Table 1.

Summary of studies from Systematic Review 1 (SR1).

Authors (year); PubMed ID	Sample	Measure(s) of adrenarche	Measure(s) of mental health	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)	Self-reported SCAS (anxiety symptoms)	SCAS scores were not significantly associated with hormone measures Note: Associations between adrenarche and brain structure were found, reported in SR2.
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 and testosterone were measured again in saliva (averaged across 2 mornings)	Parent-report CBCL (externalizing symptoms only), self-reported CDI (depressive symptoms), and self-reported SCAS (anxiety symptoms)	In females only, CBCL externalizing score was positively associated with DHEA (r = 0.364, p < 0.05). There were no significant associations between DHEA and mental health in males. Note: Associations between adrenarche and brain function were found, reported in SR2.
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; Tanner stage based on parent-report Sexual Maturity Status line drawings	Self-reported CDI (depressive symptoms) and self-reported SCAS (anxiety symptoms)	Controlled for Tanner stage to exclude effect of early gonadarche, and for age. No significant differences between early and late children were found for CDI or SCAS scores, for boys and girls together, or for boys or girls separately. Note: Associations between adrenarche and brain structure were also found, reported in SR2.
Belsky et al. (2015) PMID: 25915592	73 females in Grade 1 (aged 6.8–7.8 years, mean age = 7.25 years)	DHEA measured in saliva 4 times at home visit following Grade 1. Preadrenarcheal (41% of sample) = 6/8 assays below detection threshold of 10 pg/ml and all <16 pg/ml	At age 18 (mean age 17.84 yrs), self-report MacArthur Health and Behavior Questionnaire (internalizing and externalizing)	Longitudinal study found path for prenatal stress → maternal depression & negative parenting in infancy → increased cortisol at 4.5 yrs → accelerated adrenarcheal development → more physical and mental health problems age 18. Adrenarche & mental health correlated at 0.32 (p < = 0.01)
Mundy et al. (2015) PMID: 26592329	Population based study of 1124 children aged 8–9.	DHEA, DHEA-S, and testosterone measured in saliva. Hormone levels were standardized by age (separately by sex), then categorized into minimal, intermediate, and advanced development.	Parent-report Strengths and Difficulties Questionnaire (Difficulties scales: Emotional symptoms, conduct problems, hyperactivity/inattention, peer problems; Other scale: prosocial behavior)	In females, only higher levels of DHEA-S were positively associated with peer problems only. In males: higher levels of DHEA were associated with more peer problems and emotional symptoms; higher levels of DHEA-S were associated with more total difficulties, conduct problems, hyperactivity/inattention, and peer problems; higher levels of testosterone were associated with more total difficulties, peer problems, and emotional symptoms.
Sontag-Padilla et al. (2012) PMID: 22293005	76 girls mean age 7.50 years, SD = 0.85. Two groups: 40 with PA (recruited from pediatric endocrine clinics), 36 on time (recruited via community)	Premature adrenarche (PA) vs. on-time adrenarche. PA documented by a pediatric endocrinologist, Tanner 1 breast, Tanner 2 or greater pubic hair (On-time were Tanner 1 breast and Tanner 1 pubic hair). Adrenal hormones DHEA-S and androstendione were measured in serum to confirm PA status.	Parent report of the CBCL (internalizing and externalizing); Child self-report CDI (depressive symptoms), child self-report STAI-C (anxiety symptoms)	Main effects – PA girls had higher levels of CBCL internalizing scores [50.70 (10.45) vs. 46.06 (8.99), t = −2.01, d = 0.48, p < 0.05], and higher CBCL externalizing scores [50.28 (9.02) vs. 45.00 (8.67), t = −2.53, d = 0.60, <0.01] Interactions – PA interacted with: lower levels of executive functioning to predict higher externalizing and anxiety symptoms; increased cortisol to predict externalizing symptoms; and decreased cortisol to predict depressive symptoms
