Family history of alcohol use disorder is associated with brain structural and functional changes in healthy first-degree relatives

Abstract

Background: Neuroimaging studies of vulnerability to Alcohol Use Disorder (AUD) have identified structural and functional variations which might reflect inheritable features in alcohol-naïve relatives of AUD individuals (FH+) compared to controls having no such family history (FH-). However, prior research did not simultaneously account for childhood maltreatment, any clinically significant disorder and maternal AUD. Therefore, we mainly aimed to investigate the brain structure and reward-related neural activations (fMRI), using whole-brain analysis in FH+ young adults with no prevalent confounders. Methods: 46 FH+ and 45 FH- male and female participants had no severe childhood maltreatment exposure, neither any psychiatric disorder or AUD, nor a prenatal exposure to maternal AUD. We used a 3 T MRI coupled with a whole brain voxel-based method to compare between groups the grey matter volumes and activations in response to big versus small wins during a Monetary Incentive Delay task. The Childhood Trauma Questionnaire score was used as confounding variable in the analyses to account for the remaining variance between groups. Results: Compared to FH- controls, FH+ participants had smaller grey matter volumes in the frontal and cingulate regions as well as in the bilateral nucleus accumbens and right insula. The FH+ participants’ fMRI datasets denoted a blunted activation in the middle cingulum with respect to FH- controls’ during the processing of reward magnitude, and a greater activation in the anterior cingulum in response to anticipation of a small win. Conclusions: Family history of alcohol use disorder is linked to structural and functional variations including brain regions involved in reward processes.

Reward Processing in Alcohol-Dependent Patients and First-Degree Relatives: Functional Brain Activity During Anticipation of Monetary Gains and Losses

“…We found no significant functional differences between FH 1 and FH 2 subjects in VTA, VS, ACC, or AI during gain anticipation. While this is in line with a number of previous studies (46)(47)(48)(49), it stands in contrast to others reporting functional differences of inconsistent direction between FH 1 and FH 2 subjects during gain anticipation (45,(50)(51)(52).…”

“…For instance, according to the reward deficiency syndrome hypothesis (26), FH 1 subjects, and (abstinent) individuals with alcohol dependence should exhibit similarly decreased neural activation to non-substance-related rewards, resulting in a chronic dysphoric state that can solely be reversed by substance use or other highly rewarding activities (26). While most MIDT studies in FH 1 subjects (46)(47)(48)(49) found no functional differences to healthy subjects during the anticipation phase, other studies showed comparatively increased (45,50,51) or decreased (52) activity in relatives. Differences existed in the VS, ACC, and insula, among others (45,51,52).…”

The effect of alcohol withdrawal syndrome severity on sleep, brain and cognition

“…The frontal lobes being particularly rich in glutamatergic pathways ( Kril et al , 1997 ), they are likely to be especially vulnerable to the severity of AWS. However, we do not exclude that these brain alterations may have been present before alcohol cessation because of the effects of chronic and heavy alcohol consumption or a family history of AUD or comorbidities such as liver disease or thiamine deficiency ( Harper, 2009 ; Chen et al , 2012 ; Filippi et al , 2019 ). In this case, altered brain structure would constitute a vulnerability factor for exhibiting more severe AWS.…”

Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder

“…These large-scale studies highlight cross-sectional differences whereas prospective studies and comparisons with unaffected family members point towards potential trait related effects. Healthy subjects with a positive family history, show reduced volumes within prefrontal cortices (middle and inferior frontal and orbitofrontal gyrus), mid-cingulate, right insula and bilateral nucleus accumbens (Filippi et al, 2019) and the right parahippocampal gyrus (Sjoerds et al, 2013b). In adolescents with limited alcohol exposure, a positive family history was associated with lower cortical thickness in orbitofrontal and superior parietal cortices in additional to greater impulsivity and impaired memory (Henderson et al, 2018).…”