Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

Hum Brain Mapp. 2014 Dec;35(12):5877-87. doi: 10.1002/hbm.22591. Epub 2014 Jul 21.


Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population's increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH- youths (12.9 ± 1.0 years old). White matter integrity indices included fractional anisotropy (FA), N-acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build-up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P < 0.0001) and NAA (P = 0.017) and higher tCho (P = 0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P < 0.0001) and NAA (P = 0.011) and positively correlated with tCho (P = 0.001). FA was independently predicted by both FH density (P = 0.006) and NAA (P = 0.002), and NAA and tCho were both independent predictors of FH density (P < 0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes.

Keywords: diffusion tensor imaging; family history; frontal white matter integrity; proton magnetic resonance spectroscopy; risk; substance use.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anisotropy
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / metabolism*
  • Brain / pathology*
  • Child
  • Choline / metabolism
  • Diffusion Tensor Imaging
  • Family
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Multimodal Imaging
  • Proton Magnetic Resonance Spectroscopy
  • Regression Analysis
  • Risk
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / pathology*
  • White Matter / metabolism*
  • White Matter / pathology*


  • Aspartic Acid
  • N-acetylaspartate
  • Choline