Browsing by Author "Laakso, Hanna"

Autism spectrum disorders (ASD) are a heterogenous group of disorders, with the core symptoms appearing as different levels of difficulties in communicative and social skills, but there are a number of neuroanatomical, neurotransmitter related and gastrointestinal aberrations that have also been linked to the disorder. The etiology of ASD is not very well known, but in addition to a strong genetic background, current research shows that prenatal factors might play a significant role in the development of the disorder. In this review, the proposed mechanisms of action of some prenatal risk factors are discussed in the light of current research. Many other risk factors have repeatedly been linked to ASD in empirical studies as well, but this review focuses on the possible paths through which valproic acid (VPA), thalidomide and vitamin D might be connected to the development of ASD. In addition, the retinoic acid-estradiol theory is presented, which aims to explain the link between ASD and a number of risk factors. Several proposed mechanisms of action have been formed for each of the discussed risk factors, but only some of them are presented in this review. VPA’s role in ASD is examined through the most widely used animal model of ASD (prenatally VPA-induced rats), and the role in the etiology of human ASD through proposed aberrations of both ammonium and folate metabolism caused by prenatal VPA exposure. Prenatal exposure to thalidomide might influence the functioning of the protein cereblon, which according to research is linked to the functioning of ion channels and mRNA activation in certain parts of the brain. The effects of Vitamin D deficiency are theorized to be connected to ASD through the human serotonergic system. This is explained through two genes (TPH1 and TPH2), which hold a crucial role in serotonin synthesis, and Vitamin D is known to affect the expression of these genes. According to the retinoic acid-estradiol theory, the balance between three endogenous chemical substances (retinoic acid [RA] estradiol and human alpha-fetoprotein [HAFP]) have an essential effect on fetal development: RA on certain genes’ expression, estradiol on neural defeminization processes and HAFP by protecting against harmful effects of both RA and estradiol. According to the theory, prenatal risk factors can be divided to promoters of RA-sensitive growth (VPA), inhibitors of HAFP production (thalidomide, ethanol, the ToRCH [toxoplasmosis-rubella-cytomegalovirus-herpes] infection family, interleukins) and promoters of estrogen-sensitive growth (hypothyroidism, iodine deficiency). Under the umbrella term “ASD” lies a wide variety of disorders with big differences in the level of severity and the ways of showing symptoms. In the light of today’s empirical knowledge, there is no certainty weather or not ASD is one single disorder or are there actually several completely unrelated disorders which are just arbitrarily grouped together.