Dopamine D4 receptor hypoxia sensitivity and child psychiatric disorders

Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent child psychiatric problems with a complex genetic and environmental background. According to the prevailing view, main factors of the disorder are prefrontal dopamine deficiency and incomplete central dopaminergic functioning. Twin studies suggest substantial heritability in the background of the disease, and the studied candidate genes involve components of the dopamine system. Moreover, various noxious pre- and perinatal environmental impacts have been implicated in the pathogenesis of ADHD. Here we review experimental results from epidemiological, tissue and animal studies that assigned a causal role to fetal hypoxia in the development of ADHD and pointed out that the dopaminergic neurotransmission is sensitive to hypoxia. Allelic variants of the D4 dopamine receptor (DRD4) are well characterized risk factors of ADHD. Recently we have reported that hypoxia enhanced the promoter activity of DRD4 gene several fold. These observations suggest that the effect of hypoxia on the dopaminergic neurotransmission might be an important factor in the pathomechanism of ADHD.