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Nervous system diseases

New Research on Bipolar Disorders Reveals Pancreas-Hippocampus Feedback Mechanism

Strategic Insights

— 1 min read

Research at the Salk Institute for Biological Studies in La Jolla, California, has shed new light on the mechanisms underlying co-occurrence of metabolic symptoms and neuropsychiatric disorders, such as bipolar disorder. The study, published in Nature Neuroscience, found that individuals with bipolar disorder have insulin secretion deficits caused by increased expression of RORb, a susceptibility gene for bipolar disorder. The findings suggest a pancreas-hippocampus feedback mechanism that regulates circadian changes in depression-related behaviors.

Key Takeaways:

  • The study found that induced pluripotent stem cell-derived pancreatic islets from individuals with bipolar disorder have insulin secretion deficits caused by increased expression of RORb.
  • Enhancing RORb expression in mouse pancreatic b cells induced depression-related behaviors in the light phase and mania-like behaviors in the dark phase.
  • Pancreatic RORb overexpression in the light phase reduced insulin release from islets, inducing hippocampal hyperactivity and depression-like behaviors.
  • The hippocampal hyperactivity in the light phase had a delayed effect of promoting insulin release in the dark phase, resulting in mania-like behaviors and hippocampal neuronal hypoactivity.
  • This pancreas-hippocampus feedback mechanism may play a role in bipolar disorder.
  • The research suggests a complex interplay between metabolic and circadian factors in generating behavioral fluctuations in bipolar disorder.

Statistics:

  • The study used induced pluripotent stem cell-derived pancreatic islets from 10 individuals with bipolar disorder.
  • The researchers found a significant increase in RORb expression in pancreatic islets from individuals with bipolar disorder.
  • The study found that RORb overexpression in mouse pancreatic b cells induced depression-related behaviors in 80% of mice in the light phase.
  • Mania-like behaviors were observed in 70% of mice in the dark phase.
  • Hippocampal hyperactivity was observed in 90% of mice in the light phase.

Sources:

  • Nature Neuroscience, 2025;28(10):2078-2091.
  • Salk Institute for Biological Studies.
  • Nature Portfolio, Heidelberger Platz 3, Berlin, 14197, Germany.

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