Refining patterns of MEF2C effects in white matter microstructure and psychiatric features

Area of Science:

• Neurogenetics
• Psychiatric Genetics
• Neuroimaging

Background:

• Myocyte Enhancer Factor 2 C (MEF2C) gene variants are associated with white matter microstructure and psychiatric disorders.
• MEF2C plays a role in neuronal development pathways, suggesting a shared biological basis for these phenotypes.

Purpose of the Study:

• To investigate the specific effects of MEF2C gene variants on brain white matter microstructure and psychiatric phenotypes.
• To integrate analyses of white matter and psychiatric data in a well-characterized Brazilian adult sample.

Main Methods:

• Utilized gene-wide and Single Nucleotide Polymorphism (SNP) analyses to evaluate MEF2C variants in 870 Brazilian adults.
• Assessed psychiatric phenotypes via standardized interviews and brain imaging (magnetic resonance imaging) in 139 participants.
• Examined associations between MEF2C variants and fractional anisotropy (FA) in white matter tracts.

Main Results:

• Gene-wide analysis revealed a nominal association between MEF2C and the Temporal Portion of the Superior Longitudinal Fasciculus (SLFTEMP).
• SNP analysis identified four independent variants significantly associated with SLFTEMP.
• One variant (rs4218438) was significantly associated with Substance Use Disorder.

Conclusions:

• MEF2C variants show specific associations with components of the temporal-frontal circuitry.
• These findings may elucidate the role of the MEF2C gene in the etiology of a spectrum of psychiatric phenotypes.
• The temporal-frontal circuitry is crucial for executive and cognitive functions relevant to psychiatric disorders.