Thesis defense Sabrina Hanswijk (Donders series 542)

10 May 2022

Promotors: Prof. dr. J.K. Buitelaar, Prof. dr. J.R. Homberg
Co-promotors: Dr. M. Spoelder-Merkens, Dr. S.M. Kolk

Maternal Serotonin System and Offspring Risk for Neuropsychiatric Disorders

Neuropsychiatric disorders, such as ADHD, ASD, depression, and anxiety, are among the leading causes of burden worldwide. However, effective treatment strategies are often lacking. While a disrupted serotonin (5-hydroxy-tryptamine, 5-HT) system is one of the key pathophysiological mechanisms underlying these disorders, literature is inconsistent regarding the direction of the specific changes. Contradictory 5-HTergic roles might be explained by the dual role of 5-HT, being a neurotrophic factor during neurodevelopment and a neurotransmitter in the course of adulthood. At the time of embryonic development, 5-HT plays a crucial role as neurotrophic factor and is involved in many processes including neurogenesis, neural migration, and circuit development. Indeed, most of the neuropsychiatric disorders have been suggested to be associated with disturbances in such neurodevelopmental processes. Before the fetal brain is capable of synthesizing 5-HT itself, maternal platelets and/or placental 5-HT synthesis serve as an important source. Moreover, the maternal 5-HT system seems to be associated with maternal care quality. Early maternal care, in turn, may play a role in the pathophysiology of neuropsychiatric disorders as well. As a consequence, factors affecting maternal and placental 5-HTergic systems can have substantial effects on offspring’s early brain development and behavior. Insights into how such factors influence the fetal 5-HTergic system may advance our understanding of the aetiology and pathogenetic processes underlying several neuropsychiatric disorders. In this thesis, I aimed to investigate whether factors affecting the maternal 5-HT system provide novel insights into the etiology of the neuropsychiatric disorders ADHD, ASD, depression and anxiety disorders.