Table 5.

Autonomic nervous system deregulation in ASD

References	Participants	Materials	Main findings	Strengths and limitations
Anderson et al. [62]	Study 1: ASD group (N = 12, M = 11, F = 1, mean age = 50.25 months, range = 30–69 months), down syndrome (DS) group (N = 9, M = 7, F = 2, mean age = 48.67 months, range = 20–73 months), TD group (N = 11, M = 10, F = 1, mean age = 51.73 months, range = 34–69 months) Study 2: ASD group (N = 18, mean age = 57.78 months, range = 39–73 months), TD group (N = 19, mean age = 52.26 months, range = 33–79 months)	Tonic pupil size, saliva sample collection	ASD showed larger pupil size and lower sAA levels than controls; sAA was strongly correlated with tonic pupil size; typical controls showed a linear increase in sAA during the day	Limitations: small sample size, disproportioned M/F ratio in groups of the first study, not stratification in the second study for males and females Strengths: two different studies, presence of two a control groups (healthy individuals and down syndrome)
Pace et al. [64]	ASD group (N = 19, mean age = 10.7 ± 1.2 years), control group (N = 19, mean age = 9.9 ± 1.6 years)	Questionnaire, actigraphy; nocturnal recordings; HRV analysis	Lower mean HR values were found during sleep with respect to those registered during wakefulness; however, the ASD group showed a lower decrease in HR during deep sleep despite the presence of a higher parasympathetic tone	Limitations: small sample size, not stratification in males and females Strengths: presence of a control group
Harder et al. [65]	ASD children (N = 21, all males, mean age = 7.8 ± 1.8 years) and typically developed children (N = 23, M = 18, F = 5, mean age = 8.0 ± 1.9 years)	Polysomnography, HR and HRV	In both groups, HR decreased during non-REM sleep and increased during REM sleep; HR was significantly higher in stages N2, N3 and REM sleep in the ASD group; ASD children showed less HF modulation during N3 and REM sleep; LF/HF ratio was higher during REM; heart rate decreases with age at the same level in ASD and in TD. LF was influenced by age	Limitations: small sample size, ASD children were composed only by males Strengths: controlled study
Tessier et al. [66]	ASD children (N = 13, range 7–12 years, mean age = 10.2 ± 2.1), ASD adults (N = 16, range = 16–27 years, mean age = 22.0 ± 3.8 years), TD children (N = 13, range = 6–13 years, mean age = 10.5 ± 1.8 years), TD adults (N = 17, range = 16–27 years, mean age = 21.1 ± 4.0 years)	Sleep laboratory measures, ECG recordings	Results show that ASD adults had lower HFnu in the morning than TD adults. During REM sleep, adults had higher LF/HF ratio than children, regardless of their clinical status	Limitations: high number of males, ASD participants were medicine-free; LH/FH ratio significance has been largely questioned Strengths: four different equally subdivided groups (children and adults with or without ASD)
Bharath et al. [8]	ASD children (N = 40, M = 24, F = 16, range = 5.25–12 years, mean age = 10 years), TD controls (N = 40, M = 26, F = 14, range = 7.25–11.75 years, mean age = 9 years)	Autonomic index was assessed by the analysis of short term HRV; urinary levels of VMA estimation was used as a biochemical autonomic index	ASD children exhibit lower cardio-vagal activity as measured by HRV and increased sympathetic activity as assessed by urinary VMA compared to that of TD children	Limitations: small sample size, difference in M/F ratio Strengths: presence of a control group similar to ASD ones (same number of participants)
Sheinkopf et al. [59]	Infants later diagnosed with ASD (N = 12, M = 12, F = 0) and controls non-later ASD (N = 106, M = 58, F = 48) range: 1–72 months	HR and RSA	Both groups showed an expected age-related decrease in HR and increase in RSA, without difference in rate of HR decrease over time; ASD infants demonstrated a smaller linear increase in RSA, indicating slower growth in RSA over time in comparison to controls, thus suggesting that differences in physiological regulation may develop with age in ASD	Limitations: small sample size; participants were drawn from a high-risk cohort designed to investigate the developmental effects of prenatal drug exposure, which could have effects on RSA at one moth of age; disproportion between two groups composition Strengths: controlled study
Thapa et al. [61]	ASD group (N = 55, M = 74.5%, F = 25.5%, mean age = 23.11 ± 5.98 years) control group (N = 55, M = 80%, F = 20%, mean age = 22.00 ± 5.24 years)	HRV	Difference in resting-state HRV between adults diagnosed with ASD compared to the neurotypical control group, with lower parasympathetic activity in ASD	Limitations: ASD group had psychiatric comorbidities, whose effect was difficult to determine due to small sample size; two different devices were used to determine HRV; majority of patients were males Strengths: presence of a control group
Mohd et al. [60]	ASD children (N = 6), TD controls (N = 14)	HRV derived from PPG	HRV response can differentiate between ASD and TD children and could contribute to the detection of ASD to facilitate the children getting the best intervention at the earliest possible time	Strengths: controlled study Limitations: small sample size, not stratification in age and sex
Chong et al. [67]	ASD children (N = 13) divided in: dysregulated sleep group (N = 7, M = 63%, F = 37%, mean age = 7.53 ± 1.35 years) Regulate sleep group (N = 6, M = 80%, F = 20%, mean age = 4.46 ± 1.28 years)	Actigraphy for sleep measure, EDA (which included NSSCR and SCL, SCQ for ASD symptoms core, VABS-II for adaptive behavior	Children in the dysregulated sleep group had fewer NSSCRs and lower SCL in the afternoon	Limitations: small and heterogeneous sample; prevalence of males in both groups; absence of a control group Strengths: subdivision in two groups based on facility/difficulty in sleeping

ASD autism spectrum disorder, sAA salivary alpha amylase, HR heart rate, HRV heart rate variation, REM rapid eye movement, HF high frequency, VMA vanillylmandelic acid, TD typically developing, RSA respiratory sinus arrhythmia, PPG photoplethysmography, EDA electrodermal activity, NSSCR non-specific skin conductance responses, SCL skin conductance levels, SCQ social communication questionnaire, VABS-II vineland adaptive behavior scale second edition