Study Report
Basic Info
Reference |
Brown, A. B., 201121596533
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Citation |
Brown, A. B., J. Biederman, E. Valera, N. Makris, A. Doyle, S. Whitfield-Gabrieli, E. Mick, T. Spencer, S. Faraone and L. Seidman (2011). "Relationship of DAT1 and adult ADHD to task-positive and task-negative working memory networks." Psychiatry Res 193(1): 7-16.
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Study Design |
case-control |
Study Type |
Candidate-gene association study |
Sample Size |
53 cases and 38 controls |
Predominant Ethnicity |
Caucasian |
Gender |
26 female cases, 22 female controls |
Age Group |
Adults
:
ADHD patients: mean age=33.7, SD=10.5 years of 9R-carriers, mean age=37.6, SD=11.2 years of 10R/10R; Controls: mean age=30.7, SD=9.1 years of 9R-carriers, mean age=31.6, SD=11.2 years of 10R/10R
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Detail Info
Summary |
In order to understand the potential mediating effects of task-positive and task-negative networks between DAT1 and diagnosis, we tested effects of genotype and diagnosis on regions of positive and negative BOLD signal change (as measured with fMRI) in 53 adults with ADHD and 38 control subjects during a working memory task. We also examined the relationship of these responses to ADHD symptoms. Our results yielded four principal findings: 1) association of the DAT1 9R allele with adult ADHD, 2) marginal DAT1 association with task-related suppression in left medial PFC, 3) marginal genotypexdiagnosis interaction in the dorsal anterior cingulate cortex, and 4) correlation of DMN suppression to ADHD symptoms. These findings replicate the association of the 9R allele with adult ADHD. Further, we show that DMN suppression is likely linked to DAT1 and to severity of inattention in ADHD. DMN may therefore be a target of DAT1 effects, and lie on the path between the gene and inattention in ADHD. |
Total Sample |
The resulting sample included 91 adult participants: 53 with ADHD, and 38 controls. |
Sample Collection |
Participants were recruited from Massachusetts General Hospital (MGH) clinics and advertisements posted in the Boston area. |
Diagnosis Description |
To assess for psychiatric diagnoseswe administered the Structured Clinical Interview for DSM-IV. To assess ADHD, we used a module derived from the Schedule of Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version. An ADHD diagnosis was made if the DSM-IV criteria were met in childhood and persisted into adulthood. At the time of the clinical interview, the distribution of ADHD subtypes was: combined, N=17 (32%); inattentive, N=18 (34%); hyperactive/ impulsive, N=1(2%); and remitted, N=17 (32%). |
Technique |
Genomic DNA (5 ng) was amplified in a 7 ml reaction using HotStarTaq DNA Polymerase (0.2 U), the proprietary HotStarTaq Buffer (1_), dNTPs (200 mM), and the marker specific primers (0.2 mM). Amplified products were pooled and combined with size standard (LIZ-250) before being analyzed on an ABI-3730. GeneMapper v3.5 was used to analyze the raw results from the ABI3730, however, a genotype was not considered final until two technologists had independently checked (and corrected) the GeneMapper results and were in agreement. |
Analysis Method |
Demographic and behavioral data were analyzed in PASW Statistics 18.0. 2¡Á2 ANOVAs with group (ADHD vs. controls) and genotype (9R-carriers vs. 10R-homozygotes) as fixed factors were run on demographic, clinical, and N-back performance data. |
Result Description |
Our results yielded four principal findings: 1) association of the DAT1 9R allele with adult ADHD, 2) marginal DAT1 association with task-related suppression in left medial PFC, 3) marginal genotypexdiagnosis interaction in the dorsal anterior cingulate cortex, and 4) correlation of DMN suppression to ADHD symptoms. These findings replicate the association of the 9R allele with adult ADHD. Further, we show that DMN suppression is likely linked to DAT1 and to severity of inattention in ADHD. DMN may therefore be a target of DAT1 effects, and lie on the path between the gene and inattention in ADHD. |
Other variant reported by this study (count: 1)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
SLC6A3 3'-UTR VNTR |
9R |
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P-value=0.004, X2=8.34
P-value=0.004, X2=8.34
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There was a statistically significant difference, indicating that the 9R allele was more frequent in the ADHD sample. |
Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A3 |
These findings replicate the association of the 9R allele wi......
These findings replicate the association of the 9R allele with adult ADHD.
More...
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Significant
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