Investigation of association of serotonin transporter and monoamine oxidase-A genes with Alzheimer's disease and depression in the VITA study cohort: a 90-month longitudinal study.
Alzheimer's disease (AD) and depression (DE) are common psychiatric disorders strongly intertwined with one another. Nevertheless, etiology and early diagnosis of the disorders are still elusive. Several genetic variations have been suggested to associate with AD and DE, particularly in genes involved in the serotonergic system such as the serotonin transporter (SERT/SLC6A4), responsible for the removal from the synaptic cleft, and the monoamine-oxidase-A (MAOA), responsible for the presynaptic degradation of serotonin. Here, we attempt to characterize this pleiotropic effect for the triallelic SERT gene-linked polymorphic region (5HTTLPR) and for the MAOA-uVNTR, in participants in the Vienna-Transdanube-Aging (VITA)-study. The VITA-study is a community-based longitudinal study following a birth cohort (75 years old at baseline examination, n = 606) from Vienna for a period of 90 months with a regular follow-up interval of 30 months. Our main finding, confirming previous reports, is that the 5HTTLPR S-allele is a risk allele for DE (OR = 1.55 CI 95% 1.03-2.32) and its carriers had a steeper increase in SGDS sum score. No association to AD was found. MAOA-uVNTR did not associate with either AD or DE. However, in AD MAOA-uVNTR S-allele carriers a steeper increase of HAMD and STAI1 sum scores (P < 0.05) was observed. Although the VITA-study cohort is rather small with low power to detect gene alterations, the uniqueness of this very thoroughly investigated and homogenous cohort strengthens the results through exceptional data collection. Still, reinvestigation in a larger cohort similar to this, as well as a meta-analysis, is important to confirm these results.
Interdisciplinary Centre for Clinical Research (IZKF), University Hospital of Würzburg, Würzburg, Germany.
Claus-Jürgen
CJ
Scholz
Susanne
S
Jungwirth
Walter
W
Danielczyk
Heike
H
Weber
Ildiko
I
Wichart
Karl Heinz
KH
Tragl
Peter
P
Fischer
Peter
P
Riederer
Jürgen
J
Deckert
Edna
E
Grünblatt
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase
Alzheimer's disease; MAOA; SLC6A4; depression; polymorphism; serotonin transporter