Offspring from families with alcohol dependence have been shown to exhibit brain morphological alterations that appear to be related to their familial/genetic risk for alcohol dependence. Greater susceptibility for developing alcohol dependence may be related to structural underpinnings.
Over the past 18 years we have been conducting magnetic resonance imaging (MRI) studies to look at brain structural differences between participants from families with a greater susceptibility of developing alcohol dependence and those from low-risk control families.
Starting in 2001 manual tracing techniques were used to identify regions of interest that might differ between children/adolescents and young adults from families with an alcohol dependence background and those from control families without such background.
Adolescents/young adults from families with multiple cases of alcohol dependence showed increased total cerebellum volume in comparison with control participants.
Normal development includes pruning of brain regions during adolescents, those with larger cerebellums may show a delay in pruning with age.
In 2013 Diffusion Tensor Imaging (DTI) was initiated to measure the integrity of the brains white matter tracks.
The interaction of personal exposure to alcohol and familial risk for alcohol dependence predicts reduction in White Matter integrity for the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF).
The SLF tract (illustrated in blue) is seen with clusters of voxels for our participants (red).
The effect of having a family history of alcohol dependence on brain volumes in young adults was assessed using voxel-based morphometry (VBM) and published in 2017. In this study, we thought it important to distinguish the effects of any prenatal use of substances that the mothers may have had that could affect their offspring versus effects that may have resulted from their familial-genetic predisposition to develop an alcohol use disorder or related substance use disorder. Our results showed several regional differences.
VBM analysis of 88 participants (36 High-Risk and 39 Low-Risk) that included gender, intracranial volume (ICV), personal history of substance use disorder and prenatal exposure to alcohol, cigarettes, and drugs revealed gray matter volume differences in the left fusiform, left insula, right lingual area, and in the cerebellum, lobes 8 and 9 (left) that survived family-wise error rate (FWE) correction.
Cortical Thickness Measures with FreeSurfer
Familial risk differences in amplitude of Event Related Potential (ERP) components have been demonstrated, some of these differences appear to change with development, most likely in association with maturation of brain structures. Cortical thickness is one measure of brain morphology that changes with development. Assessing multiple brain regions using FreeSurfer, we tested whether regional differences in cortical thickness map to specific event-related potential (ERP) measures. Our interest in doing this is based on numerous studies from our lab and others showing that one component of the ERP wave, the P300 component, shows reduced amplitude in those with a family history. Moreover, we found that although those with family history had smaller amplitude, with development they did not differ from the control children.
Cortical thickness has been shown to differ between offspring from families with and without a family history of alcohol dependence. Also, cortical thickness has been suggested to show developmental changes in a number of published studies, some suggesting that the developmental goal of the brain is to eventually show lesser thickness.
Among the significant associations with familial risk and ERP was cortical thickness of the pars opercularis and P300 amplitude in the right hemisphere, and the temporal pole and N250 in the left hemisphere.
Neural activity reflected in ERP amplitude is positively related to cortical thickness in regions found to differ by familial risk status and involved in impulsivity and decision-making.