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Exploring the relationship between white matter integrity, cocaine use and GAD polymorphisms using Bayesian Model

Tmader Alballa1,2, Edward L Boone1,3, Liangsuo Ma4,3

  • 1Department of Statistical Sciences and Operations Research, Virginia Commonwealth University, Richmond, Virginia, United States of America.

Plos One
|July 26, 2021
PubMed
Summary

Genetic variations in glutamic acid decarboxylase (GAD) may influence white matter changes in individuals with cocaine use disorder (CUD). Specific GAD polymorphisms show distinct associations with brain alterations and chronic cocaine use.

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Area of Science:

  • Neuroimaging
  • Genetics
  • Addiction Research

Background:

  • Cocaine use disorder (CUD) is associated with white matter abnormalities, particularly in the corpus callosum.
  • Glutamic acid decarboxylase (GAD) plays a crucial role in neurotransmission and has been implicated in various neurological conditions.

Purpose of the Study:

  • To investigate the relationship between GAD gene polymorphisms and white matter changes in individuals with CUD.
  • To explore the interactive effects of GAD1a and GAD1b polymorphisms with years of cocaine use (YCU) on brain structure.

Main Methods:

  • Diffusion tensor imaging (DTI) was used to assess white matter integrity.
  • Bayesian model averaging with multiple linear regression was applied to analyze DTI data in conjunction with genetic polymorphisms and YCU.
  • Two-way and three-way interactions between GAD1a (rs1978340), GAD1b (rs769390), and YCU were examined.

Main Results:

  • GAD1a polymorphism was linked to frontal white matter alterations independently.
  • GAD1b polymorphism was associated with midbrain, cerebellar changes, and exacerbated white matter changes with chronic cocaine use.
  • The three-way interaction (GAD1a|GAD1b|YCU) suggested potential protective effects in the corpus callosum and cerebellar peduncle, indicated by fewer voxel changes.

Conclusions:

  • GAD polymorphisms may modulate the impact of CUD on white matter integrity.
  • Specific GAD variants exhibit differential effects on brain structure in the context of cocaine use.
  • Combined GAD polymorphisms might offer a degree of neuroprotection in specific brain regions affected by chronic cocaine exposure.