New research Links Neurodegenerative Markersโข to Bipolar Disorder, Focusing on the Thalamus
A โฃrecent โstudy conducted โby researchers in japan โฃsheds light on the potential โbiological 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 โto bridge theโ gap in understanding the neuropathology of BD. Their findings were published in Psychiatry andโข Clinical Neurosciences on September 2, 2025.
Previous animal studies โคsuggested the paraventricularโฃ thalamic โขnucleus’s involvement inโ BD, but concrete evidence from human brain tissue was limited. The researchers hypothesized that theโ accumulation ofโ neurodegenerative proteins, known to contribute to neurological diseases,โข might be a factor in BD pathology.โข
To investigate this, the team analyzed postmortem brain tissue from individuals with โBD, focusing on the โparaventricular โthalamus and medial temporal regions. They employed immunohistochemical analysis, utilizing antibodies to โฃdetect key neurodegenerative markers: phosphorylated tau, amyloid ฮฒ, ฮฑ-synuclein, and TDP-43. Theyโข also examined markers associated with granulovacuolar degeneration (GVD), specifically CHMP2B and CK-1ฮด. This allowed forโ a thorough assessment of multiple proteins linkedโค to neurodegenerative โprocesses.
The analysis revealed significantly higher stages of neurofibrillary tangles (NFTs) inโ patientsโ with BD, alongside argyrophilic grain pathology. โBoth are associated โwith the accumulation of tau proteins within brain cellsโ and are commonly observed with aging.โข These findings corroborate previous postmortem and neuroimaging studies โคindicating a greater burden of tau-related pathology in BD, potentially linked to the age of onset of โthe disorder.
Notably, the โstudy โคidentified CHMP2B-positive GVD in the paraventricularโข thalamus in approximately half โof the BD cases – a previously unreported observation. GVD is a form โof neuronal degeneration.
These results suggest โคa potential link betweenโค neurodegenerative protein accumulation,โฃ particularly within the paraventricular thalamus, and the biologicalโข mechanisms โคdriving BD. The findings contribute to a growing body of evidence supporting the idea that BDโ is โขa brain-based disease,โข moving beyond a โฃpurelyโค symptom-focused understanding.
Professor Kato โคbelieves these discoveries could be crucial for future advancements, stating that identifying specific protein pathologiesโข like CHMP2B-positive GVD โฃand tau accumulation may “pave the way for the advancement of new diagnostic tools and targeted therapies.” The researchโข underscores theโข need โคforโ early detection โstrategies,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 โthalamus and higher neurofibrillary tangle Braak stages in bipolarโ disorder. Psychiatry and Clinical Neurosciences.โ doi.org/10.1111/pcn.13891