Associations between a locus downstream DRD1 gene and cerebrospinal fluid dopamine metabolite concentrations in psychosis

Axelsson, Tomas (author): Uppsala universitet,Institutionen för medicinska vetenskaper

Sedvall, Goran C. (author): Karolinska Hosp & Inst, HUBIN Project, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden.

(creator_code:org_t)

Elsevier BV, 2016
2016
English.
In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 619, s. 126-130

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Abstract Subject headings

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.

By the author/editor: Andreou, Dimitri ...; Soderman, Erik; Axelsson, Tomas; Sedvall, Goran C ...; Terenius, Lars; Agartz, Ingrid; show more...; Jonsson, Erik G.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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