New Study Reveals Mania Drives Over 80% of Bipolar Disorder’s Genetic Architecture

Bipolar disorder has confused doctors, frustrated patients, and resisted easy answers for decades. People living with the condition can wait up to ten years before receiving the right diagnosis. During that time, they bounce between labels like major depression and schizophrenia while their symptoms rage on without proper treatment. But a major new study may have cracked open a mystery that psychiatry has been chasing for years. Researchers have identified the genetic fingerprint of mania, and what they found could reshape everything we thought we knew about bipolar disorder. What surprised them most was not what causes the condition. It was how lopsided the answer turned out to be.

A Tug of War Inside Your Brain

Picture bipolar disorder as a rope being pulled in two directions. Depression yanks one way. Mania yanks the other. For years, most people assumed the pull was roughly equal, that both ends contributed similar force to the condition. Researchers at King’s College London and the University of Florence just proved that assumption wrong.

After analyzing genetic data from more than 600,000 people (including over 27,000 diagnosed with bipolar disorder), the team discovered that mania accounts for about 81.5% of bipolar disorder’s genetic makeup. Depression? Just 18.5%.

In other words, mania is not just one feature of bipolar disorder. It is the dominant driver. And that changes everything about how we should think about diagnosis, treatment, and the biology behind the condition.

What Exactly Is Mania?

Before we go further, let’s make sure we are on the same page about mania. It is not just feeling “hyper” or having a good day. Mania is a state of persistently elevated or irritable mood, packed with racing thoughts, rapid speech, surging energy, and a reduced need for sleep.

Some people in manic episodes feel invincible. They make impulsive decisions, spend money recklessly, or engage in risky behavior. In severe cases, mania can trigger psychotic symptoms like hallucinations or delusions.

What makes mania so tricky from a medical standpoint is that it often hides behind other symptoms. Many people with bipolar disorder first seek help during a depressive episode. At that point, the condition looks almost identical to major depression. Without a clear manic episode on record, doctors may prescribe antidepressants that can actually make bipolar symptoms worse.

How Scientists Pulled Mania Apart from Depression

Studying mania has always been difficult because bipolar disorder bundles several conditions together. Patients experience depression, mania, and sometimes psychosis, often in overlapping cycles. Separating the genetic signals for each has been like trying to hear one instrument in an orchestra.

Researchers solved that problem with an advanced statistical method. Using genome-wide association study (GWAS) data, they subtracted the genetic effects linked to major depressive disorder from the overall bipolar disorder signal. What remained was the genetic blueprint of mania on its own.

Dr. Giuseppe Pierpaolo Merola, the study’s lead author and a research fellow at King’s College London, described the approach as a way to see what makes mania distinct rather than viewing bipolar disorder as a blended mix of symptoms.

Published in the journal Biological Psychiatry, the study represents the first time scientists have been able to study mania as its own biological process, separate from depression and psychosis.

71 Genetic Variants and 18 Brand New Discoveries

When the team isolated mania’s genetic signature, the results were striking. They identified 71 genetic variants connected to mania, spread across 37 regions of the genome. Of those, 18 gene regions had never been linked to bipolar disorder before.

Many of these genes connect to traits that line up with what mania looks and feels like: reduced sleep needs, elevated mood, high physical activity, night-owl tendencies, and a taste for risk-taking behavior like speeding.

But here is where it gets interesting. Some behaviors we commonly associate with mania, such as substance abuse and risky sexual behavior, showed weaker genetic connections to the mania variants. That suggests those symptoms may not actually be driven by mania itself. Instead, they may stem from other factors or co-occurring conditions.

For patients and clinicians alike, that distinction matters. It could mean that certain behaviors currently treated as core symptoms of bipolar disorder might need a different therapeutic approach altogether.

Calcium Channels: A Promising Treatment Target

Among the most exciting findings from the study was a clear signal pointing to voltage-gated calcium channels. Several of the mania-linked genes affect these channels, which play a key role in how neurons communicate with each other and regulate mood.

Calcium channels act like gates in your brain cells. When they open and close properly, nerve signals flow smoothly. When they malfunction, communication between neurons breaks down, and mood regulation suffers.

If mania is driven partly by calcium channel dysfunction, that opens a door for targeted drug development. Interestingly, the findings also suggest that lithium, one of the oldest and most effective treatments for bipolar disorder, may work precisely through these calcium channel systems. Doctors have prescribed lithium for decades without fully understanding why it works. Now, the genetic evidence may be catching up to what clinical experience has long suggested.

Professor Gerome Breen, senior author of the study and a professor of psychiatric genetics at King’s College London, noted that understanding mania’s genetics gives a clearer picture of its biology and how it differs from other psychiatric conditions.

Why Bipolar Disorder Gets Misdiagnosed So Often

One of the most painful realities for people with bipolar disorder is the diagnostic delay. On average, patients spend up to a decade cycling through incorrect diagnoses before a doctor correctly identifies bipolar disorder.

