Metabolite-Autism Symptom Associations Mediated by Amygdala-Frontal Resting State Connectivity
Poster No:
436
Submission Type:
Abstract Submission
Authors:
Sofronia Ringold1,2, Aditya Jayashankar1,2, Jennifer Labus3,4,5, Emily Kilroy1,2, Christiana Butera1,2, Swapna Mahurkar-Joshi3,4,5, Skylar Tanartkit3,4,5, Arpana Gupta3,4,5, Emeran Mayer3,4,5, Lisa Aziz-Zadeh1,2
Institutions:
1Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, 2Brain and Creativity Institute, University of Southern California, Los Angeles, CA, 3Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine, Los Angeles, CA, 4Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, Los Angeles, CA, 5Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
First Author:
Sofronia Ringold
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Co-Author(s):
Aditya Jayashankar
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Jennifer Labus, PhD
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Emily Kilroy, PhD
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Christiana Butera
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Swapna Mahurkar-Joshi
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Skylar Tanartkit
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Arpana Gupta, PhD
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Emeran Mayer, MD, PhD
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Oppenheimer Center for the Neurobiology of Stress and Resilience, David Geffen School of Medicine|Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine|Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles
Los Angeles, CA|Los Angeles, CA|Los Angeles, CA
Lisa Aziz-Zadeh
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Chan Division of Occupational Science and Occupational Therapy, University of Southern California|Brain and Creativity Institute, University of Southern California
Los Angeles, CA|Los Angeles, CA
Introduction:
The gut microbiome modulates sensory processing, socio-emotional behavior, and cognition through a bidirectional relationship with the brain, known as the brain-gut-microbiome (BGM) system (Zhu et al., 2017). As cognitive, sensory, social, and gastrointestinal issues are highly prevalent in Autism Spectrum Disorder (ASD), attention has been paid to the role of the BGM system in ASD symptomatology, with many studies reporting abnormal gut profiles compared to healthy controls (Kang et al., 2018; Needham et al., 2021). Preclinical studies have shown that gut metabolites in the tryptophan pathway are associated with sensory, socio-emotional, and cognitive differences characteristic of ASD thus the BGM system, may be related to outcomes in autistic children, such as school performance (Chen et al., 2022; Chernikova et al., 2021; Needham et al., 2022). As sensory processing has a greater impact on academic performance in autistic children than level of intelligence, we posit that gut metabolites are influencing neural activity, subsequently impacting school performance (Butera et al., 2020). Here we focus on resting state functional magnetic resonance imaging (rs-fMRI) in typically developing (TD) and autistic children as established connectivity differences between the groups has been linked to ASD symptom severity which may be linked to school performance (Christian et al., 2022; Khandan Khadem-Reza et al., 2023).
Methods:
Data Collection: 37 TD (M age=12.02 years, 18 males) and 29 autistic children (M age=12.4 years, 22 male) collected a stool sample at home within 24 hours prior to completing a rs-fMRI. Parents completed the Child Behavior Checklist/6-18 to assess school performance (Achenbach & Edelbrock, 1991). Data Analysis: Resting state connectivity between brain regions based on the Detstrieux, Harvard Oxford subcortical and Harvard Ascending Arousal Network Atlases was computed using the functional connectivity toolbox. Untargeted metabolomic profiling on the stool samples were performed by Metabolon Inc. General linear models (GLM) were used to determine if the groups differences and associations between school performance and med-adjusted tryptophan metabolites and functional connectivity, tryptophan metabolite levels, age, sex, body mass index and IQ scores. The R library, mediation, was applied to test whether neural activity mediated the association between metabolite levels and school performance in ASD with age as a covariate.
Results:
There was a significant difference between the groups on school performance (ASD<TD, q<0.01, 5% FDR). GLMs demonstrated a significant difference in functional connectivity between the right orbital sulcus and the left amygdala (ASD<TD, q<0.001) that was associated with abundance of the tryptophan metabolite, oxindolylalanine (q<0.05). In ASD, connectivity in the right orbital sulcus and the left amygdala was negatively correlated with school performance (q<0.05). The right orbital sulcus-the left amygdala connectivity significantly mediated the relationship between oxindolylalanine and school performance (B=1.11, 95% CI:0.10-2.54).
Conclusions:
Previous rs-fMRI research in ASD suggests that decreased connectivity between the amygdala and frontal lobe regions may underlie emotion regulation and sensory sensitivities (Khandan Khadem-Reza et al., 2023). Here we show that this decreased connectivity is also related to lower gut levels of oxindolylalanine and lower school performance. Specifically, our data support the hypothesis that the metabolites in the tryptophan pathway modulate the brain, which in turn affects behavior in ASD. This is the first study to explore the complex interplay between gut metabolites, resting state functional connectivity, and behavioral outcomes in autistic children.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other
Keywords:
Autism
FUNCTIONAL MRI
Other - Metabolites
1|2Indicates the priority used for review
Provide references using author date format
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Chen, Y.-C. (2022). Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism. Brain, behavior, and immunity, 106, 161-178. https://doi.org/10.1016/j.bbi.2022.08.015
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