Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain

被引:209
作者
Parsey, RV
Hastings, RS
Oquendo, MA
Hu, XZ
Goldman, D
Huang, YY
Simpson, N
Arcement, J
Huang, YY
Ogden, RT
Van Heertum, RL
Arango, V
Mann, JJ
机构
[1] New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA
[2] New York State Psychiat Inst & Hosp, Dept Analyt Psychopharmacol, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA
[4] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA
[5] Columbia Univ, Sch Publ Hlth, Dept Biostat, New York, NY USA
[6] NIAAA, Neurogenet Lab, Washington, DC USA
关键词
D O I
10.1176/appi.ajp.163.1.48
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Objective: The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder. Method: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f(1)Bmax/K-d) was determined by using positron emission tomography with the radiotracer [C-11] McN 5652 and metabolite-corrected arterial input functions. Results: There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. Conclusions: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.
引用
收藏
页码:48 / 51
页数:4
相关论文
共 17 条
[1]   Genetics of the serotonergic system in suicidal behavior [J].
Arango, V ;
Huang, YY ;
Underwood, MD ;
Mann, JJ .
JOURNAL OF PSYCHIATRIC RESEARCH, 2003, 37 (05) :375-386
[2]   Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene [J].
Caspi, A ;
Sugden, K ;
Moffitt, TE ;
Taylor, A ;
Craig, IW ;
Harrington, H ;
McClay, J ;
Mill, J ;
Martin, J ;
Braithwaite, A ;
Poulton, R .
SCIENCE, 2003, 301 (5631) :386-389
[3]  
Frankle WG, 2004, J NUCL MED, V45, P682
[4]   Serotonin transporter genetic variation and the response of the human amygdala [J].
Hariri, AR ;
Mattay, VS ;
Tessitore, A ;
Kolachana, B ;
Fera, F ;
Goldman, D ;
Egan, MF ;
Weinberger, DR .
SCIENCE, 2002, 297 (5580) :400-403
[5]   A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity [J].
Heinz, A ;
Jones, DW ;
Mazzanti, C ;
Goldman, D ;
Ragan, P ;
Hommer, D ;
Linnoila, M ;
Weinberger, DR .
BIOLOGICAL PSYCHIATRY, 2000, 47 (07) :643-649
[6]   Serotonin transporter promoter and intron 2 polymorphisms: Relationship between allelic variants and gene expression [J].
Hranilovic, D ;
Stefulj, J ;
Schwab, S ;
Borrmann-Hassenbach, M ;
Albus, M ;
Jernej, B ;
Wildenauer, D .
BIOLOGICAL PSYCHIATRY, 2004, 55 (11) :1090-1094
[7]  
Hu XZ, 2004, BIOL PSYCHIAT, V55, p191S
[8]   Prediction of dopamine transporter binding availability by genotype: A preliminary report [J].
Jacobsen, LK ;
Staley, JK ;
Zoghbi, S ;
Seibyl, JP ;
Kosten, TR ;
Innis, RB ;
Gelernter, J .
AMERICAN JOURNAL OF PSYCHIATRY, 2000, 157 (10) :1700-1703
[9]   A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical finding in major depression and suicide [J].
Mann, JJ ;
Huang, JY ;
Underwood, MD ;
Kassir, SA ;
Oppenheim, S ;
Kelly, TM ;
Dwork, AJ ;
Arango, V .
ARCHIVES OF GENERAL PSYCHIATRY, 2000, 57 (08) :729-738
[10]  
Mann JJ, 1999, NEUROPSYCHOPHARMACOL, V21, pS99, DOI 10.1038/sj.npp.1395364