Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain

Dopamine 2 receptor (DRD2) is of major interest to the pathophysiology of schizophrenia (SCZ) both as a target for antipsychotic drug action as well as a SCZ-associated risk gene. The dopamine 1 receptor (DRD1) is thought to mediate some of the cognitive deficits in SCZ, including impairment of work...

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Veröffentlicht in:Molecular psychiatry 2014-12, Vol.19 (12), p.1258-1266
Hauptverfasser: Kaalund, S S, Newburn, E N, Ye, T, Tao, R, Li, C, Deep-Soboslay, A, Herman, M M, Hyde, T M, Weinberger, D R, Lipska, B K, Kleinman, J E
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Sprache:eng
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Zusammenfassung:Dopamine 2 receptor (DRD2) is of major interest to the pathophysiology of schizophrenia (SCZ) both as a target for antipsychotic drug action as well as a SCZ-associated risk gene. The dopamine 1 receptor (DRD1) is thought to mediate some of the cognitive deficits in SCZ, including impairment of working memory that relies on normal dorsolateral prefrontal cortex (DLPFC) function. To better understand the association of dopamine receptors with SCZ, we studied the expression of three DRD2 splice variants and the DRD1 transcript in DLPFC, hippocampus and caudate nucleus in a large cohort of subjects (~700), including patients with SCZ, affective disorders and nonpsychiatric controls (from 14th gestational week to 85 years of age), and examined genotype-expression associations of 278 single-nucleotide polymorphisms (SNPs) located in or near DRD2 and DRD1 genes. Expression of D2S mRNA and D2S/ D2-long ( D2L ) ratio were significantly increased in DLPFC of patients with SCZ relative to controls ( P
ISSN:1359-4184
1476-5578
DOI:10.1038/mp.2013.165