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CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.

Christian Clemm von Hohenberg1, Marlene C Wigand, Marek Kubicki

  • 1Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA. clemm@bwh.harvard.edu

Journal of Psychiatric Research
|July 23, 2013
PubMed
Summary
This summary is machine-generated.

This study links the CNTNAP2 gene to brain connectivity in schizophrenia patients. A specific gene variant (rs2710126) strongly correlated with white matter structure in the uncinate fasciculus.

Keywords:
AutismCaspr2EndophenotypeGeneticsMagnetic resonance imagingSchizophrenia

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Area of Science:

  • Neurogenetics
  • Neuroimaging
  • Psychiatric Disorders

Background:

  • The CNTNAP2 gene is implicated in neurodevelopmental disorders like autism and schizophrenia.
  • Disruptions in brain connectivity are hypothesized to underlie schizophrenia pathophysiology.
  • CNTNAP2 plays a role in neuronal synchronization and brain connectivity.

Purpose of the Study:

  • To investigate the association between genetic variations in CNTNAP2 and anatomical brain connectivity.
  • To explore the relationship between Diffusion Tensor Imaging (DTI) markers and single nucleotide polymorphisms (SNPs) in CNTNAP2.
  • To identify specific CNTNAP2 SNPs associated with white matter tract integrity in healthy controls and schizophrenia patients.

Main Methods:

  • Diffusion Tensor Imaging (DTI) was performed on 81 healthy controls and 44 schizophrenia patients.
  • Genotyping was conducted for 31 single nucleotide polymorphisms (SNPs) within the CNTNAP2 gene.
  • Tract-based Spatial Statistics (TBSS) and Analyses of Covariance (ANCOVAs) were used to analyze genotype-DTI associations.

Main Results:

  • A significant association was found between the rs2710126 genotype and Fractional Anisotropy (FA) in the uncinate fasciculus (p = .00003) after Bonferroni correction.
  • This finding remained significant despite rigorous statistical correction.
  • Several other nominally significant genotype-DTI associations were observed but did not survive correction.

Conclusions:

  • The study provides novel evidence linking CNTNAP2 genetic variants to specific white matter tract integrity.
  • The rs2710126 variant's association with the uncinate fasciculus highlights a potential genetic contribution to brain connectivity alterations in schizophrenia.
  • These findings contribute to understanding the genetic underpinnings of brain connectivity disruptions in schizophrenia pathophysiology.