Abstract
Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.
Highlights
The burden of alcohol dependence to society is substantial, with an estimated global annual economic impact of between 210 and 665 billion US dollars arising from health consequences, workplace issues, safety, drinkdriving, and criminal costs[1,2]
Given the opportunities afforded by the large sample of this study, we explored group and group-by-sex differences in additional amygdala nuclei and hippocampal subfields (i.e., CA4, hippocampal-amygdaloid transition area, fimbria, fissure, tail, presubiculum, and parasubiculum)
Our key findings were that males with alcohol dependence had dosedependent smaller volumes of the basolateral amygdala nucleus, and smaller volumes in exploratory subregions of the amygdala and hippocampus
Summary
The burden of alcohol dependence to society is substantial, with an estimated global annual economic impact of between 210 and 665 billion US dollars arising from health consequences, workplace issues, safety, drinkdriving, and criminal costs[1,2]. Alcohol dependence is more common in men than in women[3]. The impact of alcohol dependence on women is problematic. There is a knowledge gap in the evidence informing such theories as they are largely biased by the inclusion of male-only samples, and three-quarters of published studies have failed to evaluate the interaction between alcohol dependence and sex[10,11]. New evidence on sex differences within the neurobiology of alcohol dependence is required to advance existing neuroscientific theories of addiction, clarify the role of sex in the mechanisms of substance use disorders, contribute to the design of gender-tailored treatments, and inform personalised medicine
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