188-1198.
9. Lipton RB, Buse DC, Hall CB, et al. Reduction in perceived stress as a migraine trigger: testing the "let-down headache" hypothesis. Neurology. 2014;82(16):1395-401.
10. Marcus DA, Scharff L, Turk D, et al. A double-blind provocative study of chocolate as a trigger of headache. Cephalalgia. 1997;17(8):855-62; discussion 800.
11. Hougaard A, Amin FM, Hauge AW, et al. Provocation of migraine with aura using natural trigger factors. Neurology. 2013;80(5):428-31.
12. Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76-87.
13. healthdirect. Headaches.