Placenta-derived hypo-serotonin situations in the developing forebrain inhibits dopaminergic fiber development, resulting in ADHD

Kohji Sato
2016 Journal of brain science  
Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurobehavioral disorders. Converging evidence implicates dopamine neurotransmission is involved in the phathophysiology of ADHD. PET studies in adult medication naïve patients found that ADHD is associated with reduced dopamine transporter (DAT), indicating that dopaminergic fibers are reduced in ADHD brains. On the other hand, hypo-serotonin situations in pregnancy are also considered to be risk factors for ADHD.
more » ... ver, the relationship between the hypo-serotonin situations and the reduction of dopaminergic fibers is largely unknown. Recently, it has been reported that placenta-derived serotonin is the main source in embryonic day (E) 10-15 mouse forebrain, after that period, the serotonergic fibers start to supply serotonin into the forebrain. Interestingly, Journal of Brain Science, June 30, 2016,Vol.46 21 dopaminergic fibers also extend rapidly in E10-15. In addition, serotonin is known to promote neurite outgrowth via serotonin receptor 7 (5-HTR7). Thus, I speculate that hypo-serotonin situations in E10-15 might impair the dopaminergic axon development, resulting in mal-growth of dopamine fibers in the forebrain. The hypothesis is as follows. Various factors, such as inflammation, dysfunction of the placenta, together with genetic predispositions cause a decrease of placenta-derived serotonin levels. The decrease of placenta-derived serotonin levels leads to hypo-serotonergic situations in the forebrain of the fetus. The paucity of serotonin in the forebrain leads to mal-growth of dopaminergic fibers. The paucity of dopaminergic fibers in the forebrain causes ADHD.
doi:10.20821/jbs.46.0_20 fatcat:wqe4o6bs2fakxpp7vkhdyf3zbm