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 disorders. 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.
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 disorders. 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, COMTVal158Met, BDNFVal66Met, TPH1A218C, HTR2AT102C, P2RX7Q460R, FKBP5rs1360780 and CRHR1rs242941) in a cross-sectional study on 246 ADpatients 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 (TPH1A218C, MAOA VNTR and BDNFVal66Met) and one polymorphism in the total population only (FKBP5rs1360780). 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.
Authors: Mayuresh S Korgaonkar; Kaushik Ram; Leanne M Williams; Justine M Gatt; Stuart M Grieve Journal: Hum Brain Mapp Date: 2014-01-22 Impact factor: 5.038
Authors: Ann Kolanowski; Marie Boltz; Elizabeth Galik; Laura N Gitlin; Helen C Kales; Barbara Resnick; Kimberly S Van Haitsma; Amy Knehans; Jane E Sutterlin; Justine S Sefcik; Wen Liu; Darina V Petrovsky; Lauren Massimo; Andrea Gilmore-Bykovskyi; Margaret MacAndrew; Glenna Brewster; Vycki Nalls; Ying-Ling Jao; Naomi Duffort; Danny Scerpella Journal: Nurs Outlook Date: 2017-06-16 Impact factor: 3.250
Authors: Nadia V Harerimana; Yue Liu; Ekaterina S Gerasimov; Duc Duong; Thomas G Beach; Eric M Reiman; Julie A Schneider; Patricia Boyle; Adriana Lori; David A Bennett; James J Lah; Allan I Levey; Nicholas T Seyfried; Thomas S Wingo; Aliza P Wingo Journal: Biol Psychiatry Date: 2021-12-16 Impact factor: 12.810
Authors: Barbara Resnick; Elizabeth Galik; Ann Kolanowski; Kimberly VanHaitsma; Marie Boltz; Shijun Zhu; Jeanette Ellis; Liza Behrens; Karen Eshraghi Journal: J Women Aging Date: 2020-03-06