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. 2021 Oct 8;22(19):10873. doi: 10.3390/ijms221910873

Table 2.

Hormones in saliva of autistic individuals.

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, η2 = 0.02
dg x time
F(2.20,226.99) = 4.08, η2 = 0.04
EVE—F(1,103) = 6.88, η2 = 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.