Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Abstract

Although dehydroepiandrosterone (DHEA) may exert neuroprotective effects in the developing brain, prolonged or excessive elevations in cortisol may exert neurotoxic effects. The ratio between DHEA and cortisol (DC ratio) has been linked to internalising and externalising disorders, as well as cognitive performance, supporting the clinical relevance of this hormonal ratio during development. However, the brain mechanisms by which these effects may be mediated have not yet been identified.Furthermore, although there is evidence that the effects of cortisol in the central nervous system may be sexually dimorphic in humans, the opposite is true for DHEA, with human studies showing no sex-specific associations in cortical thickness, cortico-amygdalar or cortico-hippocampal structural covariance. Therefore, it remains unclear whether sex moderates the developmental associations between DC ratio, brain structure, cognition and behaviour. In the present study, we examined the associations between DC ratio, structural covariance of the hippocampus with

Role of testosterone: cortisol ratio in age- and sex-specific cortico-hippocampal development and cognitive performance

“…Further, the indirect effects of TC ratio on cognition through structural covariance only affect spatial span, not shifting abilities. Interestingly, we have also shown sex-specific associations between ACC-hippocampal covariance and the ratio between dehydroepiandrosterone (DHEA) and cortisol, 15 as well as cognitive benefits of DHEA:cortisol ratio in both boys and girls. 43 In comparison with estradiol -a metabolite of testosterone, DHEA is a precursor hormone for testosterone, i.e.…”

“…54 These results provide further evidence that the polymorphic effects of testosterone on cognition are composed of both direct (activation of androgen receptors and effects on cortico-hippocampal development) and indirect effects (conversion to estradiol, activation of estradiol receptors, and effects on cortico-amydalar development). 12,15,43,54 We also document sex-specific contributions of TC ratio to prefrontal-hippocampal development. However, sex differences in brain structure as a function of TC ratio did not result in sex differences in cognition in our study.…”

“…Studies have found significant associations of cortico-hippocampal structural covariance with levels of adrenal and gonadal hormones in typically developing children, adolescents, and young adults. 12,15 Sex-specific associations were also revealed when examining testosterone-related covariance of prefrontal-hippocampal areas, which predicted lower executive function in boys, but not girls. 12 Hence, structural covariance may be sensitive enough to index both differences in TC ratio and in cognitive performance.…”

DHEAS and Human Development: An Evolutionary Perspective

“…I suggested that the primary effect (among others) of increasing DHEAS is the maintenance of plasticity in the developing brain (36,37), a point since elaborated by others (38,39). Recent finding showing an impact of DHEA on cortical development and cortical-limbic connectivity in children (14)(15)(16)(40)(41)(42)(43) provide strong support for this argument.…”

“…To be convincing arguments about the evolution of unique human traits like mentalizing (148) or the emergence of a novel life stage like middle childhood (55) require both a physiological substrate and evidence for a phylogenetic precursor. The onset of DHEAS production during early childhood (119,120), and its impact on brain development during both early and middle childhood (14,42,43), together with the emergence of mentalizing from 9 to 11 years (147) fits both criteria. Adrenarche is a physiological process with neurological consequences related to behaviors during middle childhood, and the increase in DHEAS is linked to the development of the adrenal ZR.…”