Alicia K Montgomery1, Lauren C Shuffrey2, Stephen J Guter3, George M Anderson4, Suma Jacob5, Matthew W Mosconi6, John A Sweeney7, J Blake Turner8, James S Sutcliffe9, Edwin H Cook3, Jeremy Veenstra-VanderWeele10. 1. Columbia University Medical Center, New York, NY, and the New York State Psychiatric Institute, New York, NY; Center for Autism and the Developing Brain, New York-Presbyterian Hospital, White Plains, NY. 2. New York State Psychiatric Institute, New York, NY, and the Center for Autism and the Developing Brain, New York-Presbyterian Hospital, White Plains, NY. They are also with the Sackler Institute for Developmental Psychobiology; Columbia University Medical Center, New York, NY. 3. Institute for Juvenile Research at the University of Illinois at Chicago, IL. 4. Child Study Center, Yale University, New Haven, CT. 5. University of Minnesota, Minneapolis. 6. Kansas Center for Autism Research and Training, Overland Park. He is also with the Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies at the University of Kansas, Lawrence. 7. University of Cincinnati, Ohio. 8. Columbia University Medical Center, New York, NY, and the New York State Psychiatric Institute, New York, NY. 9. Vanderbilt University Medical Center, Nashville, TN. 10. New York State Psychiatric Institute, New York, NY, and the Center for Autism and the Developing Brain, New York-Presbyterian Hospital, White Plains, NY. They are also with the Sackler Institute for Developmental Psychobiology; Columbia University Medical Center, New York, NY. Electronic address: jeremy.veenstra@nyspi.columbia.edu.
Abstract
OBJECTIVE: The serotonin (5-hydroxytryptamine [HT]) system has long been implicated in autism spectrum disorder (ASD). Whole-blood 5-HT level (WB5-HT) is a stable, heritable biomarker that is elevated in more than 25% of children with ASD. Recent findings indicate that the maternal 5-HT system may influence embryonic neurodevelopment, but maternal WB5-HT has not been examined in relation to ASD phenotypes. METHOD: WB5-HT levels were obtained from 181 individuals (3-27 years of age) diagnosed with ASD, 99 of their fathers, and 119 of their mothers. Standardized assessments were used to evaluate cognitive, behavioral, and language phenotypes. RESULTS: Exploratory regression analyses found relationships between maternal WB5-HT and nonverbal IQ (NVIQ), Autism Diagnostic Interview-Revised (ADI-R) Nonverbal Communication Algorithm scores, and overall adaptive function on the Vineland Adaptive Behavior Scales-II. Latent class analysis identified a three-class structure in the assessment data, describing children with low, intermediate, and high severity across measures of behavior, cognition, and adaptive function. Mean maternal WB5-HT differed across classes, with the lowest maternal WB5-HT levels seen in the highest-severity group (Welch F2,46.048 = 17.394, p < .001). Paternal and proband WB5-HT did not differ between classes. CONCLUSION: Maternal WB5-HT is associated with neurodevelopmental outcomes in offspring with ASD. Prospective, longitudinal studies will be needed to better understand the relationship between the function of the maternal serotonin system during pregnancy and brain development. Further studies in animal models may be able to reveal the mechanisms underlying these findings.
OBJECTIVE: The serotonin (5-hydroxytryptamine [HT]) system has long been implicated in autism spectrum disorder (ASD). Whole-blood 5-HT level (WB5-HT) is a stable, heritable biomarker that is elevated in more than 25% of children with ASD. Recent findings indicate that the maternal 5-HT system may influence embryonic neurodevelopment, but maternal WB5-HT has not been examined in relation to ASD phenotypes. METHOD:WB5-HT levels were obtained from 181 individuals (3-27 years of age) diagnosed with ASD, 99 of their fathers, and 119 of their mothers. Standardized assessments were used to evaluate cognitive, behavioral, and language phenotypes. RESULTS: Exploratory regression analyses found relationships between maternal WB5-HT and nonverbal IQ (NVIQ), Autism Diagnostic Interview-Revised (ADI-R) Nonverbal Communication Algorithm scores, and overall adaptive function on the Vineland Adaptive Behavior Scales-II. Latent class analysis identified a three-class structure in the assessment data, describing children with low, intermediate, and high severity across measures of behavior, cognition, and adaptive function. Mean maternal WB5-HT differed across classes, with the lowest maternal WB5-HT levels seen in the highest-severity group (Welch F2,46.048 = 17.394, p < .001). Paternal and proband WB5-HT did not differ between classes. CONCLUSION: Maternal WB5-HT is associated with neurodevelopmental outcomes in offspring with ASD. Prospective, longitudinal studies will be needed to better understand the relationship between the function of the maternal serotonin system during pregnancy and brain development. Further studies in animal models may be able to reveal the mechanisms underlying these findings.
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