Associations between a locus downstream DRD1 gene and cerebrospinal fluid dopamine metabolite concentrations in psychosis
2016 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 619, 126-130 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
2016. Vol. 619, 126-130 p.
Schizophrenia, Psychiatric genetics, Homovanillic acid (HVA), Dopamine receptor D1 gene (DRD1)
IdentifiersURN: urn:nbn:se:uu:diva-297116DOI: 10.1016/j.neulet.2016.03.005ISI: 000374624000020PubMedID: 26957229OAI: oai:DiVA.org:uu-297116DiVA: diva2:941154
FunderSwedish Research Council, K2007-62X-15077-04-1Swedish Research Council, K2008-62P-20597-01-3Swedish Research Council, K2010-62X-15078-07-2Swedish Research Council, K2012-61X-15078-09-3Stockholm County CouncilThe Karolinska Institutet's Research FoundationKnut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research Council