NR4A2: effects of an "orphan" receptor on sustained attention in a schizophrenic population

NR4A2 (nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence of NR4A2 gene in the performance of schizophrenia (SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs in NR4A2 gene: rs1150143 (C/G), rs1150144 (A/G), rs834830 (A/G), rs1466408 (T/A), and rs707132 (A/G). We also analyzed the influence of its haplotypes (frequency>5%). To examine sustained attention, all the individuals completed the Degraded Stimulus Continuous Performance Test. We evaluated "hits," "reaction time," "sensibility a," and "false alarms." In the schizophrenic group, recessive genotypes of rs1150143, rs1150144, rs834830, and rs707132 were associated with a worse performance. SZ subjects who carried GGGTG haplotype showed less hits (P<.004), lower sensibility a scores (P<.009), and a higher reaction time (P=.013). We observed a sex effect of the gene: genotype and haplotype associations were only present in the male group. We conclude that NR4A2 gene is involved in attentional deficits of SZ patients, modifying hits, sensibility a, and reaction time.