Table 2.
Children No. ASD No. CTRL Geographic Region |
Dg. Tool/ ASD Module |
Age (Years) ASD CTRL |
Timing | Saliva | Duration of Sal/Volume | Centrif | Marker | Concentration ASD, CTRL |
Method | Results ↓↑ |
Ref |
---|---|---|---|---|---|---|---|---|---|---|---|
High functioning ASD 37 M 2 F NA |
ADIR/ NA |
8.64 ± 1.50 | NA | UWMS Salivette Sorbette |
NA 45 s |
NA | µg/dL Cortisol |
RM ANOVA F(2,37) = 0.53 Mean (SD) 0.089 (0.045) 0.084 (0.036) 0.084 (0.035) |
ELISA | p = 0.592 | [29] |
ASD M 23 CTRL M 21 ASD F 22 CTRL F 16 22 markers were analyzed, also in saliva of females Poland |
DSM-IV CARS/ NA |
3.7 ± 0.1 3.5 ± 0.1 3.9 ± 0.2 3.4 ± 0.1 8.2 ± 0.2 8.4 ± 0.2 7.7 ± 0.2 8.4 ± 1.4 |
8–10 a.m. | Salivette | 0.15–5 mL | Frozen 3000- 4000 g, 10 min |
nmol/L DHEA-C Androsterone-C Pregnenolone Allopregnanolone DHEA DHEA-C Androstenediol Etiocholanolone Epiandrosterone |
Mean (±SEM), ASD, CTRL boys 69.66 (30.05); 7.702 (1.440) 6.972 (1.767); 3.0.57 (0.770) ASD, CTRL males 4.454 (0.682); 1.295 (0.133) 0.177 (0.029); 0.030 (0.008) 5.522 (1.934); 0.880 (0.106) 560.05 (278.11); 39.06 (23.82) 1.746 (0.206); 0.637 (0.091) 0.0702 (0.014); 0.015 (0.003) 0.402 (0.223); 0.075 (0.011) |
GC-MS RIA |
↑ ASD (0 < 0.05) ↑ ASD (p = 0.010) ↑ ASD (p < 0.05) ↑ ASD (p < 0.05) ↑ ASD (p < 0.01) ↑ ASD (p < 0.01) ↑ ASD (p < 0.01) ↑ ASD (p < 0.01) ↑ ASD (p < 0.01) |
[93] |
ASD 20 M ASDanx 32 M CTRL 23 M United Kingdom |
ADOS-G ADI-R SCQ/ NA |
13.9 (1.9) 12.9 (2.0) 12.8 (2.0) |
1:20 p.m. 1:40 p.m. |
Salivette | NA | NA | Unit NA Cortisol |
Log-transformed, F(2,72) = 0.06 F(2,72) = 0.11 Mean (SD) 13:20 p.m., 13:40 p.m. 1.77 (0.53); 1.82 (0.50); 1.80 (0.46) 1.56 (0.41); 1.54 (0.40); 1.59 (0.34) |
Immulite | - | [94] |
ASD 49 M CTRL 28 M The Netherlands |
DSM-V DISC-IV/ NA |
15.0 ± 1.8 15.9 ± 2.1 |
6:45 a.m.–12:30 p.m. | UWMS | NA/6 mL | Non-C | Oxytocin Testosterone Cortisol |
Calculated as Z scores (SD) −0.22 (0.89); 0.49 (0.97) −0.26 (0.99); −0.04 (0.74) −0.19 (1.02); 0.02 (0.75) |
RIA | Oxytocin ↓ ASD (p < 0.01) |
[95] |
ASD 30 M, 6 F CTRL 23 M, 4 F NA |
ADOS DSM-IV/ NA |
10.2 ± 1.96 9.71 ± 1.54 |
M1—waking M2—30 min after A—approx. 3 p.m. E-30 min bedtime |
UWMS | NA | Frozen 2558 g 15 min |
ng/mL Cortisol |
Diagnosis-F(1,128) = 4.78 M1-F(1,103) < 1 M2-F(1,123) < 1 A-F(1,110) < 1 E-F(1,122) = 7.86 Mean (SD) M1—2.86 (1.20); 2.54 (1.11) M2—3.58 (1.60); 3.23 (1.46) A—1.40 (1.73); 0.83 (0.35) E—0.47 (0.59); 0.18 (0.14) |
Coat-A-count RIA |
p = 0.031 p = 0.50 p = 0.76 p = 0.40 ASD p = 0.006 |
