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For the first time, researchers at King's College London and the University
of Florence have identified the specific genetic blueprint of mania, the
defining feature of bipolar disorder. Bipolar disorder is one of the most
severe and complex psychiatric conditions, affecting around 2% of people
worldwide.
The work appears in Biological Psychiatry.
While episodes of depression, psychosis and other symptoms are common,
mania is what distinguishes bipolar disorder from other mental illnesses. Mania
is a state of persistently elevated or irritable mood marked by increased
energy, reduced need for sleep, rapid thoughts and speech, and in some cases,
impaired judgment, impulsive behavior or psychotic symptoms.
Until now, however, the biology of mania has been difficult to study
because many people with a diagnosis of bipolar disorder also have episodes of
depression and psychosis, making it hard to determine what is specific to
bipolar disorder itself.
To uncover the genetic basis of mania, the researchers used data from very
large international genetic studies, including more than 27,000 people with
severe bipolar disorder and over 576,000 individuals studied for depression.
They applied an advanced statistical approach that
allowed them to separate the genetic signals for mania from those for
depression.
In simple terms, this method works by subtracting the genetic effects
associated with depression from those seen in bipolar disorder, leaving behind
the genetic component that is specific to mania. This made it possible to study
mania as its own biological process for the first time.
The study found that mania accounts for more than 80% of the genetic
variation in bipolar disorder, underlining its central role in the condition.
The researchers identified 71 genetic variants linked specifically to mania,
including 18 regions of genes that had never previously been associated with
bipolar disorder. Many of these genes are involved in voltage-gated calcium channels, which are
essential for communication between brain cells and for regulating mood.
When compared genetically with other traits, mania showed a distinct profile, sharing less genetic overlap with
substance use and more with measures related to well-being and educational
attainment than bipolar disorder as a whole.
Understanding the genetics of mania is critically important because it
offers a direct window into the core biology of bipolar disorder. Many people
with bipolar disorder first seek help during depressive or other types of
episodes, when the condition can look very similar to severe depression or
schizophrenia. As a result, individuals can spend up to a decade moving between
different diagnoses before bipolar disorder is correctly identified.
By defining the genetic features that are unique to mania, this research
moves the field closer to identifying early biological indicators of bipolar
disorder, with the potential to shorten this diagnostic journey and ensure
people receive the right treatment sooner.
Important implications for diagnosis and treatment
These findings have important implications for diagnosis and treatment.
Psychiatrists currently distinguish between several forms of bipolar disorder,
such as bipolar type I, bipolar type II and cyclothymia, largely based on
patterns of mood episodes over time. A clearer understanding of the biology of
mania may help refine these distinctions, identify additional subtypes, and
support more personalized approaches to care.
The results also highlight potential treatment pathways, including
calcium-channel mechanisms, and suggest that established medications such as
lithium may exert their effects through these biological systems.
Dr. Giuseppe Pierpaolo Merola, MRC Clinical Research Training Fellow,
Institute of Psychiatry, Psychology & Neuroscience, King's College London,
lead author of the study, said, "By isolating the genetic architecture of
mania, we have taken a crucial step towards understanding the core biology of
bipolar disorder. This allows us to see what makes mania distinct, rather than
viewing bipolar disorder simply as a mixture of mania, depression and
psychosis, and opens new possibilities for more precise and personalized
treatments."
Professor Gerome Breen, Professor of Psychiatric Genetics at King's College
London and Mental Health BioResource Lead at the NIHR Maudsley Biomedical
Research Centre, added, "Mania is what defines bipolar disorder, yet it
has remained surprisingly difficult to study in its own right. Our research on
the genetics of mania gives us a clearer picture of its biology and how it
differs from other psychiatric conditions. In the longer term, this could help
clinicians recognize bipolar disorder earlier, reduce the long delays many
patients face before receiving a diagnosis, and improve outcomes through more
targeted treatment."
The research was conducted at the Institute of Psychiatry, Psychology & Neuroscience at King's College London in collaboration with the University of Florence.
Source: Researchers identify genetic blueprint of mania in bipolar disorder
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