Genetic Risk Factors for Depression in Alzheimer´s Disease Patients
Sonke Arlt, Cuneyt Demiralay, Bjorn Tharun, Olga Geisel, Niels Storm, Martin Eichenlaub, Jan T. Lehmbeck, Klaus Wiedemann, Boris Leuenberger and Holger Jahn
Affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Building W 37, 20246 Hamburg, Germany.
Objective: Alzheimer´s Disease (AD) is often associated with depressive symptoms developing at any time before
and after AD onset. The aetiology of depression in AD has not sufficiently been characterized, but biological aspects
due to neurodegeneration and/ or genetic risk factors may play a plausible role and may distinguish it from common depressive
Method: To investigate the possible relationship between genetic risk factors and depression in AD, we assessed genetic
polymorphisms reported to be associated with depression (MAOA VNTR, ACE 288bp Insertion/ Deletion, 5HTTLPR,
COMT Val158Met, BDNF Val66Met, TPH1 A218C, HTR2A T102C, P2RX7 Q460R, FKBP5 rs1360780 and CRHR1
rs242941) in a cross-sectional study on 246 AD patients with or without clinically significant major depressive disorder
(MDD) according to DSM-IV.
Results: Significant associations between AD and MDD have been found for three polymorphisms mainly in females
(TPH1 A218C, MAOA VNTR and BDNF Val66Met) and one polymorphism in the total population only (FKBP5
rs1360780). There was an increased risk of having MDD in homozygous female carriers of the TPH1 A-allele (odds ratio:
4.35) and homozygous carriers of the MAOA VNTR low activity allele 3R (odds ratio: 3.37).
Conclusion: We detected allelic or genotypic associations of MAOA, TPH1, FKBP5 and BDNF in clinically significant
MDD in AD. Odds-ratios were generally higher in female AD-patients, which might be due to the composition of the
study population. Further studies on the neurotransmitter systems affected by the genetic polymorphisms found to be associated
with MDD in AD may help to elucidate the underlying pathomechanisms of MDD.
Keywords: Alzheimer´s Disease, Comorbidity, Dementia, Genetic Polymorphism, Genetic Risk Factor, Major Depression
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