[96] |
ASD 57 M, 7 F CTRL 42 M, 7 F NA |
ADOS DSM-V/ NA |
12.02 11.17 |
M1—waking M2—30 min after AFT—1–4 p.m. EVE-30 min bedtime |
straw | 1 mL | Frozen 3640 rpm 15 min |
ng/mL Cortisol-C |
dg x C—F(1,103) = 1.73, 2 = 0.02 dg x time F(2.20,226.99) = 4.08, 2 = 0.04 EVE—F(1,103) = 6.88, 2 = 0.06 Log-transformed Mean (SD) M1—0.33 (0.25); 0.34 (0.26) M2—0.44 (0.31); 0.48 (0.19) AFT—−0.05 (0.32); −0.10 (0.28) EVE—−0.60 (0.40); −0.81 (0.41) |
Coat-A-count RIA |
p = 0.19 p = 0.02 ↑ ASD (p = 0.01) p = 0.82 p = 0.45 p = 0.42 ↓ ASD p = 0.01 |
[97] |
LF ASD 36 M,19 F CTRL 22 M, 12 F France |
DSM-5 ICD-10 CFTMEA ADOS-G ADI-R/ module 1 |
11.3 ± 4.1 11.7 ± 4.9 |
8 a.m. 11 a.m. 4 p.m. 0 a.m. 8 a.m. next day |
swab | >1 min | NA | µg/dL Cortisol |
Mean (SEM) 0.803 (±0.134); 0.620 (±0.070) 0.529 (±0.94); 0.429 (±0.089) 0.365 (±0.048); 0.201 (±0.018) 0.305 (±0.077); 0.104 (±0.002) 1.209 (±0.167); 0.620 (±0.071) RM measures of variance Group–F(1,31) = 20.74 Time–F(4,124) = 54.07 Group by time –F(4,124) = 1.59 |
ELISA |
p = 0.2318 p = 0.2154 ↑ ASD p = 0.0017 ↑ ASD p = 0.0001 ↑ ASD p = 0.0016 p < 0.001 p < 0.001 p = 0.187 |
[98] |
ASD 12 M CTRL 10 M California |
ADOS DSM-IV/ NA |
8.5 9.2 |
1–3 p.m. (1) Eve—30 min of bedtime M-30 min post-waking 1–3 p.m. (2) Eve (2) M (3) |
Chewing gum, straw |
30 s | Frozen 6000 rpm 10 min |
nmol/L Cortisol |
Log-transformed NA |
RIA | Overall cortisol level—p = 0.45 Daily variations p > 0.08 (for interactions between ASD and both time of day contrasts) |
[99] |
ASD 16 F CTRL 29 F NA |
DSM-V ICD-10/ NA |
18–50 29.9 ± 8.4 28.7 ± 9.0 |
NA | UWMS | NA | NA | pg/mL Estradiol Testosterone Oxytocin |
Mean (SD) 1.0 (±0.3); 1.2 (±0.5) 70.3 (±24.9); 69.4 (±21.4) 3.1 (±0.5); 2.8 (±0.16) |
ELISA RIA |
p = 0.19 p = 0.91 p = 0.064 |
[102] |
ASD 17 M CTRL 24 M Japan |
DSM-V DISCO/ NA |
27.4 ± 7.2 29.0 ± 9.8 |
NA | Salivette | NA | NA | pg/mL Oxytocin |
36.2 (13.2); 43.6 (17.0) | ELISA | p = 0.154 | [103] |
ASD 11 M, 9 F CTRL 15 M,13 F NA |
ADOS DSM-IV-TR CARS/ NA |
3–10 |
Before blood draw 20 min after 40 min after |
Salivette Sorbette |
NA | NA | µg/dL; log-transformed Cortisol |
Mean (SEM), ASD; CTRL 0.242 (0.061); 0.175 (0.024) 0.426 (0.107); 0.132 (0.018) 0.329 (0.111); 0.011 (0.018) |
EIA |
p = 0.242 p = 0.014 ↑ ASD p = 0.057 |
[104] |
ASD M 22, F 4 CTRL M 23, F 3 NA |
ADOS-G ADI-R DSM-IV/ NA |
Age in months 45.1 ± 8.9 39.4 ± 10.5 |
Waking within 30 min Midday 2 p.m. Bedtime within 30 min Waking 2 Midday 2 Bedtime 2 |
Kool-Aid drink swab |
