White matter alterations related to attention-deficit hyperactivity disorder and COMT val¹⁵⁸met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus)

Figures & data

Table 1 Sociodemographic characteristics and estimated WISC-R scores of the diagnostic groups and COMT genotypes

Sociodemographic characteristics and WISC-R scores of ADHD and healthy control groups
	ADHD (n=71)	Healthy controls (n=24)	Total (n=95)	t/χ^2 values	P-values
Age, mean ± SD	10.88±1.36	10.80±2.02	10.82±1.87	t=0.196	*P=0.845
Sex, male, n (%)	59 (83.1%)	18 (75%)	77 (81.1%)	χ^2=0.766	**P=0.381
Estimated IQ, mean ± SD	109.42±18.60	111.45±17.84	109.93±18.34	t=0.468	*P=0.641
Sociodemographic characteristics and WISC-R scores of COMT genotype groups
	GG (n=36)	GA (n=41)	AA (n=18)	F/χ^2 values	P-values
Age, mean ± SD	10.64±1.55	11.22±2.11	10.28±1.77	F=1.889	***P=0.157
Sex, male, n (%)	32 (88.8%)	31 (75.6%)	14 (77.7%)	χ^2=2.356	**P=0.308
Estimated IQ, mean ± SD	112.61±18.39	107.80±17.92	109.44±19.54	F=0.661	***P=0.519

Notes:

* Independent sample’s t-test;

** chi-square test;

*** one-way ANOVA. AA, met/met; GA, val/met; GG, val/val.

Abbreviations: ADHD, attention-deficit hyperactivity disorder; ANOVA, analysis of variance; WISC-R, Wechsler Intelligence Scale for Children-Revised.

Table 2 The effect of the COMT genotypes on the white matter tracts

COMT genotypes (total n=95)
	L/R	Val/val (GG), mean ± SD (n=36)	Met carrier (GA + AA), mean ± SD (n=59)	F	P-value*	σ^2
FA
EC	R	0.353±0.015	0.362±0.017	3.420	0.068	0.043
UNC	L	0.374±0.024	0.393±0.036	5.816	0.018	0.063
MD
PTR (include OR)	R	0.861±0.032	0.848±0.033	4.027	0.048	0.044
PTR (include OR)	L	0.859±0.031	0.844±0.035	4.738	0.032	0.052
SLF	R	0.773±0.023	0.761±0.024	3.604	0.061	0.040
AD
UNC	L	1.221±0.033	1.242±0.045	5.603	0.020	0.061
RD
PCR	L	0.641±0.033	0.618±0.032	7.001	0.010	0.074
PTR (include OR)	R	0.603±0.033	0.587±0.036	4.799	0.031	0.052
PTR (include OR)	L	0.612±0.026	0.592±0.032	6.521	0.012	0.073
SLF	R	0.605±0.024	0.592±0.023	3.490	0.065	0.039

Notes:

* MANCOVA, Bonferroni adjustment was used, bold values indicate P<0.025 was accepted as significant. The effect of the diagnosis, age, sex, and estimated IQ was controlled. AA, met/met; GA, val/met; GG, val/val.

Abbreviations: AD, axial diffusivity; EC, external capsule; FA, fractional anisotropy; L, left; MANCOVA, multivariate analysis of covariance; MD, mean diffusivity; OR, optic radiation; PCR, posterior corona radiata; PTR, posterior thalamic radiation; R, right; RD, radial diffusivity; SLF, superior longitudinal fasciculus; UNC, uncinate fasciculus.

Table 3 The effect of ADHD on the white matter tracts

ADHD/control (total n=95)
	L/R	Control, mean ± SD (n=24)	ADHD, mean ± SD (n=71)	F	P-value*	σ^2
FA
FX		0.411±0.031	0.391±0.041	3.551	0.063	0.039
Cerebellar peduncle	R	0.565±0.025	0.571±0.020	4.639	0.034	0.050
CGC	R	0.345±0.026	0.341±0.024	4.813	0.031	0.052
CGC	L	0.365±0.024	0.358±0.027	5.936	0.017	0.063
RLIC	R	0.519±0.015	0.508±0.022	7.324	0.007	0.080
AD
Sagittal striatum	R	1.362±0.044	1.337±0.046	3.558	0.063	0.039
CGC	R	1.123±0.039	1.101±0.047	3.768	0.055	0.041
FX/ST	R	1.494±0.069	1.456±0.066	4.764	0.032	0.052

Notes:

* MANOVA, Bonferroni adjustment was used, bold values indicate P<0.025 was accepted as significant. The effect of the COMT genotypes, age, sex, and estimated IQ was controlled.

Abbreviations: AD, axial diffusivity; ADHD, attention-deficit hyperactivity disorder; CGC, cingulum (cingulate gyrus); FA, fractional anisotropy; FX, fornix (column and body); MANCOVA, multivariate analysis of covariance; L, left; R, right; RLIC, retrolenticular part of the internal capsule; ST, stria terminalis; FX/ST: fornix (cres) stria terminalis.

Figure 1 Axial R-CGC bundle 3D, coronal, sagittal, and axial images.

Abbreviations: A, anterior; CGC, cingulum (cingulate gyrus); 3D, three dimensional; F, foot; H, head; L, left; R, right; P, posterior.

Figure 2 Interaction effects- R-CGC FA values.

Notes: Mean R-CGC FA value difference was 0.018 (95% CI, 0.008–0.028) points, which was higher for met carriers than for val homozygotes in the ADHD group. For patients with ADHD and controls with val/val genotype, mean R-CGC FA value difference was 0.024 (95% CI, 0.011–0.038) points, which was higher for controls than for patients with ADHD. ^*P=0.001.
Abbreviations: ADHD, attention-deficit hyperactive disorder; CGC, cingulum (cingulate gyrus); FA, fractional anisotropy; met, methionine; R, right; val, valine.

Figure 3 Interaction effects- R-CGC RD values.

Notes: ADHD-diagnosed met-carrier children had statistically significantly lower mean R-CGC RD value than val homozygotes 0.018 points (95% CI, 0.004–0.033). For patients with val homozygote ADHD and controls, mean R-CGC RD value difference was 0.023 (95% CI, 0.003–0.043) points, which was lower for controls than for patients with ADHD. *P<0.025.
Abbreviations: ADHD, attention-deficit hyperactive disorder; CGC, cingulum (cingulate gyrus); met, methionine; R, right; RD, radial diffusivity; val, valine.