Double-Blind, Controlled, Crossover Trial of Inositol Versus Fluvoxamine for the Treatment of Panic Disorder

Palatnik, Alex; K, Frolov; Fux, Mendel; Benjamin, Jonathan

doi:10.1097/00004714-200106000-00014

Cited by 85 publications

(38 citation statements)

References 22 publications

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“…3). Myo-inositol has been shown to have antidepressant and anxiolytic activities in both humans and animals (23)(24)(25)(26)(27)(28). Also of interest is the finding that several energy metabolism related metabolites, including amino acids, cholesterol, fumarate, and malate, were found at different levels between the two lines.…”

Section: Resultsmentioning

confidence: 99%

Proteomic and Metabolomic Profiling of a Trait Anxiety Mouse Model Implicate Affected Pathways

Zhang

Filiou

Reckow

et al. 2011

Molecular & Cellular Proteomics

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Depression and anxiety disorders affect a great number of people worldwide. Whereas singular factors have been associated with the pathogenesis of psychiatric disorders, growing evidence emphasizes the significance of dysfunctional neural circuits and signaling pathways. Hence, a systems biology approach is required to get a better understanding of psychiatric phenotypes such as depression and anxiety. Furthermore, the availability of biomarkers for these disorders is critical for improved diagnosis and monitoring treatment response. In the present study, a mouse model presenting with robust high versus low anxiety phenotypes was subjected to thorough molecular biomarker and pathway discovery analyses. Reference animals were metabolically labeled with the stable 15 N isotope allowing an accurate comparison of protein expression levels between the high anxiety-related behavior versus low anxiety-related behavior mouse lines using quantitative mass spectrometry. Plasma metabolomic analyses identified a number of small molecule biomarkers characteristic for the anxiety phenotype with particular focus on myo-inositol and glutamate as well as the intermediates involved in the tricarboxylic acid cycle. In silico analyses suggested pathways and subnetworks as relevant for the anxiety phenotype. Our data demonstrate that the high anxietyrelated behavior and low anxiety-related behavior mouse model is a valuable tool for anxiety disorder drug discovery efforts. Molecular & Cellular Proteomics 10: 10.1074/mcp.M111.008110, 1-11, 2011.For an improved understanding of the etiology of complex diseases such as psychiatric disorders the elucidation of molecular pathways is critical. In this regard biomarker information can deliver valuable data not only on individual molecular entities but at the same time on pathways critical for disease pathobiology, thus yielding important information for the development of therapeutic agents.Animal models have the capability to mimic certain aspects of complex disorders and thereby untangle complicated phenotypes such as anxiety, which can be measured in the mouse with the help of the elevated plus maze (EPM) 1 and other anxiety tests (1). In earlier studies we have identified proteome differences in a mouse model of extremes in trait anxiety that are qualitative and quantitative in nature. Whereas the enzyme enolase phosphatase was found as a different isoform in high (HAB) versus low (LAB) anxiety-related behavior mice, another enzyme, glyoxalase-1 (Glx1), showed altered expression levels between the two lines (1, 2). Our approach thus considers the two poles of the continuum "anxiety": vulnerability of individuals with high risk scores as well as resilience of individuals with low risk scores at the often neglected "other end" of the continuum of polygenic liability (3).In order to analyze the proteomes of the HAB and LAB mouse lines in greater detail, we have used a comprehensive and accurate proteomics platform that involves metabolic labeling of live animals with stable isotopes follo...