Why does that happen? Because most people seek help during depressive episodes, not manic ones. Depression is the symptom that drives people to the doctor’s office. Mania, on the other hand, can feel productive or even euphoric in its early stages. Patients may not recognize it as a problem, and doctors may not see it if the patient walks in during a low period.

Without catching the manic side of the equation, clinicians often diagnose major depression or, in cases with psychotic features, schizophrenia. Both lead to treatment plans that miss the mark for bipolar disorder.

By mapping mania’s genetic fingerprint, researchers hope to develop early biological indicators that flag bipolar disorder before a patient endures years of misdiagnosis. A blood test or genetic screen that detects mania-related gene variants could someday shorten that diagnostic journey from a decade to months.

What Makes Mania Genetically Different

When the team compared mania’s genetic profile to bipolar disorder as a whole, they found surprising differences. Mania showed a stronger genetic connection to educational attainment and subjective well-being than overall bipolar disorder did. At the same time, its overlap with substance use was lower than expected.

Mania also showed a weaker genetic link to tiredness, which makes sense given that one of its hallmark features is reduced sleep need and sustained high energy.

These genetic distinctions matter because they suggest mania is not just “bipolar disorder minus depression.” It has its own biological identity, with its own set of risk genes and trait associations. Recognizing mania as a standalone process, rather than half of a pair, could lead to more precise diagnostic categories and better-matched treatments.

Psychiatrists currently split bipolar disorder into subtypes like Bipolar I, Bipolar II, and cyclothymia based mainly on the pattern and severity of mood episodes. A deeper understanding of mania’s genetics could refine those categories or reveal new subtypes that current classification systems miss.

A Step Toward Personalized Treatment

For years, treating bipolar disorder has meant casting a wide net. Mood stabilizers, antipsychotics, and anticonvulsants form the backbone of treatment, but finding the right combination for each patient involves a lot of trial and error.

If mania drives over 80% of the genetic architecture of bipolar disorder, treatments that specifically target mania’s biological pathways could be far more effective than current broad-spectrum approaches. Calcium channel modulators, for example, could become a new class of drugs designed to address mania at its genetic root.

Personalized medicine for bipolar disorder has long felt like a distant goal. But with 71 genetic variants now mapped and calcium channels identified as a key mechanism, the path from lab to clinic is getting shorter.

As Dr. Merola noted, isolating mania’s genetic architecture was a first step toward seeing what makes mania distinct and opening new possibilities for more precise and personalized treatments.

My Personal RX on Supporting Mental Health and Bipolar Disorder Awareness

Bipolar disorder affects about 2% of the global population, and many patients wait years for a correct diagnosis. While genetic research is making strides toward better tools and treatments, you can take active steps right now to support your mental health and brain function. I always remind my patients that mental wellness is not separate from physical wellness. Your brain depends on a healthy gut, quality sleep, proper nutrition, and daily movement to regulate mood and manage stress. Here is what I recommend:

1. Prioritize Consistent Sleep: Disrupted sleep is both a trigger and a symptom of mood disorders. Sleep Max contains magnesium, GABA, 5-HTP, and taurine to help calm your mind, balance neurotransmitters, and promote restorative REM sleep, giving your brain the recovery time it needs each night.
   
2. Know Your Nutrient Gaps: After 40, your body absorbs fewer key nutrients that your brain depends on. Download my free guide, The 7 Supplements You Can’t Live Without, to learn which supplements support energy, sleep, and focus, and how to spot quality products versus junk formulas.
   
3. Exercise for Your Brain, Not Just Your Body: Physical activity boosts blood flow to the brain and releases mood-regulating chemicals like endorphins and BDNF. Aim for at least 30 minutes of movement daily, whether walking, cycling, or stretching.
   
4. Keep a Mood Journal: Tracking your daily mood, sleep patterns, and energy levels helps you and your doctor spot trends early. Even a simple notebook can reveal patterns that lead to faster, more accurate diagnosis.
   
5. Reduce Alcohol and Stimulant Intake: Both alcohol and caffeine can destabilize mood cycles. If you are concerned about mood swings or have a family history of bipolar disorder, reducing both gives your brain a steadier foundation.
   
6. Build a Support Network: Mental health improves when you have people you trust to talk to. Stay connected to friends, family, or support groups, and do not hesitate to seek professional help if mood changes start disrupting your daily life.
   
7. Learn Your Family History: Bipolar disorder has a strong genetic component. If close relatives have been diagnosed, share that information with your healthcare provider so they can monitor your mental health more closely.
   
8. Never Self-Diagnose or Self-Medicate: Mental health conditions require professional evaluation. If you suspect bipolar disorder in yourself or a loved one, schedule a visit with a psychiatrist rather than relying on online assessments or over-the-counter remedies.
   

Source: Merola, G. P., Zvrskovec, J., Wang, R., Li, Y. K., Castellini, G., Ricca, V., Coleman, J., Vassos, E., & Breen, G. (2026). Isolating the genetic component of mania in bipolar disorder. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2025.11.008