Background
Methods
Ethics statement
Subjects
Healthy controls (n = 58) | Patients (n = 55) |
t-test, ANOVA, other t(F)-value
|
P-value
| |
---|---|---|---|---|
Demographics | ||||
Age (years) |
13.8 ± 2.1
|
14.3 ± 1.9
|
1.21
|
0.4
|
Gender (Males/Females) |
40 M/18 F
|
21 M/34 F
|
Fisher Exact
|
0.01
|
Early Adversity |
0
|
11
|
Fisher Exact
|
<0.001
|
Socioeconomic Status |
4.1 ± 0.6
|
4.0 ± 0.7
|
2.62
|
0.11
|
Clinical Characteristics | ||||
SDS Score* |
36.47 ± 6.19
|
56.95 ± 6.42
|
(−235.96)
|
<0.001
|
DSRS-C Score* |
7.51 ± 4.33
|
21.92 ± 6.23
|
(189.03)
|
<0.001
|
Full Scale IQ* |
109.56 ± 12.15
|
94.29 ± 16.49
|
−6.43
|
0.01
|
Verbal IQ* |
105.74 ± 9.92
|
89.24 ± 17.37
|
−9.44
|
0
|
Performance IQ* |
108.74 ± 10.69
|
95.78 ± 15.60
|
7.67
|
0.01
|
Verbal Comprehension Index* |
109.12 ± 13.00
|
92.38 ± 22.08
|
9.05
|
0
|
Perceptual Organization* |
104.41 ± 11.98
|
88.90 ± 21.67
|
4.2
|
0.04
|
Freedom from Distractibility* |
107.35 ± 12.39
|
91.7 ± 22.36
|
3.27
|
0.08
|
Processing Speed Index* |
109.06 ± 10.50
|
89.92 ± 25.61
|
7.99
|
0.01
|
Youth Self Report Score (total) |
53.9 ± 25.5
|
84.5 ± 35.9
|
23.59
|
<0.001
|
Youth Self Report Score (internal) |
8.3 ± 7.2
|
25.1 ± 8.3
|
63.91
|
<0.001
|
Youth Self Report Score (external) |
10.2 ± 6.7
|
14.1 ± 8.6
|
5.46
|
0.02
|
Assessments
Depression scales
Wechsler Intelligence Scale for Children-Third Edition (WISC-III)
Child Behavior Checklist Youth Self-Report (CBCL-YSR) and SES
Early adversity
Genotyping
Genotypes, n (%) | Allele frequencies, n (%) | ||||
---|---|---|---|---|---|
S/S | S/L | L/L | S | L | |
Patients |
33 (60.0)
|
18 (32.7)
|
4 (7.3)
|
84 (76.4)
|
26 (23.6)
|
Age-matched Controls |
32 (62.7)
|
16 (31.4)
|
3 (5.9)
|
80 (78.4)
|
32 (21.6)
|
Adult Controls |
51 (51.0)
|
47 (47.0)
|
2 (2.0)
|
149 (74.5)
|
51 (25.5)
|
Data analysis
Results
Demographics and IQ
Evaluation of binary logistic regression analyses
Genotype (G)
| |||||
B | SE | Wald |
p value
| OR | 95% CI |
0.11
|
0.32
|
0.119
|
0.730
|
1.12
|
0.600-2.073
|
Adversity (E) | |||||
B | SE | Wald |
p value
| OR | 95% CI |
21.48
|
12118.64
|
0.000
|
0.000
|
2129489594
|
0.000-
|
Gender | |||||
B | SE | Wald |
p value
| OR | 95% CI |
−1.06
|
0.4
|
7.11
|
0.01
|
0.35
|
0.158-0.754
|
Age | |||||
B | SE | Wald |
p value
| OR | 95% CI |
0.09
|
0.1
|
0.73
|
0.39
|
1.09
|
0.894-1.332
|
SES | |||||
B | SE | Wald |
p value
| OR | 95% CI |
−0.5
|
0.31
|
2.56
|
0.110
|
0.61
|
0.330-1.119
|
FSIQ | |||||
B | SE | Wald |
p value
| OR | 95% CI |
−0.07
|
0.02
|
10.9
|
0
|
0.93
|
00.892-0.971
|
Gene × Environment(E) | |||||
B | SE | Wald |
p value
| OR | 95% CI |
20.86
|
13894.65
|
0.000
|
0.000
|
1142607181
|
0.000-
|
Evaluation of multivariable logistic regression analyses
Model1
| ||||||
B | SE | Wald | p value | OR | 95% CI | |
G × E interaction |
−1.39
|
25254.67
|
0.000
|
1.000
|
0.25
|
0.000-
|
Genotype (G) |
−1.54
|
0.98
|
2.447
|
0.12
|
0.22
|
0.031-1.475
|
Adversity (E) |
21.04
|
21970.77
|
0.000
|
1
|
1371627685
|
0.000-
|
Gender |
23.7
|
6397.2
|
0.000
|
1
|
0.000
|
0.000-
|
Age |
0.1
|
0.234
|
0.18
|
0.67
|
1.1
|
0.697-1.747
|
SES |
−1.64
|
0.77
|
0.000
|
1
|
1371627685
|
0.000-
|
FSIQ |
−0.79
|
0.39
|
4.057
|
0.04
|
0.92
|
0.855-0.998
|
Fit index of this model: χ2 = 61.216 (p < 0.001), -2log likelihood = 37.706, discriminate accuracy = 96.9% | ||||||
Model2
| ||||||
B | SE | Wald | p value | OR | 95% CI | |
Genotype (G) |
−1.54
|
0.98
|
2.447
|
0.12
|
0.22
|
0.031-1.175
|
Adversity (E) |
20.21
|
10910.59
|
0.000
|
1
|
599809518
|
0.000-
|
Gender |
−23.7
|
6393.91
|
0
|
1
|
0.000
|
0.000-
|
Age |
0.1
|
0.23
|
0.18
|
0.67
|
1.1
|
0.697-1.747
|
SES |
−1.64
|
0.77
|
4.567
|
0.03
|
0.2
|
0.043-0.873
|
FSIQ |
−0.08
|
0.04
|
4.06
|
0.04
|
0.92
|
0.855-0.998
|
Fit index of this model: χ2 = 61.216 (p < 0.001), -2log likelihood = 37.706, discriminate accuracy = 96.9% | ||||||
Model3
| ||||||
B | SE | Wald | p value | OR | 95% CI | |
Gender |
−22.31
|
7045.95
|
0
|
1
|
0
|
0.000
|
FSIQ |
−0.088
|
0.04
|
6.08
|
0.01
|
0.92
|
0.853-0.982
|
Fit index of this model: χ2 = 50.660 (p < 0.001), -2log likelihood = 48.262, discriminate accuracy = 96.9% |
Type III sum of squares |
F value
|
P value
| |
---|---|---|---|
genotype (G) |
47.884
|
.302
|
.740
|
adversity (E) |
7.175
|
.091
|
.764
|
gender |
163.720
|
2.066
|
.154
|
genotype (G) × adversity (E) |
117.151
|
.739
|
.480
|
genotype (G) × gender |
82.514
|
.521
|
.596
|
adversity (G) × gender |
2.451
|
.031
|
.861
|