Table 3.

Summary of studies from Systematic Review 2 (SR2).

Authors (year); PubMed ID	Sample	Measure(s) of adrenarche	Measure(s) of brain structure or function	Summary of findings
Murray et al. (2016) PMID: 26600008	100 children who completed an MRI scan, out of 128 9-year-old children, selected based on high vs. low DHEA and testosterone levels in saliva 6 months prior	Continuous levels of DHEA, DHEA-S, and testosterone were measured again in saliva (averaged across 2 mornings); Tanner stage based on parent-report Sexual Maturity Status line drawings	Structural MRI to measure pituitary gland.	Pituitary volume was positively associated with levels of DHEA (r = 0.28, p < 0.01), DHEA-S (r = 0.32, p < 0.01), and testosterone (r = 0.24, p < 0.05). Note: Associations between adrenarche and anxiety symptoms were also found, reported in SR1.
Whittle et al. (2015) PMID: 25678548	83 children who completed an fMRI task, out of 128 9-year-old children, selected based on high vs. low DHEA and testosterone levels in saliva 6 months prior	Continuous levels of DHEA were measured again in saliva (averaged across 2 mornings); Tanner stage (nuisance factor) based on parent-report Sexual Maturity Status line drawings	fMRI during an emotional face-viewing task. ROIs: amygdala, hippocampus, cingulate cortex, insula, dlPFC, and striatum	Levels of DHEA were negatively associated with activity in the right insula and mid-cingulate cortex during fear compared to calm faces, in the right mid-cingulate during angry compared to calm faces, and in the left dorsal cingulate during happy compared to calm faces. For females, these associations were present in the insula, cingulate, and dlPFC for fear faces, right mid-cingulate and putamen for angry faces, and insula and right cingulate for happy faces. Females also had a positive association between DHEA and activity in the left subgenual and right vmPFC for happy faces. No associations for males. Note: Associations between adrenarche and mental health symptoms were also found, reported in SR1.
Klauser et al. (2015) PMID: 25459897	41 early developing (mean age 9.64 ± 0.35) and 44 late developing (9.48 ± 0.30) children based on DHEA and testosterone levels	Early vs. late adrenarche based on levels of DHEA and Testosterone approximately 6 months earlier; Continuous levels of DHEA and testosterone were measured again in saliva (averaged across 2 mornings); Tanner stage based on parent-report Sexual Maturity Status line drawings	Structural MRI to measure gray and white matter volume	Controlled for age, and for Tanner stage to exclude effect of early gonadarche. No group differences in total brain volume, total gray matter volume, total white matter volume, or regional gray matter volume in the whole sample, or for boys and girls separately. The early group had decreased white matter volume on left anterior corona radiata (frontal lobe) for the whole sample (peak t = 4.21, corrected p = 0.046), and in a subsample of males (peak t = 4.43, corrected p = 0.019), but not females. Current DHEA levels were also negatively correlated with white matter volume in left corona radiata in the whole sample (peak t = 3.98, corrected p = 0.022).
Menzies et al. (2015) PMID: 25454416	61 boys aged 12.7–16.0 years	Levels of DHEA (as well as testosterone and estradiol) in saliva (for post hoc analyses). Authors also grouped boys into early-mid puberty (gonadarche) and late-post puberty via Tanner stage (for a priori analyses).	White matter microstructure (DTI): white matter mean diffusivity (MD) and fractional anisotropy (FA)	There were no associations between FA and gonadarche status based on Tanner stage, so no post hoc analyses were conducted for FA. For MD, there were no significant associations with DHEA (but there was a significant negative association with testosterone)
Nguyen et al. (2013) PMID: 23804104	Longitudinal study of 255 healthy children from 4 to 22 years old (143 females, 112 males)	Levels DHEA (and testosterone for 234 participants) measured in saliva over the course of 4 years at each MRI visit; Self-report PDS used to differentiate between pre- and post-gonadarche participants	Repeated MRI scans every 2 years – measured cortical thickness (CTh).	DHEA associated with increased CTh in left frontal, right temporal, and right parietal lobes in the pre-gonadarche group (r = 0.15). No significant DHEA-CTh associations in the post-gonadarche group. Age analysis showed DHEA associated with increased CTh between 4–13 years (all rs = 0.2): in the DLPFC from 4 to 8, right premotor cortex from 5 to 11, right temporoparietal junction from 7 to 12, and right entorhineal/perirhinal cortex from 4 to 13. After age 13, no significant associations. In the complete sample, significant interaction between DHEA and testosterone for the right ACC (r = 0.2). In the pre-gonadarche group, significant interaction between DHEA and testosterone in the right posterior cingulate gyrus and occipital pole (r = 0.3 for both). No significant interaction between DHEA and testosterone in the post-gonadarche group. No interactions with sex.
Klapwijk et al. (2013) PMID: 23998674	35 female adolescents aged 11.1–13.7 years (mean 12.6; SD 0.7), 33 of which also had DHEA measured in saliva	Levels of DHEA in saliva (as well as testosterone and estradiol). Other separate indicators of puberty were Tanner stages and self-reported menarcheal status, and the latter two were combined to create early and late groups.	fMRI during an emotion evocation task (two social and two basic emotions); functional connectivity between the dmPFC and other social brain regions (pSTS, TPJ and ATC)	No associations between DHEA and functional connectivity.
Goddings et al. (2012) PMID: 23106734	42 female adolescents mean age 12.5 years, range 11.1–13.7 years.	This study did not measure adrenarche specifically (early/late pubertal groups were based on Tanner stages and menarche – likely measures of pre/post gonadarche, especially in the age range of the sample), but they did measure salivary levels of testosterone, estradiol, and DHEA. Results are shown for DHEA associations only.	fMRI during emotional evocation (social vs. basic emotions). ROIs: MPFC, precuneus, right pSTS/TPJ, left ATC, left DMPFC.	Levels of DHEA positively associated with activity in the left anterior temporal cortex (ATC) during the social emotion tasks compared to the basic emotion tasks.