Historically, sexor gender-related differences in addictions have been understudied. When neglected, both sexes may not receive the full benefit of medical research. Although hormone fluctuations in women are rarely investigated with respect to treatments, levels of estrogen and progesterone may have large impacts on the efficacies of behavioral or pharmaceutical interventions (1–7). The National Institutes of Health (NIH) have been advocating for investigating gender-related differences and hormonal influences (8), including with respect to impulse control and its contributions to addictions. Despite the importance of studying sex differences, the standard integration of sex-difference considerations, including in preclinical research using cell lines and animals, has yet to occur. Sex differences are present in personality traits and behaviors, such as impulsivity, that have been associated with addictions (both substance and non-substance). Impulsivity has been defined as a tendency to act with little foresight or little consideration of future consequences (9, 10). Impulsivity is a complex construct that may be separated into specific factors; two main domains that can be measured in the laboratory include impulsive action and impulsive choice (11). Both impulsive action and choice have been associated with drug use, in both a predictive fashion and as a result of drug use (12, 13). Work investigating sex differences in impulsive action in both animals and humans has shown mixed results (14). The mixed findings may in part relate to sex hormones, with females displaying fluctuating levels of impulsivity dependent on cycle phase and estrogen levels (14). Impulsive choice has been measured in the laboratory using delay-discounting tasks (13, 15–17). While multiple studies suggest that men may be more impulsive than women, careful investigation of specific facets suggest otherwise. Women may display greater discounting rates than men (i.e., greater choice impulsivity); however, reward type is relevant as men have been found to discount real money more rapidly than women, with women discounting hypothetical rewards more rapidly than men (18). Among adolescents, female smokers appear more impulsive than male smokers, but male control subjects appear more impulsive than female control subjects (19). Consistent with findings from Kirby and Marakovic (18); Heyman and Gibb (20) found that female smokers also tend to discount the value of hypothetical rewards more rapidly than do males. Among heavy drinkers, women exhibit poorer inhibitory control than men (21, 22). A study investigating the neural correlates of impulsivity in non-abusing individuals who were family-history positive for alcohol abuse found that those who are family-history positive show greater recruitment of brain regions involved in addiction, inhibitory control, and executive function compared to those without family histories of alcoholism; however, this effect was driven by males (23). Had gender differences not been built into the experimental design, such a finding would not have been identified. Although there exist strong associations between drug use and impulsivity in both humans and animals, with impulsivity increasing the propensity for drug use and vice-versa (12, 13, 24, 25), few studies have investigated sex differences, particularly in preclinical work. The possible roles for cycle phase or circulating hormones in delay-discounting-task performance warrant further study. Impulsivity and behavioral performance in impulsivity tasks does not always differ between men and women; however, that does not mean that both sexes are achieving similar performance in the same way. Even when men and women perform comparably in inhibitory tasks, different neurobiologies may underlie the behaviors. For example, in a recent study of genderrelated differences in neural factors associated with performance of the stop-signal task, men tended to show more activation in the lentiform nucleus, parahippocampal gyrus, posterior and anterior cingulate cortices, middle and medial frontal cortices, and thalamus, compared to women, despite similar performance on the task (26). In general, men and women display different brain connectivity patterns, both in adolescence and adulthood. One study found that men show greater within-hemispheric connectivity and women show greater acrosshemispheric activity, suggesting that male brains may be better suited to facilitate connectivity between perception and coordinated action, whereas female brains may be better suited to facilitate communication between analytical and intuitive processes (27). As neurobiological differences in males and females start in early stages of development (28, 29), it may be difficult to
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Dec 25, 2024
Bingji Wang + 2
Open Access