Dorn et al. (2008) PMID: 18655525	Same sample as Sontag-Padilla et al. (2012)	See Sontag-Padilla et al. (2012). This study also examined testosterone in blood	DISC (diagnostic interview); teacher and parent report CBCL (internalizing and externalizing); child self-report CDI (depressive symptoms), child self-report STAI-C (anxiety symptoms), child self-report relational aggression	Compared to on-time girls, PA girls had: − higher rate of diagnosis of ODD in the past year (20% vs 3.1%; p = 0.04), past month (17.5% vs 0%; p = 0.02), and lifetime (20% vs 3.1%; p = 0.04); − higher symptoms scores for separation anxiety (3.13 ± 2.43 vs. 1.77 ± 1.93), specific phobia (1.40 ± 1.13 vs. 0.59 ± 0.S4), GAD (3.08 ± 2.38 vs. 1.59 ± 1.74), panic disorder, OCD (0.48 ± 0.91 vs. 0.03 ± 0.18), MDD (4.93 ± 3.71 vs. 2.09 ± 1.91), ADHD (5.10 ± 4.87 vs. 2.59 ± 3.23), and ODD (6.45 ± 3.07 vs. 4.59 ± 3.10); − higher scores of parent-report Social Problems (55.2 ± 7.3 vs. 51.8 ± 4.6), Anxious/Depressed (54.2 ± 5.3 vs. 51.8 ± 3.4), Aggressive Behavior (54.0 ± 5.4 vs. 51.5 ± 3.2), total Externalizing Behavior (50.3 ± 9.0* 45.0 ± 8.7), total Internalizing Behavior (50.7 ± 10.5* 46.1 ± 9.0) and total Behavior Problems (50.0 ± 11.2** 4l.S ± 14.3) on the CBCL; − and higher scores of teacher-report aggressive behavior on the CBCL (p = 0.03)
Shirtcliff et al. (2007) PMID: 17537074	106 boys and 107 girls, mean age 13.7 years (SD = 1.7)	Continuous baseline levels (prior to a stress task) of DHEA in saliva (also measured pubertal development via Tanner stage)	Internalizing and externalizing symptoms with the parent- and child-report CBCL and DISC interview	Girls with more internalizing problems had lower levels of baseline DHEA. No significant associations between baseline DHEA and symptoms for boys.
Goodyer et al. (2000) PMID: 11102323	73 boys, 107 girls, mean age 13.5 years (range 12.2–16.5) at high risk for psychopathology (due to recent negative life events, high emotionality, or parental history)	DHEA in saliva at 08:00 and 20:00, averaged across 4 days, i.e., mean morning DHEA and mean evening DHEA.	Self-report depressive symptoms (Mood and Feelings Questionnaire); DSM-IV criteria for MDD with the K-SADS interview at a 12 month follow-up.	Mean DHEA (either morning or evening) did not predict if participants developed MDD at follow-up; however, associations between mean DHEA and self-report symptoms at baseline were not measured.
van Goozen et al. (2000) PMID: 11068901	3 groups of children, 24 with ODD, 42 psychiatric controls (PC), and 30 normal controls (NC; 16 boys), aged between 6 and 12 (ODD mean = 10.1, PC mean = 9.3, NC mean = 10.1).	DHEA-S measured in plamsa. Tanner stage measured for pubic hair and breast or male gential development	DSM-IV criteria via semistructured diagnostic interview for ODD and other psychiatric disorders	DHEA-S: Controlling for age and Tanner stage, there was a main effect of group [F (2,76) = 5.65, p < 0.01], with the ODD group having higher levels of DHEA-S (ODD = 3.01 μmol/L ± 1.7, PC = 1.63 ± 1.4, NC = 2.03 ± 1.1).
Dorn et al. (1999) PMID: 9988243	Pilot study of children 6–9 years old. 9 PA (8 girls, enrolled from pediatric endocrine clinics), 20 on-time (8 girls, recruited from the community).	Premature adrenarche (PA) vs. on-time adrenarche. PA documented by a pediatric endocrinologist, Tanner 2 or 3 pubic hair (On-time were Tanner 1 breast or genital and Tanner 1 pubic hair). Adrenal hormones DHEA, DHEA-S and delta-4-androstenedione were measured in serum and were higher in PA group.	Parent-report DISC interview for DSM-III disorders, parent-report CBCL, self-report CDI (depressive symptoms), and self-report STAI-C (anxiety symptoms)	PA children had higher CDI scores at the trend level only [10.2 ± 5.1 vs. 5.4 ± 5.1, t(24) = 2.03, p = 0.05]. PA children had higher scores on the parent-report CBCL for Somatic complaints (56.8 ± 8.5 vs. 51.4 ± 3.4, t = 2.42, p = 0.02), Withdrawal (56.9 ± 10.4 vs. 51.3 ± 3.9, t = 2.13, p = 0.04), Social Problems (54.9 ± 6.2 vs. 50.9 ± 2.6, t = 2.50, p = 0.02), total Internalizing (52.6 ± 13.5 vs. 42.5 ± 9.9, t = 2.20, p = 0.04), total Externalizing (54.1 ± 9.7 vs. 42.8 ± 9.6, t = 2.83, p = 0.01), and total Behavior Problems (53.5 ± 11.9 vs. 40.3 ± 10.7, t = 2.86, p = 0.01). 44% of children in the PA group had 1 or more diagnoses, while only 1 child in the on-time group had a diagnosis.
