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LOQ for amino acids was largely under plasmatic concentration levels 0. LOQ established for TAs and catecholamines was sufficient to perform the quantification in plasma samples 0. The concentration of OCT and SYN resulted to be lower than the LOQ for most of the collected sample and, then, their concentration should be considered as semi-quantitative. Our study was a pilot cross-sectional study.

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No a priori information was available to perform a power analysis. In this respect, data analysis should be interpreted as exploratory. Again, model validation was performed by internal validation procedures as described in the following. Statistical data analysis aimed to characterize the groups of subjects under investigation was performed by univariate and multivariate data analysis.

As the first step of data analysis, Principal Component Analysis PCA was applied to every single group to highlight the presence of outliers whereas the effects of age, sex, and group on the concentration of the measured metabolites were investigated by Multiple Linear Regression MLR with Box-Cox transformation.


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PCA is a multivariate unsupervised technique that produces new data representations where the so-called principal components, obtained linearly combining the measured variables, are used to summarize the information contained in the data Trends in the data, clusters of observations and outliers can be detected exploring the latent space and the residuals of the PCA model. On the other hand, MLR is a multivariate regression technique that allows the investigation of the relationships between factors age, sex, and group and response metabolite concentration taking into account the effect of all the factors at the same time.

The Box-Cox transformation has been applied to have normally distributed residuals in order to perform an accurate statistical inference. MLR cannot be applied in the case of strongly correlated factors because the variance of the regression coefficients becomes very large making it difficult to obtain precise estimates of the separate effects of the factors, and large errors in prediction are obtained. Thus, we compared the three groups together. PLS-DA is a multivariate classification technique that is usually applied when the factors i. The measured variables are linearly combined to obtain a new set of variables, called latent variables, which are able to discriminate the observations.

N-fold cross-validation CV is applied to estimate the power in prediction of the PLS-DA model and determine the number of latent variables to be calculated. The parameter Q 2 CV N-fold , that has the same form of the goodness-of-fit R 2 but uses the predicted responses during CV instead of the calculated responses, is used to describe the performance of the model.

Finally, we considered the de novo group as a control group and performed pair comparisons with the healthy group and the group of treated patients in order to discover putative markers for the disease and for its progression, respectively. Receiver Operating Characteristic ROC analysis and PLS-DA with stability selection based on Monte-Carlo sampling 39 were applied to investigate the differences between the groups under investigation and discover putative markers. The central idea of stability selection is that real data variations should be present consistently, and therefore should be found even under perturbation of the data by sub-sampling.

During stability selection, random subsamples of the collected samples were extracted by Monte-Carlo sampling with a prior probability of 0. Specifically, all the variables showing VIP under a given threshold are excluded during model building. The threshold to use has been defined on the basis of the best Q 2 CV 7-fold.

The predictive performance of each model was estimated by means of ROC analysis of the outcomes of the predictions of which samples would be excluded during sub-sampling. Within the set of PLS-DA VIP-based models obtained by stability selection, the most frequently selected variables were identified as relevant variables. Braak, E. Acta neuropathologica , — Braak, H. Niwa, F.

Berg, D. Mehta, S. Ibanez, C. Recent advances and applications of metabolomics to investigate neurodegenerative diseases. Havelund, J.


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  7. Gainetdinov, R. Trace Amines and Their Receptors. Miller, G. The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. Sotnikova, T. Trace amine associated receptor 1 and movement control.

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    Geracitano, R. Inhibitory effects of trace amines on rat midbrain dopaminergic neurons. Berry, M. Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. Zucchi, R. Trace amine-associated receptors and their ligands. Burchett, S. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Perry, M. Review of recent advances in analytical techniques for the determination of neurotransmitters. HPLC electrochemical detection of trace amines in human plasma and platelets and expression of mRNA transcripts of trace amine receptors in circulating leukocytes.

    Neuroscience letters , 89—92 Tryptamine levels are low in plasma of chronic migraine and chronic tension-type headache. Chen, J. Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Dunand, M. High-throughput and sensitive quantitation of plasma catecholamines by ultraperformance liquid chromatography-tandem mass spectrometry using a solid phase microwell extraction plate. Trabado, S. The human plasma-metabolome: Reference values in French healthy volunteers; impact of cholesterol, gender and age. PLoS One 12 , e Zhou, G.

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    Benztropine analogs as therapeutic agents in cocaine addiction: Neurochemical and pharmacokinetic-dynamic studies in animal models of relapse , Spanish Ministry of Education and Science, Plan Nacional, Personal tools Web Editor Log in. Search Site only in current section. Advanced Search…. Search Site.

    Juan J. Journal Articles Hamilton J, Lee JA, Canales JJ Chronic unilateral stimulation of the nucleus accumbens at high or low frequencies attenuates relapse to cocaine seeking in an animal model. Journal Articles Pei, Y. Journal Articles Ferragud, A. European Journal of Pharmacology Journal Articles Canales, J. Developmental Neuroscience 36 1 : Addiction Biology 18 4 : Progress in Neuro-Psychopharmacology and Biological Psychiatry New York: Nova Science Publishers. Edited Books Capilla-Gonzalez, V. PLoS One 7 1 : e Journal Articles Revel, F.

    Gene Music using Protein Sequence of TAAR1 "TRACE AMINE ASSOCIATED RECEPTOR 1"

    Biological Psychiatry 72 11 : Journal Articles Lin, Z. Save to Library. Create Alert. Share This Paper. Tables and Topics from this paper.

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    Citations Publications citing this paper. The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Mark D. Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.