Table 1.

Characteristics and findings from existing empirical studies of SAM-HPA co-activation in children and adolescents.

Study	Study Sample	Saliva Sampling	Biomarker Indices	Covariates	Findings: Associated with Psychopathology
					Symmetrical	Asymmetrical
Allwood, Handwerger, Kivlighan, Granger, and Stroud (2011)	56 children (ages 7-16) inclusion criteria: fluent in English exclusion criteria: use of oral contraceptives, thyroid medications, steroids, psychotropic medications, tobacco, drugs, and alcohol; history of psychological or behavioral problems; current physical illnesses.	acute stress exposure: 7-9 saliva samples taken over baseline, stress, and recovery periods; stress tasks included 3 tasks, either TSST with mirror tracing or a peer rejection task; 6 time-matched samples were used to account for time-to-peak lag of cortisol and AA	use baseline measures and peak (maximum value of cortisol or AA post-stressor onset)	sex, age, and stressor type		Low AA reactivity in conjunction with high cortisol reactivity predicted greater parent reports of child total problems (attention problems and social problems) and greater internalizing problems.
Bae, Stadelmann, Klein, Jaeger, Heimisch, Keiss et al., 2015	169 children (ages 8-14); selected on the basis of presence of internalizing (n=55) or externalizing (n=33) disorders; healthy control group (n=81) also included inclusion criteria: fluent in German; IQ > 80; no concurrent endocrine diseases or use of glucocorticoid medications	circadian activity: saliva collected at wakening, 30 min after waking, and 30 min before bedtime over 3 days acute stress exposure: 8 saliva samples (3 pre-, 5 post) across TSST-C	Calculated reactivity (difference between highest post-TSST-C and lowest pre-TSST-C) and recovery (difference between highest post- TSST-C and lowest post- TSST-C)	gender, age, height, BMI, Tanner pubertal stages	Low AA baseline and low cortisol reactivity was associated with more externalizing problems.	High AA recovery and low cortisol reactivity associated with more internalizing problems.
Chen, Raine, Rudo-Hutt, Glenn, Soyfer, & Granger, 2014	425 children (ages 11-12). Exclusion criteria: diagnoses of psychotic disorder, mental retardation, pervasive developmental disorder, current psychiatric treatment or treatment; current use of medication known to interfere with measurement of salivary analytes.	circadian activity: 3 saliva samples collected across one morning in the laboratory, starting at approximately 9:19am (SD=20 minutes), then second 15 minutes later, and third 30 minutes later.	Levels of biomarkers modeled as latent variables with three corresponding sample analytes as indicators	pubertal stage, body mass index, household income, and ethnicity	For boys with high AA, as cortisol increased, the effect of harsh discipline on externalizing and internalizing problems decreased. No interaction for girls.	Among boys with low AA, as cortisol increased the effect of harsh discipline on externalizing and internalizing problems increased. No significant interaction for girls.
Chen, Raine, Soyfer, & Granger, 2015	Same sample used in Chen et al, 2014. 429 children (ages 11-12). See Chen et al, 2014, for exclusion criteria.	circadian activity: saliva collected four times across the day (3 in the morning at 15-minute intervals, and 4th sample in afternoon before series of lab tasks)	“Trait-like” indices of biomarkers modeled as latent variables with four corresponding sample analytes as indicators.	age, gender, ethnicity, saliva collected time	Children with low “trait-like” AA and cortisol together were more likely to have higher scores of externalizing problems.	Children with low sAA and high cortisol were significantly more likely to have lower levels of internalizing problems.
Chen, Raine, Glenn, & Granger, 2016	Same sample used in Chen et al, 2014, with the addition of follow up assessments at 3-, 6-, and 12-month follow-up. 394 children (ages 11-12 at initial assessment). See Chen et al, 2014 for initial exclusion criteria. After initial assessment, children with elevated externalizing behavior were randomized into treatment or control group. Intervention administered between initial assessment and 3-month follow up.	circadian activity at initial assessment: see Chen et al 2014 for procedure	Levels of biomarkers modeled as latent variables with three corresponding sample analytes as indicators	age, sex, ethnicity, Tanner puberty stage, treatment assignment		Among children who had high latent cortisol at initial assessment, as AA decreased, the odds of having comorbid externalizing and internalizing problems across time points increased. For children with low latent cortisol, the probability of having stable comorbidity and high levels of symptoms was high regardless of latent AA level.
de Vries-Bouw, Jansen, Vermeiren, Doreleijers, van de Ven, & Popma, 2012	64 male adolescents (Mage = 18.4 years, SD=.9); recruited from delinquency diversion program (DP; n=48) or from community as matched controls (n=16). Of those boys in the delinquent group, 15 boys (DP+) had a DBD by self- or parent-report and 33 boys (DP−) did not.	acute stress response: 7 saliva samples (2 pre- and 4 post-stressor task, a public speaking task in front of a one-way screen with video recording)	basal: biomarker levels in saliva sample 2 (immediately before start of stress task) was used; reactivity: AUCi across samples 2-6	nicotine use	Interaction between AA and cortisol not significantly associated with disruptive behavior.
