A non-targeted metabolite profiling pilot study suggests that tryptophan and lipid metabolisms are linked with ADHD-like behaviours in dogs.
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.
Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, Biomedicum Helsinki, P.O.Box 63, 00014, Helsinki, Finland.|The Folkhälsan Research Center, Helsinki, Finland.
Jenni
J
Puurunen
Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, Biomedicum Helsinki, P.O.Box 63, 00014, Helsinki, Finland.|The Folkhälsan Research Center, Helsinki, Finland.
Sini
S
Sulkama
Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, Biomedicum Helsinki, P.O.Box 63, 00014, Helsinki, Finland.|The Folkhälsan Research Center, Helsinki, Finland.
Katriina
K
Tiira
Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, Biomedicum Helsinki, P.O.Box 63, 00014, Helsinki, Finland.|The Folkhälsan Research Center, Helsinki, Finland.
Cesar
C
Araujo
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Marko
M
Lehtonen
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.|LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland.
Kati
K
Hanhineva
Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, Biomedicum Helsinki, P.O.Box 63, 00014, Helsinki, Finland. hannes.lohi@helsinki.fi.|The Folkhälsan Research Center, Helsinki, Finland. hannes.lohi@helsinki.fi.
Hannes
H
Lohi
ADHD; Dog; Metabolomics; Non-targeted metabolite profiling
Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):299-308
16962757
J Affect Disord. 2007 Feb;98(1-2):143-51
16952400
Amino Acids. 2008 Aug;35(2):503-5
18235993
Annu Rev Plant Biol. 2010;61:49-64
20192736
Anal Chim Acta. 2012 Jan 20;711:7-16
22152789
Anim Genet. 2007 Dec;38(6):629-33
17986156
J Neurosci Res. 2009 Jul;87(9):2126-37
19235887
Rapid Commun Mass Spectrom. 2009 Jul;23(14):2125-38
19517478
Psychiatry Res. 2014 Sep 30;219(1):10-24
24863865
J Cell Biochem. 2001;81(3):507-13
11255233
Mol Nutr Food Res. 2013 Mar;57(3):523-35
23349065
FASEB J. 2015 Jun;29(6):2207-22
25713056
PLoS One. 2012;7(9):e46066
23049936
Genome Med. 2016 Apr 21;8(1):46
27102537
Clin Ther. 2015 May 1;37(5):984-95
26046241
Prostaglandins Leukot Essent Fatty Acids. 2000 Jul-Aug;63(1-2):79-87
10970718
J Neural Transm (Vienna). 2012 Feb;119(2):133-9
22215208
Behav Brain Funct. 2015 Nov 05;11(1):36
26542774
Neuropsychopharmacology. 2009 Jan;34(1):173-86
18843269
Behav Brain Funct. 2016 Feb 12;12 (1):7
26867941
Behav Brain Funct. 2010 Jan 04;6:1
20047681
Neurosci Lett. 1998 Jan 16;240(3):177-81
9502233
J Psychiatr Res. 2012 Apr;46(4):451-5
22257388
Life Sci. 1995;57(21):1935-47
7475943
Neuropsychopharmacology. 2012 Mar;37(4):939-49
22071871
Biochim Biophys Acta. 2015 Aug;1851(8):1052-65
25542508
Schizophr Bull. 2011 Nov;37(6):1147-56
21036897
Am J Clin Nutr. 1987 Feb;45(2):443-55
3812343
Nat Rev Microbiol. 2012 Nov;10(11):735-42
23000955
Psychoneuroendocrinology. 2015 Feb;52:200-11
25486577
Physiol Behav. 2012 Feb 1;105(3):676-82
21986321
J Child Psychol Psychiatry. 1996 Feb;37(2):225-7
8682903
Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):259-69
16963244
PLoS One. 2013 Dec 23;8(12):e82948
24376613
Psychiatr Clin North Am. 2010 Mar;33(1):159-80
20159345
Psychiatry Investig. 2015 Jul;12(3):361-6
26207130
Am J Clin Nutr. 1995 Oct;62(4):761-8
7572706
Lipids. 2004 Feb;39(2):117-23
15134138
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:304-13
24184687
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3698-703
19234110
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1491-4
20732373
Rapid Commun Mass Spectrom. 2009 Oct;23(19):3243-54
19725045
Biol Psychiatry. 2005 Jun 1;57(11):1215-20
15949990
Child Care Health Dev. 2014 Nov;40(6):762-74
24725022
Lipids. 2000 Dec;35(12):1305-12
11201991
Neurochem Int. 2015 Mar;82:52-68
25684070
J Nutr. 1994 Dec;124(12):2466-76
16856329
J Am Soc Mass Spectrom. 2002 May;13(5):558-70
12019979
Pediatr Allergy Immunol. 2014 May;25(3):218-26
24236934
J Biol Chem. 1959 Jan;234(1):81-6
13610897
Am J Psychiatry. 2007 Jun;164(6):942-8
17541055
Mass Spectrom Rev. 2011 Jul-Aug;30(4):579-99
21656842
Psychiatry Clin Neurosci. 2012 Apr;66(3):220-6
22443244
PLoS One. 2013 Apr 22;8(4):e59749
23630570
Schizophr Bull. 2010 Mar;36(2):211-8
20147364
Clin Psychol Rev. 2014 Aug;34(6):496-505
25181335
J Nutr Biochem. 2004 Aug;15(8):467-72
15302081
J Appl Microbiol. 2006 Jun;100(6):1261-71
16696673
Neurosci Lett. 2000 Apr 21;284(1-2):25-8
10771153
Prostaglandins Leukot Essent Fatty Acids. 2014 Jul-Aug;91(1-2):49-60
24958525
Mol Biosyst. 2012 Feb;8(2):470-81
22041788
Prostaglandins Leukot Essent Fatty Acids. 2008 Jul-Aug;79(1-2):47-53
18757191