Bipolar disorder is not just a “mood swing” or a passing emotional shift. It is a serious psychiatric condition that profoundly shapes the lives of millions of people worldwide. Those who live with it often describe life as a rollercoaster: moments of deep despair, where even the simplest daily tasks feel impossible, alternating with bursts of euphoric energy and sleepless nights filled with racing thoughts.
On average, about 1–2% of people across the globe are diagnosed with bipolar disorder at some point in their lives. For many, it can be debilitating—impacting relationships, careers, physical health, and overall quality of life. Yet despite decades of research, the biological underpinnings of bipolar disorder remain elusive. Why do the brain and body shift so dramatically between states of depression and mania? What makes some people more vulnerable to this disorder than others?
Looking Beyond the Brain
For a long time, scientists have focused almost exclusively on the brain when studying bipolar disorder. This makes sense—after all, mood and behavior are directly connected to neural circuits and chemical signaling. But recent research has begun to reveal that bipolar disorder is not just a “brain disorder.” Instead, it may also involve the body in surprising ways.
One striking clue comes from the fact that many individuals with bipolar disorder also show metabolic changes, particularly problems with blood sugar regulation. These changes can resemble the early signs of diabetes, suggesting that mood instability and metabolism might be more closely intertwined than once thought. But how could shifts in blood sugar and insulin—the hormone that allows the body to process energy from food—possibly be linked to the extremes of mania and depression?
A Surprising Genetic Connection
Researchers at Tsinghua University, the Chinese Academy of Sciences, and several collaborating institutions recently uncovered a remarkable biological bridge between the pancreas and the brain. Their study, published in Nature Neuroscience, focused on a gene known as RORβ (RAR-related orphan receptor beta), which has been identified as a susceptibility gene for bipolar disorder.
Using stem cell technology, the researchers generated pancreatic cells from individuals with bipolar disorder. These clusters of cells, called islets, normally regulate blood sugar by producing insulin. To their surprise, the scientists found that in bipolar patients, these cells had a serious malfunction: the RORβ gene was overactive, disrupting insulin release.
This was more than a local problem in the pancreas. Somehow, it was also feeding back to the brain—specifically the hippocampus, a region involved in memory and emotional regulation.
The Pancreas–Brain Feedback Loop
To dig deeper, the team turned to animal models. In mice, they artificially increased the expression of RORβ in β cells—the insulin-producing cells of the pancreas. What they observed was striking.
During the daytime, when mice are usually quiet and resting, the altered animals showed depression-like behaviors—low energy, reduced interest in activity, and signs of negative affect. This was linked to reduced insulin release and heightened hippocampal activity. But at night, when mice are typically active, the same animals shifted into mania-like behaviors: increased movement, heightened arousal, and impulsivity.
In other words, changes in insulin release from the pancreas seemed to directly influence neural circuits in the hippocampus, creating an oscillation between depressive and manic states. The researchers described it as a pancreas–hippocampus feedback loop, where metabolic signals and circadian rhythms combine to produce dramatic mood fluctuations.
Why This Matters
This discovery is more than a fascinating scientific insight—it could reshape how we understand and eventually treat bipolar disorder. For decades, treatments have largely focused on mood stabilizers and psychiatric medications aimed at the brain. While these drugs help many, they often come with side effects and don’t work for everyone.
The new findings suggest that therapies targeting metabolism—whether through regulating insulin, modifying diet, or even developing drugs that address pancreatic gene expression—might one day complement or even enhance traditional psychiatric treatments.
More broadly, this research highlights the importance of seeing the body as an interconnected system. Mental health is not isolated from physical health; instead, they are deeply entwined. The idea that a shift in pancreatic function could ripple into the brain, shaping emotion and behavior, is a powerful reminder of the body’s complexity.
Living With Bipolar Disorder
For those who experience bipolar disorder firsthand, these scientific advances carry a message of hope. They remind us that the condition is not a personal failing or weakness—it is rooted in biology, shaped by genes, cells, and the hidden conversations between different organs. Understanding these processes could pave the way for more compassionate, effective, and holistic treatment strategies.
Yet, beyond the science, it is important to remember the human side. Living with bipolar disorder can be isolating and frightening, but it can also be manageable with the right support. Therapy, medication, social connection, lifestyle strategies, and—perhaps in the future—new treatments inspired by discoveries like the RORβ gene study all hold the potential to help individuals lead stable, fulfilling lives.
A New Frontier of Discovery
The study from Liu, Weng, and their colleagues opens a new frontier in psychiatry. By showing how a gene in pancreatic cells can influence mood states via a feedback loop with the hippocampus, they have revealed an entirely new dimension of bipolar disorder biology.
Much work remains. Human studies must confirm whether the pancreas–brain loop functions the same way in people as in mice. Researchers will need to explore how circadian rhythms, diet, and environmental stressors interact with these pathways. But one thing is clear: the door has been opened to a richer, more integrated understanding of mental health.
Bipolar disorder, once thought of as purely a psychiatric condition, may in fact be a story of the whole body—a story in which the pancreas and the brain dance together, sometimes in harmony, sometimes in painful disarray. And by listening more closely to this hidden dialogue, science may one day bring balance back to the lives of those living with this condition.
More information: Yao-Nan Liu et al, A pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-02040-y.
