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Article type: Research Article
Authors: Middle, Fionaa; | Pritchard, Antonia L.a; b; *; | Handoko, Herlinab | Haque, Sayeedc | Holder, Rogerc | Bentham, Peterc | Lendon, Corinne L.a; b
Affiliations: [a] Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Birmingham, UK | [b] Molecular Psychiatry Group, Genetics and Population Health Division, Queensland Institute of Medical Research, Herston, Brisbane, Australia | [c] Division of Neuroscience, Department of Psychiatry, The Barberry, University of Birmingham, Edgbaston, Birmingham, UK
Correspondence: [*] Correspondence to: Antonia L. Pritchard, Molecular Psychiatry Group, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, 4006, Australia. Tel.: +61 (0)7 33620323; Fax: +61 (0)7 38453508; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Alzheimer's disease (AD) patients commonly suffer from behavioral and psychological symptoms of dementia (BPSD). Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD patients with psychosis. In this study, we analyzed NRG1 variants in AD patients with and without psychosis. Our large cohort of 399 probable AD patients had longitudinal information on the BPSD, which was used to dichotomize patients into whether they had ever suffered from psychotic symptoms within the study period. The NRG1 single nucleotide polymorphisms rs3924999, rs35753505 (SNP8NRG221533) and the microsatellites 478B14-848 and 420M9-1395 were investigated for association with psychosis using genotype, allele, and haplotype analyses. No associations were found between any of these variants or haplotypic combinations with delusions, hallucinations, psychosis, or elation/mania in our cohort. Positive associations with polymorphisms and haplotype combinations of NRG1 have been reported in psychiatric disorders. One previous study found an association with psychosis in AD, with a SNP outside the haplotype block first reported for association with schizophrenia. We found no association with any of these variants in our cohort. Further investigations of this region on chromosome 8 are clearly required, with replication in different large longitudinal cohorts.
Keywords: Alzheimer's disease, BPSD, haplotype, neuregulin 1, psychosis
DOI: 10.3233/JAD-2010-1405
Journal: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 561-567, 2010
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