Associations between a locus downstream DRD1 gene and cerebrospinal fluid dopamine metabolite concentrations in psychosis. (21st April 2016)

• Record Type: Journal Article
• Authors: Andreou, Dimitrios; Söderman, Erik; Axelsson, Tomas; Sedvall, Göran C.; Terenius, Lars; Agartz, Ingrid; Jönsson, Erik G.
• Is Part Of: Neuroscience letters. Volume 619(2016)
• Page Start: 126
• Page End: 130
• Publication Date: 2016-04-21
• Subjects: HVA homovanillic acid -- DRD2 dopamine receptor D2 gen -- CSF cerebrospinal fluid -- CNS central nervous system -- DRD1 dopamine receptor D1 gene -- DRD3 dopamine receptor D3 gene -- DRD4 dopamine receptor D4 gene -- DRD5 dopamine receptor D5 gene -- SNPs single nucleotide polymorphisms; Schizophrenia -- Psychiatric genetics -- Homovanillic acid (HVA) -- Dopamine receptor D1 gene (DRD1); Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.03.005
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Dopamine receptor D1 gene variation is significantly associated with cerebrospinal fluid homovanillic acid. The significant associations are restricted to psychotic patients. The results support the dopamine hypothesis of schizophrenia. Abstract: Dopamine activity, mediated by the catecholaminergic neurotransmitter dopamine, is prominent in the human brain and has been implicated in schizophrenia. Dopamine targets five different receptors and is then degraded to its major metabolite homovanillic acid (HVA). We hypothesized that genes encoding dopamine receptors may be associated with cerebrospinal fluid (CSF) HVA concentrations in patients with psychotic disorder. We searched for association between 67 single nucleotide polymorphisms (SNPs) in the five dopamine receptor genes i.e., DRD1, DRD2, DRD3, DRD4 and DRD5, and the CSF HVA concentrations in 74 patients with psychotic disorder. Nominally associated SNPs were also tested in 111 healthy controls. We identified a locus, located downstream DRD1 gene, where four SNPs, rs11747728, rs11742274, rs265974 and rs11747886, showed association with CSF HVA concentrations in psychotic patients. The associations between rs11747728, which is a regulatory region variant, and rs11742274 with HVA remained significant after correction for multiple testing. These associations were restricted to psychotic patients and were absent in healthy controls. The results suggest that the DRD1 gene is implicated in the pathophysiology of psychosis and support the dopamine hypothesis of schizophrenia.