Biology subjects

Williamson, D. E.

Publications and source records attributed to Williamson, D. E..

3 recordsLinked to original sources

bioRxiv2018

Convergent evidence for predispositonal effects of brain volume on alcohol consumption

BackgroundAlcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors and/or causal consequences of alcohol use remains poorly understood.\n\nMethodsData came from 3 neuroimaging samples (total n=2,423), spanning childhood/adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use, and/or a causal consequence of alcohol use. Finally, we evaluated whether GWAS-defined genomic risk for alcohol consumption is enriched for genes preferentially expressed in regions identified in our neuroimaging analyses, using heritability and gene-set enrichment, and transcriptome-wide association study (TWAS) approaches.\n\nResultsSmaller right dorsolateral prefrontal cortex (DLPFC; i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene-sets preferentially expressed in the DLPFC and associated with differential expression of C16orf93, CWF19L1, and C18orf8 in the DLPFC.\n\nConclusionsThese data suggest that smaller DLPFC and insula GMV plausibly represent predispositional risk factors for, as opposed to consequences of, alcohol use. Alcohol use, particularly when heavy, may potentiate these predispositional risk factors. DLPFC and insula GMV represent promising biomarkers for alcohol consumption liability and related psychiatric and behavioral phenotypes.

neuroscience↗

bioRxiv2017

Trajectories of Alcohol Use Initiation and Risk to Develop an Alcohol Use Disorder During Adolescence: A Role for Stress and Amygdala Activity

Early alcohol use initiation predicts onset of alcohol use disorders (AUD) in adulthood. However, little is known about developmental trajectories of alcohol use initiation or their putative biological and environmental correlates. Here we report the results of latent class analyses identifying two trajectories of alcohol use initiation in a prospective study of adolescents selected for the presence or absence of familial risk for depression at baseline. The latent class analyses identified two distinct patterns of initiation: early initiators (EI; n=32) who reported greater baseline alcohol use (M = 1.12, SE = .35) and exhibited a more rapid rate of change in use between baseline and each follow up wave (M = 4.43, SE = .94); and in contrast, late initiators (LI; n=298) who reported lower baseline use (M = .23, SE = .03) and exhibited a slower rate of change between baseline and each of the subsequent follow up waves (M = .12, SE = .03). Early initiators had more positive expectancies regarding alcohol (p = .002 - p = .005) and reported higher levels of stressful life events during the year prior to baseline assessment (p = .001). Additionally, fMRI analyses revealed that EI displayed heightened threat-related amygdala activity at baseline compared to LI (p = .001), but no differences in reward-related ventral striatum activity. Lastly survival analyses revealed that EI initiators were 6.7 times more likely to develop an AUD by age 19 when compared to the LI (p = .005). These patterns, which were independent of broad familial risk for depression, suggest that early initiation of alcohol use during adolescence associated with later risk for AUD is reflected in both higher levels of stressful life events and higher neural reactivity to threat, the combination of which may inform ongoing efforts to prevent persistent dysfunction.

neuroscience↗

bioRxiv2017

Paradoxical Associations Between Higher Familial Warmth, Lower Stress, And Increased Amygdala Reactivity To Interpersonal Threat

Studies of early life extremes such as trauma, abuse, and neglect highlight the critical importance of quality caregiving in the development of brain circuits supporting emotional behavior and mental health. The impact of normative variability in caregiving on such biobehavioral processes, however, is poorly understood. Here, we provide initial evidence that even subtle variability in normative caregiving shapes threat-related brain function and, potentially, associated psychopathology in adolescence. Specifically, we report that greater familial affective responsiveness is associated with heightened amygdala reactivity to interpersonal threat, particularly in adolescents having experienced relatively low recent stress. These findings extend the literature on the effects of caregiving extremes on brain function to subtle, normative variability, but suggest that presumably protective factors may be associated with increased risk-related amygdala reactivity. We consider these paradoxical associations with regard to studies of basic associative threat learning and further consider their relevance for understanding potential effects of caregiving on psychological development.

neuroscience↗