0.5–1.0 mL | nmol/L Cortisol |
Coefficient 0.17 (CI, −0.08–0.49) | ELISA Kinetic reaction assay |
p > 0.23 | [109] | |
ASD 21 M, 1 F CTRL 19 M, 3 F California |
ADOS ADI DSM-IV/ NA |
8.81 ± 1.90 9.35 ± 1.75 |
M1—waking A1—afternoon (1–4 p.m.) E1—30min bedtime Collection 6 days during 2 weeks |
chewing gum | NA | Refrigerated until the end of collection Frozen 6000 rpm 10 min |
nmol/L Cortisol M1 A1 E1 M2 A2 E2 M3 A3 E3 M4 A4 E4 M5 A5 E5 M6 A6 E6 |
Mean (SD), ASD; CTRL 15.60 (16.90); 11.40 (6.87) 3.90 (2.92); 3.14 (1.34) 2.31 (3.39); 1.46 (0.72) 10.30 (3.39); 9.83 (4.63) 3.25 (2.17); 3.03 (1.57) 2.53 (3.18); 1.26 (0.21) 11.70 (7.07); 12.10 (5.97) 3.60 (3.20); 3.22 (1.64) 4.94 (12.0); 1.40 (0.30) 11.20 (5.02); 11.30 (5.81) 4.84 (4.94); 2.97 (1.30) 2.50 (2.86); 1.31 (0.46) 8.88 (4.14); 11.60 (6.50) 4.76 (3.68); 3.40 (1.54) 2.05 (1.63); 1.53 (0.57) 8.15 (6.12); 10.70 (4.29) 4.60 (7.72); 3.17 1.77) 3.07 (4.56); 1.53 (0.57) |
RIA | E concentration over 6 days p = 0.021 E2-E5 ↑ ASD p < 0.04 Multiple regression Time p > 0.05 Sleep p > 0.05 Age p > 0.05 |
[110] |
ASD 50 CTRL 50 NA |
NA/ NA |
6–12 | 2× 8–8:30 a.m. 2× 4–4:15 p.m. |
UWMS | 2 min drooling intervals/2mL | Non-C | Cortisol (NA) 1st day morning 1st day evening 2nd day morning 2nd day evening |
Mean (SD) 57.12 (14.108); 96.16 (15.694) 101.4 (17.647); 66.39 (11.735) 57.96 (13.883); 96.73 (16.569) 102 (17.827); 66.55 (12.099) |
ECL | ↓ ASD (<0.001) ↑ ASD (<0.001) ↓ ASD (<0.001) ↑ ASD (<0.001) |
[111] |
ADOS-G—Autism Diagnostic Observation Schedule-Generic; ADIR—Autism Diagnostic Interview-Revised; ASD—autism spectrum disorder; ASDanx—ASD with an anxiety disorder; AT a/b—5-androstene-3b;7a/b;17b-triol; CTRL—control; CARS—Childhood Autism Rating Scale; Dg—diagnosis; Dg tool—diagnostic tool; DISC-N—Diagnostic Interview Schedule for Children; DISCO—Diagnostic Interview for Social and Communication Disorders; DHEA—dehydroepiandrosterone; DHEA-C—dehydroepiandrosterone conjugate; DSM—diagnostics and statistical manual; ECL-electrochemiluminescence; GxT—group by time interaction; IQR—inter-quartile range 25–75%; LC-MS/MS—liquid chromatography-mass spectrometry; LF ASD—low functioning autism; NA—not applicable or mentioned in the text; Non-C—non-centrifuged; RM ANOVA—repeated measures ANOVA; RIA—radioimmunoassay; SCQ—Social Communication Questionnaire; SD—standard deviation; SEM—standard error mean; UWMS—unstimulated whole mouth saliva; ↑/↓—higher/lower concentration in autism; NA—not applicable or mentioned in the text.