New research Links Neurodegenerative Markers to Bipolar Disorder, Focusing on the Thalamus
A recent study conducted by researchers in japan sheds light on the potential biological underpinnings of bipolar disorder (BD), specifically investigating the role of the paraventricular thalamic nucleus and medial temporal regions of the brain. Led by Professor Tadafumi Kato of Juntendo University Graduate School of Medicine and Dr.Akito Nagakura from Tokyo Metropolitan Matsuzawa Hospital, the research team aimed to bridge the gap in understanding the neuropathology of BD. Their findings were published in Psychiatry and Clinical Neurosciences on September 2, 2025.
Previous animal studies suggested the paraventricular thalamic nucleus’s involvement in BD, but concrete evidence from human brain tissue was limited. The researchers hypothesized that the accumulation of neurodegenerative proteins, known to contribute to neurological diseases, might be a factor in BD pathology.
To investigate this, the team analyzed postmortem brain tissue from individuals with BD, focusing on the paraventricular thalamus and medial temporal regions. They employed immunohistochemical analysis, utilizing antibodies to detect key neurodegenerative markers: phosphorylated tau, amyloid β, α-synuclein, and TDP-43. They also examined markers associated with granulovacuolar degeneration (GVD), specifically CHMP2B and CK-1δ. This allowed for a thorough assessment of multiple proteins linked to neurodegenerative processes.
The analysis revealed significantly higher stages of neurofibrillary tangles (NFTs) in patients with BD, alongside argyrophilic grain pathology. Both are associated with the accumulation of tau proteins within brain cells and are commonly observed with aging. These findings corroborate previous postmortem and neuroimaging studies indicating a greater burden of tau-related pathology in BD, potentially linked to the age of onset of the disorder.
Notably, the study identified CHMP2B-positive GVD in the paraventricular thalamus in approximately half of the BD cases – a previously unreported observation. GVD is a form of neuronal degeneration.
These results suggest a potential link between neurodegenerative protein accumulation, particularly within the paraventricular thalamus, and the biological mechanisms driving BD. The findings contribute to a growing body of evidence supporting the idea that BD is a brain-based disease, moving beyond a purely symptom-focused understanding.
Professor Kato believes these discoveries could be crucial for future advancements, stating that identifying specific protein pathologies like CHMP2B-positive GVD and tau accumulation may “pave the way for the advancement of new diagnostic tools and targeted therapies.” The research underscores the need for early detection strategies,personalized treatment approaches,and therapies that address the underlying biological causes of bipolar disorder.
Source: Nagakura, A., et al.(2025). Increased granulovacuolar degeneration in the thalamus and higher neurofibrillary tangle Braak stages in bipolar disorder. Psychiatry and Clinical Neurosciences. doi.org/10.1111/pcn.13891
