The Folkhalsan Research Center

Helsinki, Finland

The Folkhalsan Research Center

Helsinki, Finland
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Puurunen J.,University of Eastern Finland | Tiira K.,University of Helsinki | Tiira K.,The Folkhalsan Research Center | Lehtonen M.,University of Eastern Finland | And 5 more authors.
Behavioral and Brain Functions | Year: 2016

Background: Anxieties, 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. Methods: We 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. Results: Non-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. Conclusions: We 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. © 2016 Puurunen et al.


Puurunen J.,University of Helsinki | Puurunen J.,The Folkhalsan Research Center | Sulkama S.,University of Helsinki | Sulkama S.,The Folkhalsan Research Center | And 9 more authors.
Behavioral and Brain Functions | Year: 2016

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. © 2016 The Author(s).


Tiira K.,University of Helsinki | Tiira K.,The Folkhalsan Research Center | Hakosalo O.,University of Helsinki | Hakosalo O.,The Folkhalsan Research Center | And 8 more authors.
PLoS ONE | Year: 2012

Obsessive Compulsive Disorder (OCD) is a neuropsychiatric disorder observed both in humans and animals. Examples of Canine Compulsive Disorder (CD) include excessive tail chasing (TC), light/shadow chasing and flank sucking. We performed a questionnaire survey to investigate the characteristics of compulsive (TC) and its possible associations with environmental correlates and personality in a pet population of 368 dogs from four dog breeds. We observed an early onset of TC at 3-6 months of age and a large variation in TC frequency in all breeds, with an overrepresentation of milder cases. Almost half of the TC dogs showed lowered responsiveness during bouts and displayed also other types of compulsions more often than the controls. Interestingly, dogs that received dietary supplements, especially vitamins and minerals, expressed less TC compared to dogs that did not receive any supplements. Neutered females had less TC, suggesting an influence of ovarian hormones on TC. Tail chasers were shyer and had separated earlier from their mothers than the controls. Finally, our genetic study did not find an association between TC and CDH2, a locus previously associated with the canine flank sucking compulsion. In conclusion, the early-onset and the variable nature of the repetitive behaviour, which is affected by environmental factors such as micronutrients, neutering and maternal care, share several similar components between canine and human compulsions and supports canine TC as a model for human OCD. © 2012 Tiira et al.


Tiira K.,University of Helsinki | Tiira K.,The Folkhalsan Research Center | Lohi H.,University of Helsinki | Lohi H.,The Folkhalsan Research Center
Applied Animal Behaviour Science | Year: 2014

Canine behavior can be assessed through behavioral testing or questionnaire surveys. Behavioral tests, often observed by independent experts, can provide objective data, but capture only a short behavioral sequence in a defined situation and are practical only for small study cohorts. Questionnaires can be targeted to much larger populations and provide long-term perspectives on behaviors, including potential correlated environmental factors. However, questionnaires are sensitive for misinterpretations and the subjectivity of the participant may affect the outcome. Therefore, particular attention has to be paid to structure and form of the questions to ensure that the questionnaire measures what it is supposed to measure. We have initiated a program on genetic studies in canine anxiety and have developed a questionnaire for behavioral phenotyping. The aim of the questionnaire is to identify the most fearful dogs (cases) and dogs not showing fear (controls) within and across breeds for gene mapping purposes. Knowing the challenges in the phenotyping of complex neurobehavioral traits, the aim of this study was to assess the external and convergent validity and re-test reliability of the developed questionnaire. External validity was assessed by comparing questionnaire data against short behavioral test of selected dogs (N=54), and convergent validity was estimated using "known group comparisons", i.e. whether the dogs with separation anxiety have also more noise phobia. Re-test reliability was evaluated from the subsample (N=36) of the owners who filled the questionnaire twice within an 8-month period. We found an excellent correlation between questionnaire data and the behavioral test, and the most important questions on the fearful reactions toward strangers, had the highest correlation with the behavioral test in which the dog met a stranger (mean rs=0.63). Convergent validity was also well demonstrated by showing that a known co-morbid anxiety trait, separation anxiety, was more common in noise sensitive dogs as expected (Wilcoxon rank-sum test χ2 1,1732=9.8, p<0.01). Similarly, the test-retest reliability was good (mean values: 0.69 Spearman correlation; 0.59 Kappa value). Most importantly, the questions asking the frequency of fear reactions had excellent repeatability (mean frequency of fear reactions toward humans, dogs and situations 0.78 Spearman correlation, toward thunder, gunshot, fireworks, 0.76 Spearman correlation). These results encourage a conclusion that our questionnaire may serve as a reliable phenotyping tool for fearfulness in dogs, which, in turn, should help us to establish sufficiently large study cohorts for successful genetic analyses. © 2014 Elsevier B.V.

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