Assessment of whole brain white matter integrity in youths and young adults with a family history of substance‐use disorders

Abstract

Individuals with a family history of substance use disorders (FH+) are at a greater risk of developing substance use disorders than their peers with no such family histories (FH−) and this vulnerability is proportional to the number of affected relatives (FH density). The risk for developing substance use disorders peaks during adolescence to early adulthood in the general population, and that is thought to be related to delayed maturation of frontocortical and frontostriatal functional circuits. We hypothesized that FH+ youth and young adults have impaired myelination of frontocortical and frontostriatal white matter tracts. We examined fractional anisotropy (FA) data in 80 FH+ and 34 FH− youths (12.9±1.0 years) and in 25 FH+ and 30 FH− young adults (24.3±3.4 years). FH+ youths had lower FA values in both frontocortical and frontostriatal tracts as well as parietocortical tracts including the anterior, superior and posterior corona radiata and the superior frontal-occipital fasciculus. Moreover, FA values in these tracts were negatively correlated with FH density. FH+ adults had lower FA values in two frontocortical tracts: the genu of the corpus callosum and anterior corona radiata and also significant negative correlations between FA and FH density in these same tracts. In both groups, lower FA values corresponded to higher radial diffusivity suggesting reduced axonal myelination. We interpreted our findings as evidence for impaired myelination of frontal white matter that was proportional to FH density. Our data suggest that deficits may partially resolve with age, paralleling an age-related decline in risk for developing substance use disorders.

Increased Forebrain Activations in Youths with Family Histories of Alcohol and Other Substance Use Disorders Performing a Go/NoGo Task

“…Overall, our findings suggest that global activation increases in FH+ youths are modulated by FH density and not specific to the inhibitory components of the task. This pattern of increased activations in FH+ youths may be at least partially due to impaired forebrain white matter development (Herting et al, 2010, Acheson et al, 2014b, Acheson et al, 2014a) leading to greater activations as a result of less efficient neural communication during task performance.…”

“…The increased forebrain activations in FH+ youths may be due at least in part to their impaired forebrain white matter integrity (Herting et al, 2010, Acheson et al, 2014b, Acheson et al, 2014a) as decreased forebrain white matter integrity has previously been associated with increased forebrain activations during task performance and is thought to indicate increased energy required due to poorer insulation of axonal tracts resulting in decreased neural efficiency (Burzynska et al, 2013, Zhu et al, 2013). Specifically, improved white matter integrity increases the efficiency of neuronal firing by reducing ion leak through axonal membranes and shifting some of the metabolic burden of action potential propagation from neurons to oligodendrocytes and other glial cells by facilitating saltatory conduction.…”

“…We have previously reported that these FH+ youths have impaired white matter integrity (Acheson et al, 2014a, Acheson et al, 2014b). We used a block design go/no go task and examined effects of FH status on activations in blocks with only go trials, blocks with 50% go and 50% no go trials, and a contrast of those 2 conditions.…”

“…This risk is thought to be driven by behavioral and cognitive characteristics of “behavioral undercontrol” or “neurobehavioral disinhibition” consisting of increased sensation seeking and antisocial behaviors as well as deficits in executive functioning, impulse control, decision making, and attention (e.g., Stevens et al, 2003, Deckel, 1999, Corral et al, 2003, Acheson et al, 2011a, Acheson et al, 2011b, Lovallo et al, 2006, Tarter et al, 2003, Sher et al, 2004, Sher and Trull, 1994). Further, this increased risk may be at least partially driven by impaired or altered development of forebrain circuitry as FH+ youths and young adults appear to have impaired frontal white matter development (Herting et al, 2010, Acheson et al, 2014b, Acheson et al, 2014a) and show evidence of altered forebrain activity at both rest and while performing cognitive tasks (e.g., Schweinsburg et al, 2004, Acheson et al, 2009, Silveri et al, 2011, Heitzeg et al, 2010, Cservenka et al, 2012, Spadoni et al, 2008). However, it is not fully understood how forebrain activity is altered in FH+ individuals and ultimately how these alterations may contribute to substance use disorder risk.…”

“…While interesting and important, these studies did not compare overall activations in FH+ and FH− individuals across all task conditions while performing the task. Given that reduced cerebral myelination is associated with increased BOLD activations (Burzynska et al, 2013, Zhu et al, 2013), FH+ youths may be expected to show increased forebrain activations generally while performing go/no go tasks since they appear to have forebrain white matter impairments (Herting et al, 2010, Acheson et al, 2014b, Acheson et al, 2014a). This is an important distinction as it would suggest more basic differences in FH+ individuals such as more globally decreased forebrain neural efficiency in FH+ individuals rather than differences limited to inhibitory circuitry functioning.…”