Mapping the Cerebrospinal Fluid Proteome in Bipolar Disorder

Area of Science:

• Neuroscience
• Proteomics
• Psychiatry

Background:

• Bipolar disorder (BD) is a severe psychiatric condition with an unclear etiology and no established biomarkers.
• Characterizing the cerebrospinal fluid (CSF) proteome in euthymic individuals with BD is crucial for identifying potential protein biomarkers.

Purpose of the Study:

• To characterize the cerebrospinal fluid (CSF) proteome in euthymic individuals with bipolar disorder (BD).
• To identify potential protein biomarkers for BD through large-scale proteomic profiling.

Main Methods:

• Utilized nano-flow liquid chromatography coupled with high-resolution mass spectrometry.
• Quantified over 2000 CSF proteins in 374 individuals across two independent clinical cohorts.
• Conducted longitudinal analyses and association studies with genetic risk loci.

Main Results:

• Identified 41 differentially abundant proteins in CSF between BD cases and controls.
• Observed lower levels of synaptic and axon guidance proteins, and higher levels of blood-brain barrier and complement proteins.
• Found dynamic changes in CSF proteome composition correlating with clinical outcomes and disease severity.

Conclusions:

• This study provides the first large-scale untargeted CSF proteome profiling in BD.
• Unveiled potential protein biomarkers indicative of altered synaptic function, brain connectivity, and neurovascular integrity in BD.
• Offers in vivo support for the roles of synaptic alterations, impaired neurovascular integrity, and complement activation in BD pathology.