title: Allelic variation at the A218C tryptophan hydroxylase polymorphism influences agitation and aggression in Alzheimer's disease.
abstract: The behavioural and psychological symptoms of dementia are common, distressing to carers, and directly linked to the requirement for institutional care. Symptoms of aggression and agitation are particularly difficult for carers to tolerate. The origin of these features is unclear although genetic and environmental modification of pre-frontal serotonergic circuitry which regulates the control of negative emotions is proposed. Following the suggestion that the A218C intronic polymorphism of the tryptophan hydroxylase gene influences aggression and anger in non-demented individuals, we tested the influence of A218C on symptoms of agitation/aggression in 396 Alzheimer's disease patients using the Neuropsychiatric Inventory. Overall, 50% of participants experienced agitation/aggression in the month prior to interview. It was observed that male patients with a history of agitation/aggression were more likely to possess C-containing genotypes (P = 0.044, OR = 1.65, CI = 0.98-2.76). We conclude that aggression in male subjects with Alzheimer's disease may be genetically linked to polymorphic variation at the tryptophan hydroxylase gene.
authors.affiliation: Department of Geriatric Medicine, Whitla Medical Building, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. david.craig@qub.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hart
authors.forename: Robin
authors.initials: R
authors.lastname: Carson
authors.forename: Stephen P
authors.initials: SP
authors.lastname: McIlroy
authors.forename: A Peter
authors.initials: AP
authors.lastname: Passmore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000502:physiology*; D000409:Alanine / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003545:Cysteine / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D012737:Sex Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: D014365:Tryptophan Hydroxylase; D003545:Cysteine; D000409:Alanine