Abstract
BackgroundAnxieties, such as shyness, noise phobia and separation anxiety, are common but poorly understood behavioural problems in domestic dogs, Canis familiaris. Although studies have demonstrated genetic and environmental contributions to anxiety pathogenesis, better understanding of the molecular underpinnings is needed to improve diagnostics, management and treatment plans. As a part of our ongoing canine anxiety genetics efforts, this study aimed to pilot a metabolomics approach in fearful and non-fearful dogs to identify candidate biomarkers for more objective phenotyping purposes and to refer to potential underlying biological problem.MethodsWe collected whole blood samples from 10 fearful and 10 non-fearful Great Danes and performed a liquid chromatography combined with mass spectrometry (LC–MS)-based non-targeted metabolite profiling.ResultsNon-targeted metabolomics analysis detected six 932 metabolite entities in four analytical modes [RP and HILIC; ESI(−) and ESI(+)], of which 239 differed statistically between the test groups. We identified changes in 13 metabolites (fold change ranging from 1.28 to 2.85) between fearful and non-fearful dogs, including hypoxanthine, indoxylsulfate and several phospholipids. These molecules are involved in oxidative stress, tryptophan and lipid metabolisms.ConclusionsWe identified significant alterations in the metabolism of fearful dogs, and some of these changes appear relevant to anxiety also in other species. This pilot study demonstrates the feasibility of the non-targeted metabolomics and warrants a larger replication study to confirm the role of the identified biomarkers and pathways in canine anxiety.
Highlights
Anxieties, such as shyness, noise phobia and separation anxiety, are common but poorly understood behavioural problems in domestic dogs, Canis familiaris
Our results reveal changes in several anxiety-relevant components in fearful dogs and warrant a larger metabolomics study in canine anxiety to replicate the findings in this pilot study
We detected a total of 6 932 molecular features in the four separate liquid chromatography (LC)–mass spectrometry (MS) runs, of which 239 were differential between the two groups (Student’s t-test, p value < 0.05; fold change (FC) ≥±1.2; partial least-squares discriminant analysis (PLS-DA) variable importance projection (VIP) >1)
Summary
Anxieties, such as shyness, noise phobia and separation anxiety, are common but poorly understood behavioural problems in domestic dogs, Canis familiaris. As a part of our ongoing canine anxiety genetics efforts, this study aimed to pilot a metabolomics approach in fearful and non-fearful dogs to identify candidate biomarkers for more objective phenotyping purposes and to refer to potential underlying biological problem. Anxiety-related disorders, including compulsions, fearfulness, noise phobia, generalized anxiety and separation anxiety, are common but complex and poorly understood behavioural problems in domestic dogs (Canis familiaris) [1,2,3]. Ethological and pharmacological studies suggest that the underlying biochemical mechanisms are shared in dogs and humans This is demonstrated, for example, by a successful treatment of the dogs with. Metabolic profiling of schizophrenia has revealed changes in glutamine and arginine metabolism, which may reflect genetic susceptibility to this neuropsychiatric disorder [18]
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