El-Sheikh, Erath, Buckhalt, Granger, and Mize, (2008)	64 children (Mage = 8.72, SD=0.47); exclusion criteria: parent report of child chronic/acute physical illness, clinically significant sleep disorders mental retardation, learning disabilities, ADHD	circadian activity: 2 saliva samples collected (1) 20 min after arrival, (2) 2 hours later, post-stressor (listen to interadult argument, complete star-tracing tasks; known to elicit SCL reactivity, but wouldn’t expect it to elicit cortisol);	samples were averaged to represent basal levels	gender, ethnicity, age, SES and time of saliva sampling	Concordantly high basal AA and cortisol predicted higher parent reports of child externalizing and internalizing problems.	High basal AA and low cortisol associated with lower levels of parent-reported externalizing and internalizing behaviors.
Gordis, Granger, Susman, & Trickett, 2006	67 youth (ages 10-14.5), with maltreated group (n=35) and non-maltreated (n=32). Exclusion criteria: use of synthetic corticosteroids or beta-adrenergic agonists or hormone contraceptives.	Acute stress response: 6 saliva samples (2 pre- and 4 post-TSST)	Acute response: Calculated AUC with respect to ground across 6 time points	maltreatment status, child sex, age, time of day		For children with low AA response, higher cortisol response predicted lower reports of child’s aggression. For children with high AA, there was no effect of cortisol on parents’ report of aggression.
Koss, George, Cummings, Davies, El-Sheikh, & Cicchetti 2014	176 families (mothers, fathers, and 2nd grade child; Mage = 7.99 years, SD=.53) participated in T1 (2nd grade) and T2 (early adolescence, mean grade=7th; Mage =12.55 years, SD=.56). Inclusion criteria: all 3 family members living together for a minimum of 3 years, families had a child in kindergarten at start of study, all family members proficient in English.	Acute Stress Response: 2 saliva samples collected pre- and 25-minutes post-stressor task, in which children viewed martial conflict vignettes.	Acute response: post-stressor biomarker levels (controlling for pre-stressor levels)	Assessment time, pre-task cortisol and AA levels, tape stimuli, child gender, child age, family income	Children with low AA-low cortisol in 2nd grade had more concomitant internalizing problems when in low conflict homes. This was not true for children in high conflict homes with the low AA-low cortisol pattern. 7th graders with high AA-high cortisol had more externalizing problems, but only in low conflict homes.	Children from high conflict homes with high AA-low cortisol in 2nd grade had high levels of concurrent and prospective internalizing problems. Adolescents in 7th grade with high AA-low cortisol in 2nd grade had more externalizing problems when from high conflict homes.
Kreher, Powers, & Granger, 2012	109 female undergraduate students (Mage = 19). Inclusion criteria: native speaker of English, normal or corrected-to-normal vision. Participants received course extra credit for study participation.	Baseline: provided one late afternoon/early evening saliva sample upon arrival to the lab on three lab sessions. Appointments were scheduled to begin 8-10 hours after waking	Biomarker values were averaged across the three days.	medication and marijuana use	Among women with high AA, those with higher cortisol exhibited greater priming to negative words.	Among women with low AA, there was no significant relationship between cortisol and negative valence priming.
Platje, Jansen, Vermieren, Doreleijers, van Lier, Koot et al., 2017	197 adolescents (Mage = 17.31 years, SD=.44). Recruited for longitudinal Dutch population based cohort study, with oversampling of children with borderline clinical score on externalizing behaviors by teacher report at age 11.	Cortisol awakening response: Collected 3 saliva samples, immediately after awakening, then 30 and 60 minutes later. Acute stress response: Provided 8 saliva samples, 2 pre-, 1 during, and 5 post-completion of the Leiden PST.	CAR: Calculated AUC with respect to ground across the three morning samples. Acute response: Calculated AUC with respect to increase across time points 2-5 (just before start of task until 15 minutes after stressor).	gender, nicotine use	The interaction approached significance (p=.076), but suggested that for youth with high AA, high cortisol reactivity was associated with higher externalizing behavior.	The interaction approached significance (p=.076), but suggested that for youth with low AA, high cortisol reactivity was associated with lower externalizing behavior.