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      Modulation of SF1 Neuron Activity Coordinately Regulates Both Feeding Behavior and Associated Emotional States

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          Summary

          Feeding requires the integration of homeostatic drives with emotional states relevant to food procurement in potentially hostile environments. The ventromedial hypothalamus (VMH) regulates feeding and anxiety, but how these are controlled in a concerted manner remains unclear. Using pharmacogenetic, optogenetic, and calcium imaging approaches with a battery of behavioral assays, we demonstrate that VMH steroidogenic factor 1 (SF1) neurons constitute a nutritionally sensitive switch, modulating the competing motivations of feeding and avoidance of potentially dangerous environments. Acute alteration of SF1 neuronal activity alters food intake via changes in appetite and feeding-related behaviors, including locomotion, exploration, anxiety, and valence. In turn, intrinsic SF1 neuron activity is low during feeding and increases with both feeding termination and stress. Our findings identify SF1 neurons as a key part of the neurocircuitry that controls both feeding and related affective states, giving potential insights into the relationship between disordered eating and stress-associated psychological disorders in humans.

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          Highlights

          • Intrinsic SF1 neuron activity is low during feeding and increases when feeding stops

          • Manipulating SF1 neuron activity controls food intake and related behaviors

          • Response to SF1 neuron activity is sensitive to energy status

          • SF1 neural circuitry integrates feeding and emotional states

          Abstract

          Viskaitis et al. show that hypothalamic SF1 neurons act as a nutrient-sensitive switch between feeding and anxiety states. They identify a key circuit that permits feeding and related behaviors when its activity is low but primes the animal to stop feeding and to face potential stresses when activity is high.

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          The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

          To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.
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            The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis.

            Anxiety disorders are the most prevalent mental disorders in developed countries. Obesity is hypothesized to be a risk factor for anxiety disorders but evidence supporting an association between these two conditions is not clear. The objectives of this paper were to systematically review the literature for a link between obesity and anxiety disorders in the general population, and to present a pooled estimate of association. We performed a systematic search for epidemiological articles reporting on obesity (explanatory variable) and anxiety disorders (outcome variable) in seven bibliographical databases. Two independent reviewers abstracted the data and assessed study quality. We found 16 studies (2 prospective and 14 cross-sectional) that met the selection criteria. Measures of effect from prospective data were mixed but cross-sectional evidence suggested a positive association between obesity and anxiety. The pooled odds ratio from cross-sectional studies was 1.4 (confidence interval: 1.2-1.6). Subgroup analyses revealed a positive association in men and women. Overall, a moderate level of evidence exists for a positive association between obesity and anxiety disorders. Questions remain regarding the role of obesity severity and subtypes of anxiety disorders. The causal relationship from obesity to anxiety disorders could not be inferred from current data; future etiologic studies are recommended.
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              Depression and obesity.

              The prevalence of depression (10%) and overweight (65%) indicates that there is a probability that they will co-occur, but are they functionally related? This report used the moderator/mediator distinction to approach this question. Moderators, such as severity of depression, severity of obesity, gender, socioeconomic status (SES), gene-by-environment interactions and childhood experiences, specify for whom and under what conditions effects of agents occur. Mediators, such as eating and physical activity, teasing, disordered eating and stress, identify why and how they exert these effects. Major depression among adolescents predicted a greater body mass index (BMI = kg/m(2)) in adult life than for persons who had not been depressed. Among women, obesity is related to major depression, and this relationship increases among those of high SES, while among men, there is an inverse relationship between depression and obesity, and there is no relationship with SES. A genetic susceptibility to both depression and obesity may be expressed by environmental influences. Adverse childhood experiences promote the development of both depression and obesity, and, presumably, their co-occurrence. As most knowledge about the relationship between these two factors results from research devoted to other topics, a systematic exploration of this relationship would help to elucidate causal mechanisms and opportunities for prevention and treatment.
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                Author and article information

                Contributors
                Journal
                Cell Rep
                Cell Rep
                Cell Reports
                Cell Press
                2211-1247
                19 December 2017
                19 December 2017
                19 December 2017
                : 21
                : 12
                : 3559-3572
                Affiliations
                [1 ]MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK
                [2 ]Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK
                [3 ]Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
                Author notes
                []Corresponding author d.withers@ 123456imperial.ac.uk
                [4]

                Lead Contact

                Article
                S2211-1247(17)31756-4
                10.1016/j.celrep.2017.11.089
                5746599
                29262334
                d65a88f0-e301-434b-a5f5-03dcbdaf7bdd
                © 2017 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 July 2017
                : 18 October 2017
                : 27 November 2017
                Categories
                Article

                Cell biology
                ventromedial hypothalamus,steroidogenic factor 1,feeding,affective state,stress response,optogenetics,chemogenetics

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