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Characterizing the ...
Characterizing the metabolomic signature of attention-deficit hyperactivity disorder in twins
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Swann, J. R. (författare)
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- Diaz Heijtz, R. (författare)
- Karolinska Institutet
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Mayneris-Perxachs, J. (författare)
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- Arora, A. (författare)
- Karolinska Institutet
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- Isaksson, Johan (författare)
- Karolinska Institutet,Uppsala universitet,Barn- och ungdomspsykiatri,Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women’s and Children’s Health, Karolinska Institutet, Region Stockholm, Stockholm, Sweden
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- Bölte, S. (författare)
- Karolinska Institutet
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- Tammimies, K. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 234
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Emerging evidence implicate the gut microbiota as a potential susceptibility factor in attention-deficit hyperactivity disorder (ADHD), a common multifactorial neurodevelopmental condition. However, little is known about the biochemical signature of ADHD, including the metabolic contribution of the microbiota via the gut-brain axis, and the relative contribution of genetics and environmental factors. Here, we perform unbiased metabolomic profiling of urine and fecal samples collected from a well-characterized Swedish twin cohort enriched for ADHD (33 ADHD, 79 non-ADHD), using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. Our results highlight sex-specific patterns in the metabolic phenotype of individuals with ADHD. Specifically, the urine profile of males, but not females, with ADHD was characterized by greater excretion of hippurate, a product of microbial-host co-metabolism that can cross the blood-brain-barrier with bioactivity of potential relevance to ADHD. This trans-genomic metabolite was also negatively correlated with IQ in males and was significantly correlated with fecal metabolites associated with gut microbial metabolism. The fecal profile of ADHD individuals was characterized by increased excretion of stearoyl-linoleoyl-glycerol, 3,7-dimethylurate, and FAD and lower amounts of glycerol 3-phosphate, thymine, 2(1H)-quinolinone, aspartate, xanthine, hypoxanthine, and orotate. These changes were independent of ADHD medication, age, and BMI. Furthermore, our specific twins' models revealed that many of these gut metabolites had a stronger genetic influence than environmental. These findings suggest that metabolic disturbances in ADHD, involving combined gut microbial and host metabolic processes, may largely derive from gene variants previously linked to behavioral symptoms in this disorder.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Nyckelord
- ADHD
- Attention deficit hyperactivity disorder
- Gut microbiota
- Hippurate
- Metabolomics
- Microbial metabolites
- Twin study
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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