TY - JOUR
T1 - Maternal Serotonin Levels Are Associated With Cognitive Ability and Core Symptoms in Autism Spectrum Disorder
AU - Montgomery, Alicia K.
AU - Shuffrey, Lauren C.
AU - Guter, Stephen J.
AU - Anderson, George M.
AU - Jacob, Suma
AU - Mosconi, Matthew W.
AU - Sweeney, John A
AU - Turner, J. Blake
AU - Sutcliffe, James S.
AU - Cook, Edwin H.
AU - Veenstra-VanderWeele, Jeremy
N1 - Funding Information:
Funding relevant to this work included National Institutes of Health (NIH) HD055751, MH094604, MH016434, the National Center for Research Resources (NCRR)/NIH, Vanderbilt Clinical and Translational Science Award (CTSA) grant 5UL1 RR024975, the New York State Psychiatric Institute, and the Mortimer D. Sackler, MD, Foundation.
Publisher Copyright:
© 2018 American Academy of Child and Adolescent Psychiatry
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - 5-HT
KW - autism spectrum disorder
KW - hyperserotonemia
KW - maternal
KW - serotonin
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U2 - 10.1016/j.jaac.2018.06.025
DO - 10.1016/j.jaac.2018.06.025
M3 - Article
C2 - 30392628
AN - SCOPUS:85055916636
SN - 0890-8567
VL - 57
SP - 867
EP - 875
JO - Journal of the American Academy of Child Psychiatry
JF - Journal of the American Academy of Child Psychiatry
IS - 11
ER -