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      The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

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          Abstract

          Ghrelin is a peptide hormone released by specialized X/A cells in the stomach and activated by acylation. Following its secretion, it binds to ghrelin receptors in the periphery to regulate energy balance, but it also acts on the central nervous system where it induces a potent orexigenic effect. Several types of stressors have been shown to stimulate ghrelin release in rodents, including nutritional stressors like food deprivation, but also physical and psychological stressors such as foot shocks, social defeat, forced immobilization or chronic unpredictable mild stress. The mechanism through which these stressors drive ghrelin release from the stomach lining remains unknown and, to date, the resulting consequences of ghrelin release for stress coping remain poorly understood. Indeed, ghrelin has been proposed to act as a stress hormone that reduces fear, anxiety- and depression-like behaviors in rodents but some studies suggest that ghrelin may - in contrast - promote such behaviors. In this review, we aim to provide a comprehensive overview of the literature on the role of the ghrelin system in stress coping. We discuss whether ghrelin release is more than a byproduct of disrupted energy homeostasis following stress exposure. Furthermore, we explore the notion that ghrelin receptor signaling in the brain may have effects independent of circulating ghrelin and in what way this might influence stress coping in rodents. Finally, we examine how the ghrelin system could be utilized as a therapeutic avenue in stress-related psychiatric disorders (with a focus on anxiety- and trauma-related disorders), for example to develop novel biomarkers for a better diagnosis or new interventions to tackle relapse or treatment resistance in patients.

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          Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.

          Little is known about lifetime prevalence or age of onset of DSM-IV disorders. To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
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            Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication.

            Little is known about the general population prevalence or severity of DSM-IV mental disorders. To estimate 12-month prevalence, severity, and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders in the recently completed US National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using a fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents 18 years and older. Twelve-month DSM-IV disorders. Twelve-month prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%; substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses. Latent class analysis detected 7 multivariate disorder classes, including 3 highly comorbid classes representing 7% of the population. Although mental disorders are widespread, serious cases are concentrated among a relatively small proportion of cases with high comorbidity.
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              Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States.

              Estimates of 12-month and lifetime prevalence and of lifetime morbid risk (LMR) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) anxiety and mood disorders are presented based on US epidemiological surveys among people aged 13+. The presentation is designed for use in the upcoming DSM-5 manual to provide more coherent estimates than would otherwise be available. Prevalence estimates are presented for the age groups proposed by DSM-5 workgroups as the most useful to consider for policy planning purposes. The LMR/12-month prevalence estimates ranked by frequency are as follows: major depressive episode: 29.9%/8.6%; specific phobia: 18.4/12.1%; social phobia: 13.0/7.4%; post-traumatic stress disorder: 10.1/3.7%; generalized anxiety disorder: 9.0/2.0%; separation anxiety disorder: 8.7/1.2%; panic disorder: 6.8%/2.4%; bipolar disorder: 4.1/1.8%; agoraphobia: 3.7/1.7%; obsessive-compulsive disorder: 2.7/1.2. Four broad patterns of results are most noteworthy: first, that the most common (lifetime prevalence/morbid risk) lifetime anxiety-mood disorders in the United States are major depression (16.6/29.9%), specific phobia (15.6/18.4%), and social phobia (10.7/13.0%) and the least common are agoraphobia (2.5/3.7%) and obsessive-compulsive disorder (2.3/2.7%); second, that the anxiety-mood disorders with the earlier median ages-of-onset are phobias and separation anxiety disorder (ages 15-17) and those with the latest are panic disorder, major depression, and generalized anxiety disorder (ages 23-30); third, that LMR is considerably higher than lifetime prevalence for most anxiety-mood disorders, although the magnitude of this difference is much higher for disorders with later than earlier ages-of-onset; and fourth, that the ratio of 12-month to lifetime prevalence, roughly characterizing persistence, varies meaningfully in ways consistent with independent evidence about differential persistence of these disorders. Copyright © 2012 John Wiley & Sons, Ltd.
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                Author and article information

                Contributors
                Journal
                Front Synaptic Neurosci
                Front Synaptic Neurosci
                Front. Synaptic Neurosci.
                Frontiers in Synaptic Neuroscience
                Frontiers Media S.A.
                1663-3563
                27 October 2020
                2020
                : 12
                : 594484
                Affiliations
                [1] 1Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, University of Innsbruck , Innsbruck, Austria
                [2] 2Department of Pharmaceutical Sciences, Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel , Brussels, Belgium
                Author notes

                Edited by: Sigismund Huck, Medical University of Vienna, Austria

                Reviewed by: Wulf Eckhard Haubensak, Research Institute of Molecular Pathology (IMP), Austria; Harriet Schellekens, University College Cork, Ireland

                *Correspondence: Dimitri De Bundel, dimitri.de.bundel@ 123456vub.be
                Article
                10.3389/fnsyn.2020.594484
                7652849
                33192444
                f973423c-3f82-4c61-bfc6-0657fea65c4a
                Copyright © 2020 Fritz, Singewald and De Bundel.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 August 2020
                : 14 September 2020
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 247, Pages: 23, Words: 0
                Categories
                Neuroscience
                Review

                Neurosciences
                ghrelin,ghsr,stress,anxiety disorders,ptsd,central ghrelin resistance,food intake
                Neurosciences
                ghrelin, ghsr, stress, anxiety disorders, ptsd, central ghrelin resistance, food intake

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