Bipolar disorder is often described as a disease of extremes: euphoria and depression, hyperactivity and exhaustion, impulsivity and blockage. However, for years scientific research focused mainly on one of these poles. Depression was more studied, more measured and more compared. The mania, however, remained in the background. That imbalance has just changed.
An international team of researchers from the United Kingdom and Italy has managed to identify the genetic variants that exclusively influence mania, separating them for the first time from the depressive component of bipolar disorder.
The symptom that defines the disease
Mania is not an exaggerated state of good mood. It involves persistent insomnia, extreme increased energy, racing thoughts, impulsivity, and in some cases, risky behavior. It is also the feature that differentiates bipolar disorder from other mood disorders.
According to the World Health Organization, the disease affects approximately one in 200 people in the world and usually appears in adolescence or early adulthood. Despite this, its diagnosis continues to be complex and, in many cases, late. Part of the problem is that depressive symptoms take up most of the patient’s clinical time, while manic episodes may be brief or difficult to recognize.
Separate mania from depression
The new study, published in Biological Psychiatry, started from a specific question: does mania have its own genetic basis or does it share the same genes as depression? To answer it, researchers analyzed genetic data from more than 27,000 people with bipolar disorder and compared it with information from more than 576,000 people studied for depression.
The key was in the method. Using an advanced statistical model, the team managed to “subtract” the genetic component of depression from that of bipolar disorder. In this way, they isolated what belongs exclusively to mania. The result was overwhelming.
The genetic core of bipolar disorder
The analysis showed that mania explains 81.5% of the genetic basis of bipolar disorder, while depression accounts for only the remaining 18.5%. In other words: from a genetic point of view, mania is not just another part of the clinical picture, but rather its central core.
The researchers identified 71 genetic variants uniquely associated with mania, distributed across 37 regions of the genome. Of them, 18 had never been linked to bipolar disorder before. Several affect calcium channels in neurons, fundamental structures for communication between brain cells and the regulation of mood.
A different genetic profile
The genetic profile of mania also showed striking differences compared to bipolar disorder analyzed as a whole. A lower association appeared with substance use and a stronger relationship with traits such as subjective well-being and cognitive performance. Even when analyzing cases with psychotic symptoms, mania maintained its dominant genetic weight.
For researchers, this reinforces the idea that the disease cannot be understood solely from depression.
What can change from now on
Understanding the specific genetics of mania could have important practical consequences. According to specialists, this approach would allow:
- improve early diagnosis
- more accurately differentiate subtypes of bipolar disorder
- move towards personalized treatments
It could also help to better understand why drugs such as lithium are effective in some patients and not in others, by acting on the calcium channels identified in the study.
The work has limitations (it only included people of European origin and did not analyze the X chromosome), but it opens a completely new line of research. Mania was no longer a difficult symptom to deal with. Now it has its own genetic map. And with it, the possibility of understanding bipolar disorder from its true center.