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Section: Resultsmentioning

confidence: 99%

Proteomic and Metabolomic Profiling of a Trait Anxiety Mouse Model Implicate Affected Pathways

Zhang

Filiou

Reckow

et al. 2011

Molecular & Cellular Proteomics

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“…Moreover, its therapeutic use has been extensively studied in autism, and other psychiatric disorders, in polycystic ovary syndrome, in patients on lithium therapy, and in respiratory distress syndrome (Benjamin et al, 1995;Colodny and Hoffman, 1998;Levine et al, 1997;Nestler et al, 1999;Howlett and Ohlsson, 2003). No significant side effects of inositol therapy have been reported in any of the previous studies, even at high doses (up to 18 g/day in psychiatric patients) (Palatnik et al, 2001).…”

Section: To the Editormentioning

confidence: 98%

Inositol supplementation in pregnancies at risk of apparently folate‐resistant NTDs

Cavalli

Tedoldi

Riboli

2008

Birth Defects Research

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“…(256) ); mental health (966,967) ; osmotic demyelination syndrome (968) ; volume regulation during persistent osmotic stress (969) ; cancer (686) ; diabetic polyneuropathy and nerve conduction (970) ; intestinal lipodystrophy (963) Policosanol: Octacosanol in human health (302) ; CVD (304) ; lipid, cholesterol and LDL (303,306,971 -973) ; cholesterol biosynthesis and LDL catabolism (973) ; hydroxymethylglutaryl-coenzyme A (HMGCoA) reductase (974) ; LDL peroxidation (307) ; membrane lipid peroxidation (975) ; lipid metabolism (301) ; platelet aggregation and thromboxane generation, endothelial damage and foam cell formation (976,977) ; cytoprotection in gastric ulcer (978) ; athletic performances (979) ; cardiac events, and cholesterol and anti-aggregatory effects (cited in Taylor et al (302) ); smooth muscle cell proliferation (980) ; anti-fatigue drug (302) Melatonin (981) : Mood, happiness, sleep and brain neuromodulation in Alzheimer's disease (309,310) ; antioxidant (982,983) ; corticoid receptor (984) ; scavenger of hydroxyl radicals (985) ; brain GSH peroxidase activity (986) ; gene expression for antioxidant enzyme (987) ; sleep -wake regulation (309,988) ; DNA damage (989) ; lifespan (990) ; oncostatic role and antiproliferative effect (311,312) ; cancers (991) para-Aminobenzoic acid (PABA): Acetylation in blood and other tissues (315,…”

Section: Appendixmentioning

confidence: 99%

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

2010

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Epidemiological studies have clearly shown that whole-grain cereals can protect against obesity, diabetes, CVD and cancers. The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are today well-recognised mechanisms in this protection. Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as a-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the 'whole-grain package', and the most promising ways for improving the nutritional quality of cereal products are discussed. Whole-grain wheat: Bioactive compounds: Physiological mechanisms: Health IntroductionThere is growing evidence that whole-grain cereal products protect against the development of chronic diseases. The most important of these in terms of public health are obesity (1,2) , the metabolic syndrome (3,4) , type 2 diabetes (5,6) , CVD (7) and cancers (8 -12) . Whole-grain cereal consumption has also been shown to be protective against mortality, as was shown with inflammation-related death (i.e. noncardiovascular and non-cancer inflammatory diseases such as, for example, respiratory system diseases) (13) and with cancer and CVD (4,14,15) . These conclusions are supported by the effects of consuming refined cereal products (bread, pasta and rice), as these have been associated with an increased risk of digestive tract, pharynx, larynx and thyroid cancers in northern Italians (16) . However, an association between a lower risk of developing a chronic disease and a high whole-grain cereal consumption does not mean a direct causal relationship and provides no information about the physiological mechanisms involved.These metabolic diseases are related to our daily lifestyle, no...

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Double-Blind, Controlled, Crossover Trial of Inositol Versus Fluvoxamine for the Treatment of Panic Disorder

Cited by 85 publications

References 22 publications

Proteomic and Metabolomic Profiling of a Trait Anxiety Mouse Model Implicate Affected Pathways

Proteomic and Metabolomic Profiling of a Trait Anxiety Mouse Model Implicate Affected Pathways

Inositol supplementation in pregnancies at risk of apparently folate‐resistant NTDs

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

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