Sex-specific associations between subcortical morphometry in childhood and adult alcohol consumption: A 17-year follow-up study

Abstract

Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.

Trial registration: ClinicalTrials.gov NCT00001246.

Keywords: Alcohol; Amygdala; Hippocampus; Longitudinal predictors; Sex differences; Subcortical anatomy.

Copyright © 2021. Published by Elsevier Inc.

Figures

Fig. 1

Visual representation of participants’ study enrollment and peak drinking. Color encodes sex (red = female / blue = male). Line segments span baseline and follow-up visits. Points along the lines represent the time point of peak drinking, with the size of these points representing the average drinks per month. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Sex-specific relationships between amygdalohippocampal anatomy in childhood and alcohol consumption in adulthood. (A) Size of the amygdala and hippocampus in childhood (age-and-sex-regressed total bilateral volume) show a sex-biased relationship with alcohol use in adulthood (drinks per month during period of greatest use). There is a robust Sex*Drinks interaction (solid-colored lines, sex interaction p < 0.05) driven by a statistically-significant negative association between volume and surface area in childhood and alcohol use in adulthood for females (red, amygdala: b = −5.2, p = 0.006/hippocampus: b = −2.6, p = 0.01), which is absent in males (blue, p’s > 0.4). This interaction holds when excluding the three males consuming > 150 drinks per month in adulthood (dashed black lines). (B) Center panel: surface vertex maps showing those subregions of each structure which display the statistically-significant Sex*Drinks interaction for local surface area (middle image: rostral view of amygdala and hippocampus / upper image: rostroventral view of amygdalar focus / lower image: rostrocaudal view of hippocampal focus. Neighboring scatterplots show the underlying data with age and sex residualized at each focus of interaction. All foci show a female-specific relationship between local surface area in childhood and alcohol consumption in adulthood. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)