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.

中文翻译：

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一项非目标代谢物分析的初步研究表明，色氨酸和脂质代谢与狗中多动症样行为有关。

背景技术注意力缺陷多动障碍（ADHD）是全世界人群中普遍存在的多因素神经精神病。复杂的病因和临床异质性已经对该疾病的研究，诊断和治疗提出了挑战。在狗中也观察到过动和冲动行为，它们可以为人多动症提供生理相关的模型。作为我们正在进行的旨在了解犬类焦虑性状的分子病因学的研究的一部分，本研究旨在开创一种方法来识别犬类ADHD行为中的代谢生物标志物，以进行研究，诊断和治疗。方法我们从22名德国牧羊犬中收集了新鲜血浆样品，这些样品具有多种类似ADHD的行为。在取样前2周，所有的狗都接受相同的控制饮食。结合基于质谱（LC-MS）的非目标代谢物谱分析进行了液相色谱法，以鉴定与狗多动症样行为相关的血浆代谢物。结果649个分子特征与类似ADHD的行为得分相关（praw <0.05），其中三个[sn-1 LysoPC（18：3），PC（18：3/18：2）和sn-1 LysoPE（18： 2）]在FDR校正后也具有显着相关性（pFDR <0.05）。发现磷脂与ADHD样行为评分呈负相关，而色氨酸代谢产物3-吲哚丙酸（IPA）和尿酸（KYNA）与ADHD样行为评分呈负相关和正相关。结论我们的研究确定了犬多动症样行为与脂类和色氨酸代谢中涉及的代谢物之间的关联。鉴定出的代谢物与人类和啮齿动物ADHD模型的早期发现具有相似性。但是，在进行进一步的研究之前，有必要进行较大规模的复制研究来验证发现，以了解所识别代谢物在犬类ADHD行为中的生物学作用。