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Robert A. Sweet, MD; Vishwajit L. Nimgaonkar, MD, PhD; M. Ilyas Kamboh, PhD; Oscar L. Lopez, MD; Feng Zhang, BS; Steven T. DeKosky, MD

Arch Neurol. 1998;55:1335-1340.

Objective  To examine if selected polymorphisms in the dopaminereceptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer disease (AD).

Design  A cohort of patients with AD were longitudinally evaluated for behavioral symptoms and classified with regard to the presence of psychotic symptoms and physical aggression.

Setting  Alzheimer's Disease Research Center.

Patients  Two hundred seventy-five elderly outpatients diagnosed as having probable AD.

Results  Among white patients, psychosis and aggression were both significantly more frequent in DRD1 B2/B2 homozygotes (P<.02), while psychosis was significantly more frequent in DRD3 1/1 or 2/2 homozygotes (P<.05). The joint risk for psychosis due to the DRD1 and DRD3 polymorphisms exceeded the risks due to either locus alone, suggesting an interaction. Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression.

Conclusions  Genetic variation in DRD1 and DRD3 genes may act to modify the course of AD, predisposing to the development of psychotic or aggressive symptoms. Confirmation in other samples of patients with AD is required.

From the Departments of Psychiatry (Drs Sweet, Nimgaonkar, and DeKosky, and Mr Zhang) and Neurology (Drs Lopez and DeKosky), University of Pittsburgh School of Medicine, and the Department of Human Genetics, University of Pittsburgh Graduate School of Public Health (Drs Nimgaonkar and Kamboh), Pittsburgh, Pa.

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