Interplay between Blood Metabolites and Brain Grey Matter Volume in autism spectrum disorder
Poster No:
351
Submission Type:
Abstract Submission
Authors:
Chia-Wei Lin1, Susan Shur-Fen Gau2
Institutions:
1Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, New City, NY, 2Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
First Author:
Chia-Wei Lin
Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital
New City, NY
Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital
New City, NY
Co-Author:
Introduction:
Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by altered brain structure and function, with two core symptoms: difficulties in social communication and interaction, and restricted, repetitive patterns of behaviors, interests or activities. While its etiology is multifactorial, metabolic alterations are linked to neurodevelopmental changes in ASD (Needham et al., 2021). This study aims to investigate the differential metabolites and metabolic pathways between individuals with ASD and typically developing controls (TDC), assess the relationship between differential blood metabolites and grey matter volume in key brain regions, and explore the role of metabolomic alterations in ASD development.
Methods:
A cohort study integrating blood metabolomics and brain magnetic resonance imaging, comparing individuals of autism spectrum disorder and typically developing controls. Blood untargeted metabolites were performed with ultra-high performance liquid chromatography tandem mass spectrometry, and regional brain grey matter volume was assessed through magnetic resonance imaging via voxel-based morphometry. The primary outcome was the comparison of relative abundance of blood metabolites and metabolic pathways between groups. The comparison of relative abundance was conducted using multivariate analysis (principal components analysis and orthogonal projection to latent structures-discriminant analysis) and univariate analysis (Student's t-test). Metabolic pathway enrichment and topology analysis were conducted for each individual pair-wise comparison, yielding a pathway impact score. The secondary outcome was the correlation between the relative abundance of differential metabolites and grey matter volume in key brain regions, using Pearson's correlation with Benjamini-Hochberg adjustments.
Results:
140 ASD ( mean [SD] age, 13.59 [6.02] years; 115 [82.1%]male) and 52 TDC (mean [SD] age, 14.93 [6.19] years; 36 [69.2%]male) were enrolled. Six metabolic pathways: (1) Arginine and proline metabolism, (2) Glycine, serine, and threonine metabolism, (3) Tryptophan metabolism, (4) Fatty acid biosynthesis, (5) Biosynthesis of unsaturated fatty acids, and (6) Pyruvate metabolism; and five corresponding metabolites: Creatine, L-Tryptophan, Undecanedioic acid, Oleic acid, and S-Lactoylglutathione were upregulated in ASD over TDC (Figure 1). Among them, the Tryptophan metabolism pathway showing the largest impact value (0.14). Elevated blood L-tryptophan relative abundance significantly correlated with reduced grey matter volume in serotonin-related brain regions in autism group, including medial prefrontal cortex (Right, r = -0.199, p = 0.025; Left, r = -0.182, p = 0.041), amygdala (Right, r = -0.228, p = 0.021; Left, r = -0.242, p = 0.021), left hippocampus (r = -0.183, p = 0.041), and right parahippocampus (r = -0.224, p = 0.021), with no such correlations observed in TDC (Figure 2).
·Figure 1 Metabolomics comparison between ASD and TDC
·Figure 2 Correlation of blood tryptophan and regional grey matter volume of serotonin pathway in ASD and TDC
Conclusions:
The study is the first to integrate blood untargeted metabolomics and brain MRI data in patients with ASD. Differential blood metabolites and metabolic pathways were identified, with up-regulated blood tryptophan and tryptophan metabolism showing the largest impact value. Elevated relative abundance of blood tryptophan significant correlated with reduced GM volume in serotonin-related brain regions in ASD, but not in TDC. These regions regulate emotion (Meneses & Liy-Salmeron, 2012), social cognition (Nummenmaa, Seppala, & Putkinen, 2023), perception (Canli & Lesch, 2007), reward (Berger, Gray, & Roth, 2009), and attention (Canli & Lesch, 2007)-functions closely related to symptoms of ASD. Findings suggest that upregulated blood L-tryptophan associated with grey matter volume reductions in social brain network crucial for social-emotional processing in ASD, supporting the role of metabolomic contributions to autism neurodevelopment. This highlights potential therapeutic avenues targeting these metabolites and brain regions.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Novel Imaging Acquisition Methods:
Anatomical MRI
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Autism
MRI
Seretonin
1|2Indicates the priority used for review
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Provide references using APA citation style.
Canli, T., & Lesch, K. P. (2007). Long story short: the serotonin transporter in emotion regulation and social cognition. Nat Neurosci, 10(9), 1103-1109. doi:10.1038/nn1964
Meneses, A., & Liy-Salmeron, G. (2012). Serotonin and emotion, learning and memory. Rev Neurosci, 23(5-6), 543-553. doi:10.1515/revneuro-2012-0060
Needham, B. D., Adame, M. D., Serena, G., Rose, D. R., Preston, G. M., Conrad, M. C., . . . Mazmanian, S. K. (2021). Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biol Psychiatry, 89(5), 451-462. doi:10.1016/j.biopsych.2020.09.025
Nummenmaa, L., Seppala, K., & Putkinen, V. (2023). Molecular Imaging of the Human Emotion Circuit. In P. S. Boggio, T. S. H. Wingenbach, M. L. da Silveira Coelho, W. E. Comfort, L. Murrins Marques, & M. V. C. Alves (Eds.), Social and Affective Neuroscience of Everyday Human Interaction: From Theory to Methodology (pp. 3-21). Cham (CH).