Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function

Area of Science:

• Neuroscience
• Genetics
• Ophthalmology

Background:

• Beta-B2 crystallin (CRYBB2) is a lens protein found in brain regions like the hippocampus.
• Mouse Crybb2 mutations affect sensorimotor gating (prepulse inhibition) and interneuron numbers, mirroring schizophrenia endophenotypes.

Purpose of the Study:

• To investigate the association between CRYBB2 gene variations and schizophrenia endophenotypes in humans.
• To explore the role of CRYBB2 in cognitive functions and sensorimotor gating.

Main Methods:

• Genotyped 27 single nucleotide polymorphisms (SNPs) in CRYBB2 and flanking regions in 510 schizophrenia patients and 1322 healthy controls.
• Assessed schizophrenia-related endophenotypes including antisaccade task performance, working memory, and sensorimotor gating (P50 ratio).
• Measured CRYBB2 mRNA expression and analyzed functional magnetic resonance imaging (fMRI) signals.

Main Results:

• No direct association between CRYBB2 SNPs and schizophrenia was found.
• Decreased CRYBB2 mRNA expression was linked to specific haplotype blocks.
• These haplotype blocks correlated with poorer antisaccade performance, altered working memory fMRI signals, and reduced sensorimotor gating (P50 ratio).
• Findings were observed in both patients and controls, indicating a general role in cognitive function.

Conclusions:

• CRYBB2 plays a significant role in human antisaccade performance and memory function.
• The study highlights CRYBB2's involvement in brain functions beyond its structural role in the eye.
• These findings provide new insights into the neurobiological functions of CRYBB2.