Homozygous short (SS) genotype-HTTLPR, GG genotype of HTR2A-rs6311 and CC genotype of HTR2A-rs6313 were associated with AD treatment-induced insomnia, while val/met genotype of BDNF-rs6265 and the TT genotype of GSK-3beta-rs5443 reduced it.
Significant association was covered between allelic and recessive models of 5-HT2A T102C and AD (allelic model: <i>p</i> = 0.003, OR [95% CI] = 1.23 [1.07, 1.40]; recessive model: <i>p</i> = 0.03, OR [95% CI] = 1.28 [1.02, 1.59]).
Our study suggests no individual influence of the investigated polymorphisms but a potential combined effect of the 5-HTTLPR L/L and HTR2A T102C C/C genotypes on AD risk.
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.
The strong and robust positive association that was noted between the C allele of HTR2A and psychosis suggests that the HTR2A T102C polymorphism is a significant risk factor for psychosis of AD.
Thus our study, although at preliminary level, suggests that the presence of T allele of the 102T/C polymorphism in patients with Alzheimer's disease is associated with both increased presence of delusion symptoms and treatment-resistance to second generation antipsychotic drugs.
This study suggests a mechanism for the generation of different neuropsychiatric symptoms in AD from a single nucleotide polymorphism with reduced receptor binding in T102C 5-HT2A receptor gene homozygotes correlating with susceptibility to depressive symptoms, whereas the relative preservation of receptor binding in heterozygotes with AD correlating with susceptibility to hallucinations.
The aim of this study was to investigate the association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with the risk of developing dementia and/or psychotic symptoms in a group of sporadic AD patients from Italy.