Van Goozen et al. (1998) PMID: 9474448	2 groups of boys, 15 with conduct or oppositional defiant disorder and 25 controls, aged 8–12 years (mean age CD: 10.2, controls: 9.6)	Androstenedione, testosterone, and DHEA-S measured in plasma	DSM-IV criteria for CD or ODD; Parent- and teacher-report CBCL (Aggression and Delinquency scales)	CD participants had a significantly higher level of DHEA-S [2.85 nmol/l ± 1.1 vs. 1.46 ± 0.8, F (1,38) = 22.68, p < 0.0001] and a higher level of androstenedione at trend level [1.03 ± 0.4 vs. 0.81 ± 0.3, F (1,38) = 3.82, p < 0.06], but no difference in testosterone [0.90 ± 1.1 vs. 0.86 ± 1.5, F (1,38) = 0.01, NS]. DHEA-S was significantly associated with parent-report Delinquency (rho = 0.33) and Aggression (rho = 0.46) and teacher-report Delinquency (rho = 0.39) and Aggression (rho = 0.48).
Goodyer et al. (1996)	3 groups of adolescents aged 8–16, 82 with MDD, 25 non-MDD psychiatric controls, and 40 healthy controls	DHEA in saliva, averaged over 2 days at 08:00, 12:00, and 20:00.	DSM-II criteria using the K-SADS diagnostic interview: 1) for MDD, 2) other psychiatric disorder, or 3) no disorder.	MDD group had lower morning DHEA than the other groups. No group differences in DHEA-S.
Susman et al. (1996) PMID: 8853589	108 healthy adolescents, 56 ten- to 15-year-old boys (mean age 12.7), 52 nine- to 15-year old girls (mean age 11.9)	Plasma concentrations of DHEA, DHEA-S, and other gonadal hormones	Externalizing: CBCL, Anxiety: total number of anxiety symptoms from the DISC	Externalizing symptoms and DHEA-S were significantly negatively associated in girls. Anxiety symptoms and DHEA were significantly positively associated in boys.
Constantino et al. (1993) PMID: 8282667	18 boys, aged 4–10 years, that were hospitalized for aggressive behavior and had Conduct Disorder, and 18 age- and race-matched controls	Serum concentrations of DHEA and DHEA-S, and other hormones.	Boys in the aggressive group met DSM-III criteria for Conduct Disorder and scored >98th percentile on the aggression subscale of the CBCL	There were no significant group differences in concentrations of any hormones.
Susman et al. (1987) PMID: 3608660	56 boys and 52 girls, aged 9–14 years (all 5 stages of gonadal development)	Serum levels of gonadotropins, gonadal steroids, adrenal androgens (including DHEA and DHEA-S), and testosterone-estradiol binding globulin	Emotional dispositions: self-reported anger, nervousness, sadness, and impulse control. Aggressive attributes: mother-reported acting out, aggressive behavior problems, and rebellious and nasty characteristics	For DHEA/DHEA-S only: Girls: DHEA-S positively associated with self-reported calmness, and negatively associated with parent-reported aggressiveness and nasty behavior. Boys: DHEA positively associated with self-reported sadness and parent-reported rebelliousness, and DHEA-S negatively associated with self-reported impulse control and parent-reported delinquency
Nottelmann et al. (1987) PMID: 3819952	Same sample as Susman et al. (1987).	See Susman et al. (1987).	“Self-image problems”/adjustment from the self-report Offer Self-Image Questionnaire for Adolescents. Mother-report of internalizing and externalizing symptoms on the CBCL.	For DHEA/DHEA-S only (analyses only reported separately by sex): Girls: Negative association between DHEA-S and social self-image problems (controlling for age and pubertal status), and internalizing and externalizing symptoms (not controlling for age and pubertal status). Boys: No significant associations between DHEA/DHEA-S and self-image problems, but a negative association between DHEA-S and hyperactive symptoms (only when not controlling for chronological age and Tanner pubertal status).