Impact of maternal serotonin levels on neurodevelopment

Jeremy Veenstra-VanderWeele and colleagues previously demonstrated in mice that the maternal serotonin transporter (SERT) Ala56 genotype — but not embryo genotype — affected placental and forebrain serotonin (5-HT) levels, as well as thalamocortical projections in offspring1.

They next wanted to explore whether these rodent findings are relevant to ASD. To do so, they used whole blood 5-HT as a surrogate marker of the maternal 5-HT system in an existing sample (from the University of Illinois at Chicago's Autism Center of Excellence [UIC-ACE]2) of 181 children with ASD, 99 fathers and 119 mothers. Exploratory regression analyses demonstrated that a broad range of phenotypic measures were associated with maternal, but not paternal or proband, 5-HT levels. Separating the probands into three ASD subgroups defined by severity across seven variables (including the Autism Diagnostic Interview-Revised [ADI-R] domains, Autism Diagnostic Observation Schedule [ADOS] severity scores, nonverbal intelligence quotient and a composite of the Vineland Adaptive Behavior Scales) demonstrated significant differences in maternal, but not paternal or proband, 5-HT levels across the three subgroups, with lowest maternal blood 5-HT levels present in the highest severity ASD group. While such results are intriguing, it is not possible in this group of affected children to ascertain whether maternal 5-HT is specifically relevant in a subgroup of ASD or whether maternal 5-HT is a marker of general developmental risk in the overall population.

To address this issue, Veenstra-VanderWeele and colleagues plan to: 1) replicate and extend the association of maternal blood 5-HT levels in banked blood samples and proband phenotypes from two Simons Simplex Collection sites (UIC-ACE and Vanderbilt University, n=281); and 2) explore the relationship between 5-HT levels in previously collected placental and umbilical cord blood samples and neurodevelopmental outcomes in a South African cohort.