Summary: A new study reveals a pancreatic-hippocampal feedback loop which can help explain mood swings in bipolar disorder. Using pancreatic islets derived from the patient, researchers have found a reduced insulin secretion linked to high Rorβ, a bipolar risk gene.
In mice, the pancreatic overexpression of Rorβ caused depression type behaviors during the day and mania -type behaviors at night by changes in the release of insulin and hippocampal activity. The results suggest that metabolic and mood symptoms in bipolar disorder are linked to a circadian and body brain circuit.
Key facts
- Genetic link: The overexpression of the Rorβ bipolar risk gene in pancreatic β cells has changed insulin release and mood behaviors.
- Circadian dynamics: States of the depression in the light phase were followed by mania-type states in the dark phase, driven by the feedback of the pancreas-end.
- Integrated mechanism: The study identifies a bidirectional loop of pancreas – IPPOCAMPE which can associate a metabolic dysfunction with the instability of the mood.
Why this counts
- Why this counts: Offers a new biological explanation for cooccus competition of metabolic changes and mood swings in bipolar disorder.
- How it aligns with previous research: Bases on evidence connecting insulin signaling, circadian rhythms and psychiatric symptoms.
- Future implications: Could inspire treatments that target pancreatic function or circadian regulation to stabilize mood cycles.
Source: Neuroscience News
For years, researchers have observed that individuals with neuropsychiatric disorders – in particular bipolar disorder – are often present with metabolic symptoms such as alterated glucose regulation or levels of alteration of insulin.
Although the overlap is well documented, the biological ways connecting the metabolic function to the fluctuations of mood have been much less clear.

Now, new research suggests that part of the response can reside in a surprising organs connection: a feedback loop between the pancreas and the hippocampus which is shaped by circadian rhythms.
Using pancreatic islets derived from induced pluripotent stem cells of bipolar disorder, the researchers revealed a distinct cellular anomaly – the secretion of reduced insulin. This alteration was linked to a higher than normal expression of the Rorβ gene, a factor of sensitivity known for bipolar disorder.
Disorder modeling in mice
To better understand how Rorβ could fill metabolic and mood symptoms, the team has designed mice to overexpress the gene specifically in pancreatic β cells. The results were striking: these mice showed depression type behaviors during the light phase of the day and mania -type behaviors during the dark phase – mirging the cyclical mood states observed in bipolar disorder.
At the cellular level, the overexpression of Rorβ during the light phase removed the release of insulin from pancreatic islets. This was accompanied by increased activity in the hippocampus, a region of the brain at the heart of mood regulation, memory and stress response.
Above all, these mood -related effects have not been isolated at a single window; The hippocampal hyperactivity observed in the light phase has triggered a delayed gap of the metabolic function. By the dark phase, the liberation of insulin was high, hippocampal activity has been reduced and mania -type behaviors have emerged.
The pancreatic feedback loop – Hippocampus
This dynamic scheme has revealed a previously unrecognized mechanism: a bidirectional feedback loop in which the signaling of pancreatic insulin influences hippocampal activity and changes in hippocampal function reinstall to affect the pancreatic output. The loop operates on a circadian pace, with disturbances in a phase of the cycle of implementation of changed brain interactions in the next.
The results suggest that, in bipolar disorder, deregulation in this pancreatic circuit – Hippocampus could underlie alternative mood states – depressed stockings and high maniacs – by associating them with changes in the release of insulin and neural activity. Essentially, metabolic and mood symptoms can be both sides of the same biological room.
Beyond the bipolar disorder
Although the study has focused on bipolar disorder, the implications extend to a wider range of neuropsychiatric conditions where metabolic changes and the deregulation of co-Word mood, such as major depressive disorder and schizophrenia. It also raises the possibility that targeting the pancreatic function could indirectly stabilize brain activity and improve mood symptoms.
Since Rorβ is a circadian regulator, work also highlights the potential importance of the effects of the day in research and treatment. Interventions that align or correct or correct circadian disturbances – whether through the drug calendar, light therapy or food models – can help normalize the pancreatic feedback cycle – Hippocampus.
A new integrative model
This research provides a convincing integrative model for bipolar disorder – which poses psychiatry, metabolism and chronobiology. By linking a specific genetic factor to both pancreatic dysfunction and cyclic hippocampal activity, it crops bipolar disorder not only as a brain -based disease but as an entire body condition in which metabolic and neural systems are deeply linked.
Other studies will be necessary to confirm the background loop of the pancreas – hippocampus in humans and determine whether the interventions targeting the regulation of Rorβ or insulin can significantly modify mood cycles. If this is the case, this could open a new therapeutic border – one where body treatment can be as crucial as brain treatment.
About these neuroscience and news of research on bipolar disorders
Author: Editorial team of new neuroscience
Contact: Neuroscience News
Source: Editorial team of new neuroscience – Neuroscience News
Picture: The image is credited with Neuroscience News
Original search: Closed access.
“A pancreatic feedback mechanism – Hippocampus regulates circadian changes in depression behaviors” by Yao -Nan Liu et al. Nature neuroscience
Abstract
A pancreatic feedback mechanism – Hippocampus regulates circadian changes in depression behaviors
People with neuropsychiatric disorders often have metabolic symptoms. However, the mechanisms underlying this coocceca are vague.
Here, we show that the pancreatic islets derived from multipotent stem cells induced by individuals with bipolar disorder have deficits of secretion of insulin caused by an increased expression of RorβA sensitivity gene for bipolar disorder.
Improving the expression of Rorβ in the pancreatic β cells of mouse has induced behaviors linked to depression in the light phase and mania -type behaviors in the dark phase.
The pancreatic overexpression of Rorβ in the light phase has reduced the release of insulin of the islets, inducing hippocampal hyperactivity and depression type behaviors.
In addition, this hippocampal hyperactivity in the light phase had the delayed effect to promote the release of insulin in the dark phase, resulting in mania -type behaviors and hippocampal neuronal hypoactivity.
Our results in mice indicate a pancreatic feedback mechanism – hippocampus by which metabolic and circadian factors cooperate to generate behavioral fluctuations and which can play a role in bipolar disorder.