Table 4 Cortisol level and hyperarousal in ASD

Priya Lakshimi et al. [49]

ASD children (N = 45 divided into three groups: low, medium and high functioning. Each group included 15 children. M/F = 36/9, range 4–12 years)

Typically developed children (N = 45, M/F = 36/9, range = 4–12 years)

CARS classification as preliminary screening and urinary level of free cortisol, corticosteroids, VMA, and 5-hydroxyindole acetic determination

Corticosteroids excretion levels were higher in all the groups of children with ASD than in the control group. An alteration in the pattern of cortisol excretion was observed in children with LFA. The level of 5-hydroxyindole acetic acid was higher in children with LFA and MFA than in the control group

Limitations: not determined the blood and saliva levels of corticosteroids, free cortisol, VMA, 5-hydroxyindole acetic acid, and prostaglandin E

Strengths: group of ASF and controls very identical in number composition, M/F ratio and range age

Gabriels et al. [51]

Pre-pubescent ASD males (N = 21, 11 of them with high-RB, and 10 with low RB)

Mean age of high-RB group: 7.8 ± 1.7 years

Mean age of low-RB: 8.1 ± 1.4 years

Range: 3–9 years

Measure of screening: tanner criteria, caregiver-report RBS-R scale, CCIF-RV, SCQ, ADOS, Leiter-R, VABS, BEDS

Other measure: salivary cortisol level

Participants with more severe repetitive behaviors had lower diurnal salivary cortisol than others

Limitations: patients were only males and the sample size was low

Strengths: patients were carefully selected through different scales

Tomarken et al. [50]

ASD children (N = 36, M = 30, F = 6, Mean age 10.20 ± 1.96)

Typically developed controls (N = 27, M = 23, F = 4, mean age = 9.71 ± 1.54)

Total range: 7–16 years

Salivary cortisol collection

A decline in evening levels of cortisol was detected, whereas no difference was reported in the morning levels. 25% of ASD children had an attenuated linear decline in cortisol level, while the trajectory of the other ones was indistinguishable from that of TD children

Limitations: disproportioned M/F ratio in both groups

Strengths: controlled study

Sharpley et al. [53]

ASD girls (N = 39)

Mean age = 10.1 ± 2.7 years

Range = 6–17 years

CASI, WASI-II, ADOS-2, DF of cortisol and CAR

Over half of the participants showed inverse CAR and over 14% had inverted DF cortisol concentrations; three potential sets of predictor factors (physiological, ASD-related, and mood) revealed that only self-reported Major Depressive Disorder was significantly associated with CAR status, and that the girls' concern about dying or suicide was the most powerful contributor to the variance in CAR status

Limitations: sample size; statistical power; cultural and geographical isolation; use of a snap-shot design rather than a prospective design; collection of salivary cortisol on a single day; one third of the cohort reported thoughts of “dying or killing oneself; it is not a direct comparison study

Muscatello et al. [48]

ASD youths (N = 64, M = 57, F = 7, mean age 12.02 years) and typically developed youths (N = 49, M = 42, F = 7, mean age = 11.17 years)

Total range = 7–17 years

Diagnostic and assessment measures: ADOS, WASI, SCQ, SRS-2, PDS, CBCL, SSS, SES, Salivary cortisol sampling

ASD child, pubertal and adolescents had significantly higher evening cortisol than controls. Adolescent had higher cortisol levels than children

Limitations: predominantly male sample and differences in IQ between groups; the current sample consisted only of those with high-functioning ASD; numeric disproportion between males and females included

Strengths: large ASD sample and a comprehensive age range of children and adolescents

Baker et al. [7]

ASD adults (N = 29, M = 51.7%, F = 48.3%, 13 of them were medicated for comorbid anxiety or ASD-Med with mean age = 33.93 ± 6.53 years 16 were drug-free or ASD-only with mean age = 33.55 ± 6.50) and controls (N = 29, mean age = 30.99 ± 5.25 years)

Participants completed a questionnaire battery, 14-day sleep/wake diary and 14-day actigraphy assessment; On one day during the data collection period, participants collected five saliva samples, hourly, prior to sleep and two morning samples, immediately upon waking and 30 min thereafter for the analysis of cortisol

ASD participants reported greater reduction in evening cortisol concentrations when compared with controls; In the ASD group, poor sleep efficiency and increased wake duration was significantly correlated with cortisol levels measured 1 h before habitual sleep onset time; increased sleep onset latency and poorer sleep efficiency was associated with higher subjective arousal in the ASD group

Limitations: cortisol was not retained in the model; comorbid diagnoses of anxiety and depression in the ASD-Med group were not confirmed with clinical interviews; small sample sizes

Strengths: controlled study with proportioned ASD and controls group; subdivision into ASD group in ASD-Only and ASD-Med

Anesiadou et al. [54]

Four groups: ASD children (N = 56, M = 49, F = 7 mean age = 8.40 ± 1.60 years) ADHD children (N = 34, M = 22, F = 12, mean age = 8.79 ± 1.43 years), SLD children (N = 43, M = 25, F = 18, mean age = 9.55 ± 1.64 years), TD group (N = 24, M = 16, F = 8, mean age = 9.74 ± 1.98 years)

APT, moral cognition task, sAA

ASD children showed lower diurnal sAA secretion, adjusted for age, compared to typically developed ones; sAA evening levels resulted significantly higher in ADHD group compared to controls; the academic performance task increased sAA levels in ASD children, while the moral cognition task did not activate the sympathetic nervous system in any group

Limitations: cross-sectional design does not allow us to make inferences; small sample size of population; sample procedure to a single day; lack of multiple time point sampling; disproportion in M/F ratio between groups

Strengths: four different groups