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      Metabolomic Biomarkers in Anxiety Disorders

      review-article
      * , ,
      International Journal of Molecular Sciences
      MDPI
      metabolomics, metabolites, anxiety, biomarkers

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          Abstract

          Anxiety disorders range among the most prevalent psychiatric disorders and belong to the leading disorders in the study of the total global burden of disease. Anxiety disorders are complex conditions, with not fully understood etiological mechanisms. Numerous factors, including psychological, genetic, biological, and chemical factors, are thought to be involved in their etiology. Although the diagnosis of anxiety disorders is constantly evolving, diagnostic manuals rely on symptom lists, not on objective biomarkers and treatment effects are small to moderate. The underlying biological factors that drive anxiety disorders may be better suited to serve as biomarkers for guiding personalized medicine, as they are objective and can be measured externally. Therefore, the incorporation of novel biomarkers into current clinical methods might help to generate a classification system for anxiety disorders that can be linked to the underlying dysfunctional pathways. The study of metabolites (metabolomics) in a large-scale manner shows potential for disease diagnosis, for stratification of patients in a heterogeneous patient population, for monitoring therapeutic efficacy and disease progression, and for defining therapeutic targets. All of these are important properties for anxiety disorders, which is a multifactorial condition not involving a single-gene mutation. This review summarizes recent investigations on metabolomics studies in anxiety disorders.

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          Most cited references116

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          Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression

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            Response rates for CBT for anxiety disorders: Need for standardized criteria

            Full appreciation of the effectiveness of cognitive behavioral therapy (CBT) requires both effect size data and individual rates of positive response. Response rates are particularly helpful for clinicians when choosing among treatment options. However, systematic reviews on cross-study response rates have not been conducted, possibly due to the absence of a standardized metric for calculating response rates. We conducted a systematic review of the treatment outcome literature to determine overall response rates to CBT for anxiety disorders and whether current methods of defining treatment response influence overall response rates. Our database search (2000-2014) resulted in 87 studies that reported response rates and included at least one CBT condition. Results showed that overall treatment response rates across anxiety disorders averaged 49.5% at post-treatment and 53.6% at follow-up. Response rates varied significantly as a function of the properties used to define them. Measures that incorporated more than one criterion, the combination of a reliable change index with a clinical cutoff (a clinically significant change), and intent-to-treat samples yielded lower response rates at post-treatment. Blinded independent assessors yielded higher response rates than unblinded assessors. Based on previous empirical and theoretical work, we recommend that future studies use a clinically significant change index, in an intent-to-treat analysis (using a mixed-model approach), reflecting multiple modalities, and assessed by independent blinded assessors. Our results indicate that such measures are likely to reduce response rates, but may result in a less biased and more accurate representation of improvement and achievement of normative functioning.
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              What does plasma CRP tell us about peripheral and central inflammation in depression?

              Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symptoms of anhedonia. Nevertheless, the relationship between peripheral CRP and other peripheral and central markers of inflammation in depressed patients has not been established. Plasma (n=89) and CSF (n=73) was collected from medically-stable, currently-unmedicated adult outpatients with MDD. Associations among plasma and CSF CRP and plasma and CSF inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF] and IL-1beta) and their soluble receptors/antagonists were examined. Relationships between plasma and CSF inflammatory markers and depressive symptoms including anhedonia and reduced motivation (RM) were also explored. Plasma CRP was correlated with multiple plasma inflammatory markers (all p 3mg/L) and correlated with depressive symptom severity. These findings were driven by CSF TNF, which correlated with RM (r=0.236, p=0.045), and CSF IL-6 soluble receptor, which correlated with anhedonia (r=0.301, p=0.010) in the sample as a whole and particularly females. CRP appears to be a peripheral biomarker that reflects peripheral and central inflammation and seems well-suited for guiding immunotherapies targeting TNF and IL-6 in patients with MDD.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 July 2020
                July 2020
                : 21
                : 13
                : 4784
                Affiliations
                Department for Psychotherapy and Biopsychosocial Health, Danube University Krems, 3500 Krems, Austria; christoph.pieh@ 123456donau-uni.ac.at (C.P.); thomas.probst@ 123456donau-uni.ac.at (T.P.)
                Author notes
                [* ]Correspondence: elke.humer@ 123456donau-uni.ac.at ; Tel.: +43-2732-893-2676
                Author information
                https://orcid.org/0000-0001-9776-0353
                https://orcid.org/0000-0003-2708-303X
                https://orcid.org/0000-0002-6113-2133
                Article
                ijms-21-04784
                10.3390/ijms21134784
                7369790
                32640734
                06420294-db1b-4843-96a2-39f00c3da251
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 June 2020
                : 05 July 2020
                Categories
                Review

                Molecular biology
                metabolomics,metabolites,anxiety,biomarkers
                Molecular biology
                metabolomics, metabolites, anxiety, biomarkers

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