Regional differences in cerebral perfusion associated with the alpha-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder.
BACKGROUND
Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the alpha-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD.


METHODS
We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age- and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxe-wise t statistics using SPM2.


RESULTS
We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons).


CONCLUSIONS
This study was limited by the small sample size, and we did not obtain genetic data from the controls.


CONCLUSIONS
Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.
Kim
Boong-Nyun
BN
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul, Republic of Korea.
Kim
Jae-Won
JW
Kang
Hyejin
H
Cho
Soo-Churl
SC
Shin
Min-Sup
MS
Yoo
Hee-Jeong
HJ
Hong
Soon-Beom
SB
Lee
Dong Soo
DS
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002648:Child; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon
D018341:Receptors, Adrenergic, alpha-2