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. 2016 Sep 29;12(1):27.
doi: 10.1186/s12993-016-0112-1.

A non-targeted metabolite profiling pilot study suggests that tryptophan and lipid metabolisms are linked with ADHD-like behaviours in dogs

Jenni Puurunen  1   2 , Sini Sulkama  1   2 , Katriina Tiira  1   2 , Cesar Araujo  1   2 , Marko Lehtonen  3 , Kati Hanhineva  4   5 , Hannes Lohi  6   7
Affiliations
Free PMC article

A non-targeted metabolite profiling pilot study suggests that tryptophan and lipid metabolisms are linked with ADHD-like behaviours in dogs

Jenni Puurunen et al. Behav Brain Funct. .
Free PMC article

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent and multifactorial neuropsychiatric disorder in the human population worldwide. Complex etiology and clinical heterogeneity have challenged the research, diagnostics and treatment of the disease. Hyperactive and impulsive behaviour has also been observed in dogs, and they could offer a physiologically relevant model for human ADHD. As a part of our ongoing study to understand the molecular etiology of canine anxiety traits, this study was aimed to pilot an approach to identify metabolic biomarkers in canine ADHD-like behaviours for research, diagnostics and treatment purposes.

Methods: We collected fresh plasma samples from 22 German Shepherds with varying ADHD-like behaviours. All dogs were on the same controlled diet for 2 weeks prior to sampling. A liquid chromatography combined with mass spectrometry (LC-MS)-based non-targeted metabolite profiling was performed to identify plasma metabolites correlating with the ADHD-like behaviour of the dogs.

Results: 649 molecular features correlated with ADHD-like behavioural scores (praw < 0.05), and three of them [sn-1 LysoPC(18:3), PC(18:3/18:2) and sn-1 LysoPE(18:2)] had significant correlations also after FDR correction (pFDR < 0.05). Phospholipids were found to negatively correlate with ADHD-like behavioural scores, whereas tryptophan metabolites 3-indolepropionic acid (IPA) and kynurenic acid (KYNA) had negative and positive correlations with ADHD-like behavioural scores, respectively.

Conclusions: Our study identified associations between canine ADHD-like behaviours and metabolites that are involved in lipid and tryptophan metabolisms. The identified metabolites share similarity with earlier findings in human and rodent ADHD models. However, a larger replication study is warranted to validate the discoveries prior to further studies to understand the biological role of the identified metabolites in canine ADHD-like behaviours.

Keywords: ADHD; Dog; Metabolomics; Non-targeted metabolite profiling.

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Figures

Fig. 1
Fig. 1
Correlation plot between metabolites and ADHD-like behavioural scores. Red and blue circles indicate positive and negative correlations, respectively. *praw < 0.05, **praw < 0.01, ***praw < 0.001, #pFDR < 0.05
Fig. 2
Fig. 2
Simplified illustration of the possible metabolic pathways of dietary tryptophan in the intestines. Dietary tryptophan can be degraded in the intestines by enteric bacteria to produce IAA and IPA or KYNA via kynurenine. From the intestines, IPA, IAA and KYNA are transferred to circulation. IPA is known to cross BBB, and thus, can migrate to CNS and act there, but the ability of IAA and KYNA to cross BBB is uncertain. In addition to the degradation of dietary tryptophan in the intestines, KYNA and IAA can also be synthetised from tryptophan in various other tissues in the body, but IPA is solely produced in the intestines by enteric bacteria. BBB blood–brain barrier, CNS central nervous system, IAA indoleacetic acid, IDO indoleamine 2,3-dioxygenase, IPA 3-indolepropionic acid, KYNA kynurenic acid
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References

    1. Biederman J. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatr. 2005;57(11):1215–1220. doi: 10.1016/j.biopsych.2004.10.020. - DOI - PubMed
    1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatr. 2007;164(6):942–948. doi: 10.1176/ajp.2007.164.6.942. - DOI - PubMed
    1. Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatr Clin North Am. 2010;33(1):159–180. doi: 10.1016/j.psc.2009.12.004. - DOI - PMC - PubMed
    1. Tarver J, Daley D, Sayal K. Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts. Child Care Health Dev. 2014;40(6):762–774. doi: 10.1111/cch.12139. - DOI - PubMed
    1. Hoegl T, Heinrich H, Barth W, Losel F, Moll GH, Kratz O. Time course analysis of motor excitability in a response inhibition task according to the level of hyperactivity and impulsivity in children with ADHD. PLoS ONE. 2012;7(9):e46066. doi: 10.1371/journal.pone.0046066. - DOI - PMC - PubMed