Neurodevelopmental disorders are conditions that affect the brain both physically and/or functionally. While these disorders are currently understood to be a result of genetic variation, environmental conditions, and chemical exposures, none of the presented causations alone can account for neurodevelopmental etiology. The group believed to be most susceptible to the acquisition of neurodevelopmental disorders is those found in their early-life phase, due to their overall exponential growth and plasticity. To have a further understanding of the early life as well as early-life factors that could contribute towards neurodevelopmental fluctuations, the early-life exposome is an area of study that requires further analysis. Chapter 1 reflects on all of the components that encompass the exposome and how the application of liquid chromatography-mass spectrometry (LC-MS) coupled to data mining for targets of neurodevelopmental concern can further map causations for neurodevelopmental disorders, as well as the early-life human exposome.In Chapter 2, a list of 250 chemicals with a high potential to be neuroactive (ENRICH list) was curated and then utilized to develop a highly potential neuroactive compound tandem mass spectrometry (MS/MS) database. All 250 chemicals were processed via human S9 liver fraction to synthesize the phase I metabolites of all target compounds. A MS/MS database consisting of 274 chemical entries was created, with 94 being found on the ENRICH list and 182 metabolites. In Chapter 3, the validation of the neuroactive MS/MS compound database was performed through in vivo experimentation. All the chemicals in the ENRICH list were administered to mice to determine the biological significance that the database has on the analysis of a living being. Of the original 274 database entries, 106 were found to be present in the urine of mice. Chapters 2 and 3, in combination, help further close the compound annotation bottleneck associated with mass spectrometry while providing evidence of relevance in living beings. In Chapter 4, the urine of children between the ages of 0-5 years old was analyzed in an untargeted and targeted LC-MS workflow. Using the untargeted workflow, a total of 85 different compounds were found to be significant to the children with respect to their household income. The targeted workflow revealed that 15 chemicals found in the neuroactive compound database were also present in the urine of children based upon household income. Altogether, this work provided insights into the exploration of the early-life exposome and how to trace chemicals of neuroactive concern via LC-MS.
Taylor Teitelbaum (Fri,) studied this question.