Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

Abstract

The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [11C] raclopride binding to the D 2 - and D 3 -dopamine receptor and [11C] WAY100635 binding to the serotonin 5-HT 1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D 2/3 and 5-HT 1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D 2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT 1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.