Characterizing the metabolomic signature of attention-deficit hyperactivity disorder in twins

被引:6
|
作者
Swann, J. R. [1 ,2 ]
Heijtz, R. Diaz [3 ]
Mayneris-Perxachs, J. [4 ,5 ]
Arora, A. [6 ,7 ]
Isaksson, J. [6 ,8 ]
Bolte, S. [6 ,9 ,10 ]
Tammimies, K. [6 ,7 ]
机构
[1] Univ Southampton, Fac Med, Sch Human Dev & Hlth, Southampton, England
[2] Imperial Coll London, Fac Med, Dept Metab Digest & Reprod, London, England
[3] Karolinska Inst Reg Stockholm, Dept Neurosci, Stockholm, Sweden
[4] Girona Biomed Res Inst, Dept Diabet Endocrinol & Nutr, Girona, Spain
[5] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid, Spain
[6] Karolinska Inst Reg Stockholm, Ctr Neurodev Disorders KIND, Ctr Psychiat Res, Dept Womens & Childrens Hlth, Stockholm, Sweden
[7] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Region Stockhol, Sweden
[8] Uppsala Univ, Dept Med Sci, Child & Adolescent Psychiat Unit, Uppsala, Sweden
[9] Curtin Univ, Curtin Sch Allied Hlth, Curtin Autism Res Grp, Perth, WA, Australia
[10] Stockholm Hlth Care Serv, Child & Adolescent Psychiat, Stockholm, Region Stockhol, Sweden
基金
瑞典研究理事会; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
Attention deficit hyperactivity disorder; ADHD; Metabolomics; Gut microbiota; Microbial metabolites; Hippurate; Twin study; DOUBLE-BLIND; DEFICIT/HYPERACTIVITY DISORDER; BENZOATE; ADHD; EFFICACY; ADULTS;
D O I
10.1016/j.neuropharm.2023.109562
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Emerging evidence implicate the gut microbiota as a potential susceptibility factor in attention-deficit hyper-activity 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 meta-bolism. 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)-quinoli-none, 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.This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".
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页数:9
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