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Increased Dopamine Transporter Availability Associated with the 9-Repeat Allele of the SLC6A3 Gene

Christopher H. van Dyck, MD1,2,3, Robert T. Malison, MD1, Leslie K. Jacobsen, MD1,3, John P. Seibyl, MD1,3,4, Julie K. Staley, PhD1,3, Marc Laruelle, MD1,3, Ronald M. Baldwin, PhD1,3, Robert B. Innis, MD, PhD1,3 and Joel Gelernter, MD1,3

1 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
2 Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut
3 VA Connecticut Healthcare System, West Haven, Connecticut
4 Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut



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  		FIGURE 1. Transaxial 123I-ß-CIT SPECT image at level of striatum. Scan demonstrates ROIs positioned over right and left caudate, right and left putamen, and occipital cortex. Representative attenuation ellipse is also displayed.

 


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  		FIGURE 2. Striatal DAT availability (V3'') vs. age (in years) as measured by 123I-ß-CIT SPECT in 94 healthy European Americans grouped according to SLC6A3 VNTR genotype. SLC6A3*9R carriers (n = 41) had significantly higher striatal DAT availability (V3'') than did SLC6A3*10R homozygotes (n = 53), controlling for age (F1,93 = 6.25, P = 0.014, ANCOVA). Both genotypic subgroups showed similar aging effects: For *9R carriers, V3'' declined by 44% over age range 18–88 y, or approximately 6.3% per decade. For *10R homozygotes, V3'' declined by 43% over age range 18–88 y, or approximately 6.2% per decade.

 


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  		FIGURE 3. DAT availability (V3'') in caudate (A) and putamen (B) vs. age (in years) as measured by 123I-ß-CIT SPECT in 94 healthy European Americans grouped according to SLC6A3 VNTR genotype. SLC6A3*9R carriers (n = 41) had significantly higher DAT availability (V3'') in both caudate (F1,93 = 4.88, P = 0.030, ANCOVA) and putamen (F1,93 = 6.92, P = 0.010, ANCOVA), controlling for age.

 




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