Psychiatric disorders in humans and their counterparts, behavioural disorders in dogs, are the major welfare problems in both species affecting the wellbeing of millions of people and dogs worldwide. Despite extensive research elucidating the pathobiological events leading to the onset of psychiatric/behavioural disorders, the exact etiology remains unattainable. Moreover, the complexity and multicausality of these mental disorders hampers research, addressing the need for more comprehensive approaches to provide insights into the molecular mechanisms of these disorders and to identify disorder-specific biomarkers. The aim of this thesis was to pilot the use of a non-targeted metabolomics approach in canine behavioural research, and to provide novel molecular information concerning two specific behavioural disorders in pet dogs, fearfulness and hyperactivity/impulsivity. Fearfulness is the most common behavioural disorder in dogs, characterized by excessive fear response when confronted with a threatening stimulus. During this thesis work, two separate non-targeted metabolomics characterization studies of canine fearfulness were conducted. The first study aimed to pilot the feasibility and potential of metabolomics technology in canine behavioural research, whereas the second metabolic characterization of canine fear was conducted with a larger sample size to optimize theoretical and analytical limitations observed in the first pilot study. The results showed clear differences in the blood metabolic profiles of fearful and non-fearful control dogs, including increased plasma glutamine abundance in fearful dogs. These alterations potentially originate from the systemic effects of chronic psychological stress. Hyperactive/impulsive dogs manifest inappropriate levels of activity, impulsivity and inattention, corresponding to attention deficit hyperactive disorder (ADHD) in humans. The non-targeted plasma metabolomics showed lower levels of plasma phospholipids in addition to altered tryptophan metabolism in hyperactive and impulsive dogs. These changes may reflect disturbances in the gut microbiota composition in the affected dogs. Collectively, this thesis has demonstrated the feasibility of metabolomics in canine behavioural research and provided novel molecular correlates and potential biomarkers for canine fearfulness and hyperactivity/impulsivity. Additionally, this study identifies changes which also had been reported in other species. This suggests that dogs could be used as a model to aid in gaining better understanding of human psychiatric disorders.
|Myöntöpäivämäärä||14 jouluk. 2018|
|Tila||Julkaistu - 2018|
|OKM-julkaisutyyppi||G5 Tohtorinväitöskirja (artikkeli)|
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