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

Abstract

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.

Figure 1

Relationships of FH density (number of parents and grandparents with substance use disorders) to anterior corona radiata (ACR) fractional anisotropy (FA) (P < 0.0001; top panel), N‐acetylaspartate (NAA) (P = 0.035; middle panel), and total choline (tCho) (P < 0.0001; bottom panel).

Figure 2

Schematic representation of proposed mechanisms underlying lower white matter integrity in FH+ individuals. Reduced NAA concentrations underlie impaired synthesis/maintenance of axonal myelin and consequently elevated diffusivity across the axonal membrane (Dr). Reduced NAA also leads to increased membrane turn over and elevation of tCho compounds in glial cells.