A tale of two steroids: The importance of the androgens DHEA and DHEAS for early neurodevelopment

Greaves, Ronda F.; Wudy, Stefan A.; Badoer, Emilio; Zacharin, Margaret; Hirst, Jonathan J.; Quinn, Tracey; Walker, David W.

doi:10.1016/j.jsbmb.2018.12.007

Cited by 36 publications

(32 citation statements)

References 113 publications

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“…Increased circulating DHEAS levels have been linked to improved brain plasticity during growth and maturation [16,3]. Some earlier studies have found a positive association between salivary DHEA levels measured before a cognitive task and working memory in young women [44].…”

Section: Discussionmentioning

confidence: 99%

“…Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are abundant steroid hormones and androgen precursors produced by adrenal cortex. DHEAS has been suggested as an important neurosteroid that promotes neuroneogenesis, neuronal growth, and neuronal survival by its antioxidative, anti-inflammatory, and antiglucocorticoid effects [1,2,3]. Serum DHEAS levels have been positively correlated with global cognition, working memory, attention, and verbal fluency in some studies among adults [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…However, prepubertal girls with premature adrenarche had no differences in cognitive measures such as intelligence quotient (IQ) and executive functioning compared to on-time girls [15]. It has also been suggested that an increased concentration of DHEA at around seven years of age enables maintaining synaptic plasticity [16,3] with a prolonged development of the cortex, particularly in the insula, thalamus, and anterior cingulate [16], structures that integrate somatosensory, homeostatic, and emotional information [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…Androgens may play an important role in cortical maturation and cognitive development during midchildhood [10,11,12,3]. However, little is known about the association between adrenarche and cognition in general populations of children.…”

Section: Introductionmentioning

confidence: 99%

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Associations of IGF-1 and Adrenal Androgens with Cognition in Childhood

et al. 2019

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Background: Little is known about the association between adrenarche and cognition in general populations of children. We therefore studied the associations of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone, insulin-like growth factor-1 (IGF-1), and adrenarche with cognition among prepubertal children. Methods: These cross-sectional analyses are based on baseline data of the Physical Activity and Nutrition in Children Study. A total of 387 children (183 girls, 204 boys) were included in the analyses. Raven’s Coloured Progressive Matrices (CPM) score was used to assess nonverbal reasoning. Serum adrenal androgens and IGF-1 concentrations were measured and clinical signs of androgen action were evaluated. Results: Higher IGF-1 among boys (β = 0.149, p =0.033) was related to a better Raven’s CPM score after adjustment for age and parental education. Adrenal androgens in girls or boys or IGF-1 in girls were not associated with the score. There were no differences in Raven’s CPM score between children with biochemical adrenarche (DHEAS ≥1.08 µmol/L; ≥40 µg/dL) or with clinical signs of androgen action and children without them. Conclusion: The results suggest that higher serum IGF-1 among boys is related to better cognition in prepubertal children. We could not provide evidence for the associations of adrenal maturation with cognition in prepubertal children.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Associations of IGF-1 and Adrenal Androgens with Cognition in Childhood

et al. 2019

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“…Thus, current results beg the question of what is evolutionarily novel and adaptive about the high and increasing level of circulating DHEAS in humans at the onset of middle childhood around 6-7 years. 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.…”

Section: Introductionmentioning

confidence: 90%

DHEAS and Human Development: An Evolutionary Perspective

Campbell

2020

Front. Endocrinol.

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Adrenarche, the post-natal rise of DHEA and DHEAS, is unique to humans and the African Apes. Recent findings have linked DHEA in humans to the development of the left dorsolateral prefrontal cortex (LDPFC) between the ages of 4-8 years and the right temporoparietal junction (rTPJ) from 7 to 12 years of age. Given the association of the LDLPFC with the 5-to-8 transition and the rTPJ with mentalizing during middle childhood DHEA may have played an important role in the evolution of the human brain. I argue that increasing protein in the diet over the course of human evolution not only increased levels of DHEAS, but linked meat consumption with brain development during the important 5-to-8 transition. Consumption of animal protein has been associated with IGF-1, implicated in the development of the adrenal zona reticularis (ZR), the site of DHEAS production. In humans and chimps, the zona reticularis emerges at 3-4 years, along with the onset of DHEA/S production. For chimps this coincides with weaning and peak synaptogenesis. Among humans, weaning is completed around 2 ½ years, while synaptogenesis peaks around 5 years. Thus, in chimpanzees, early cortical maturation is tied to the mother; in humans it may be associated with post-weaning provisioning by others. I call for further research on adrenarche among the African apes as a critical comparison to humans. I also suggest research in subsistence populations to establish the role of nutrition and energetics in the timing of adrenarche and the onset of middle childhood.

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