Hypothesis: Clues From Mammalian Hibernation for Treating Patients With Anorexia Nervosa.
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ABSTRACT:
SUBMITTER: Scolnick B
PROVIDER: S-EPMC6240652 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Hypothesis: Clues From Mammalian Hibernation for Treating Patients With Anorexia Nervosa.
Frontiers in psychology 20181112
This hypothesis is that anorexia nervosa (AN) is a biologically driven disorder, and mammalian hibernation may offer clues to its pathogenesis. Using this approach, this hypothesis offers suggestions for employing heart rate variability as an early diagnostic test for AN; employing the ketogenic diet for refeeding patients, attending to omega 3:6 ratio of polyunsaturated fatty acids (PUFAs) in the refeeding diet; and exploring clinical trials of the endocannabinoid-like agent, palmitoylethanolam ...[more]
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2023-10-31 | GSE245978 | GEO
Project description:Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients.
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Project description:As part of the Genetic Consortium for Anorexia Nervosa (GCAN) and Wellcome Trust Case
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Project description:ObjectivesRecent neuroimaging studies have indicated that the mesolimbic pathway, known to work as reward neuronal circuitry, regulates cognitive-behavioral flexibility in prolonged anorexia nervosa (AN). Although AN is associated with the highest mortality rate among psychiatric disorders, there have been few neuropathological studies on this topic. This study aims to identify alterations of the reward circuitry regions, especially in the nucleus accumbens (NAcc), using AN brain tissues.MethodsThe neuronal networks in AN cases and controls were examined by immunohistochemistry directed at tyrosine hydroxylase (TH; dopaminergic neuron marker) and glial fibrillary acidic protein (GFAP; astrocyte marker). We also immunochemically analyzed frozen samples presenting astrogliosis, especially in the NAcc and striatum.ResultsHistologically, neuronal deformation with cytoplasmic shrinkage was seen in reward-related brain regions, such as the orbitofrontal cortex/anterior cingulate cortex. The NAcc showed massive GFAP-positive astrocytes and dot-like protrusions of astrocytes in the shell compartment. In the shell, TH and GFAP immunoreactivities revealed prominent astrogliosis within striosomes, which receive projection from the ventral tegmental area (VTA). The numbers of GFAP-positive astrocytes in the NAcc (P = 0.0079) and VTA (P = 0.0025) of AN cases were significantly higher than those of controls. Strongly immunoreactive 18 to 25 kDa bands, which might represent degradation products, were detected only in the NAcc of AN cases. Clinically, all cases presented cognitive rigidity, which might reflect a deficit of the reward pathway.ConclusionOur findings suggest impaired dopaminergic innervation between the NAcc and VTA in AN. Functional dysconnectivity in the reward-related network might induce neuropsychiatric symptoms associated with AN.
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Project description:Anorexia nervosa (AN) is a complex debilitating disease characterized by intense fear of weight gain and excessive exercise. It is the deadliest of any psychiatric disorder with a high rate of recidivism, yet its pathophysiology is unclear. The Activity-Based Anorexia (ABA) paradigm is a widely accepted mouse model of AN that recapitulates hypophagia and hyperactivity despite reduced body weight, however, not the chronicity. Here, we modified the prototypical ABA paradigm to increase the time to lose 25% of baseline body weight from less than 7 days to more than 2 weeks. We used this paradigm to identify persistently altered genes after weight restoration that represent a metabolic memory of under-nutrition and may contribute to AN relapse. We focused on adipose tissue as it was identified as a major location of metabolic memory of over-nutririon. We identified 300 persistently dysregulated genes, including Calm2 and Vps13d, which could be potential global regulators of metabolic memory in both chronic over- and under-nutrition. However, despite being on the opposite spectrum of weight perturbations, the majority of metabolic memory genes of under- and over-nutrition do not overlap, suggestive of the different mechanisms involved in these extreme nutritional statuses.
2023-08-23 | GSE229316 | GEO
Project description:ObjectiveAntidiuretic hormone (ADH) is involved in the response to stress and in depression and anxiety. However, studies on ADH in anorexia nervosa (AN) show conflicting results. A major reason for this may be methodological challenges due to short half-life of ADH in circulation and rapid degradation in vitro. To overcome these obstacles, copeptin, the C-terminal fragment stemming from the ADH precursor, has been increasingly used as a stable clinical measure for ADH. Furthermore, copeptin has been recognized as a biomarker of insulin resistance in obesity.MethodsWe measured fasting copeptin in plasma from 25 normohydrated, stable women with AN (BMI 13.0 ± 2.0) and 25 age-matched women.ResultsNo difference in copeptin levels was found (6.8 ± 1.8 vs. 5.5 ± 0.5 pmol/L). Confirmatory, copeptin concentrations were correlated to insulin resistance assessed by the homeostasis model assessment of insulin resistance.DiscussionWe report for the first time that copeptin level as a marker of ADH activity is not altered in fluid- and electrolyte-stabilized patients with severe AN patients, indicating that ADH may not be crucial in the pathophysiological involvement of psychologic stress in AN.
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Project description:Purpose of reviewGenetic factors contribute to the etiology of anorexia nervosa (AN). This review synthesizes the current state of knowledge about the genetic etiology of AN, provides directions for future research, and discusses clinical implications for this research.Recent findingsCandidate gene meta-analyses indicate serotonin genes may be involved in the genetic etiology of AN. Three genome-wide association studies have been conducted and one genome-wide significant locus was identified. Cross-disorder analyses suggest shared genetic risk between AN and several psychiatric, educational, and medical phenotypes. Much has been learned about the genetic etiology of AN over the past 3 decades. However, to fully understand the genetic architecture, we must consider all aspects including common variation, cross-disorder analysis, rare variation, copy number variation, and gene-environment interplay. Findings have important implications for the development of treatment and prevention approaches and for how AN, and psychiatric and medical diseases in general, are conceptualized.
| S-EPMC6139670 | biostudies-literature
Project description:BackgroundThe purpose of this investigation was to examine heart rate variability (HRV), interbeat interval (IBI), and their interrelationship in healthy controls, bradycardic hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) mutation carriers, and patients with anorexia nervosa (AN). We tested the hypothesis that neural mechanisms cause bradycardia in patients with AN. Therefore, we assumed that saturation of the HRV/IBI relationship as a consequence of sustained parasympathetic control of the sinus node is exclusively detectable in patients with AN.MethodsPatients with AN between the ages of 12 and 16 years admitted to our hospital due to malnutrition were grouped and included in the present investigation (N = 20). A matched-pair group with healthy children and adolescents was created. Groups were matched for age and sex. A 24-hour Holter electrocardiography (ECG) was performed in controls and patients. More specifically, all patients underwent two 24-hour Holter ECG examinations (admission; refeeding treatment). Additionally, the IBI was recorded during the night in HCN4 mutation carriers (N = 4). HRV parameters were analyzed in 5-minute sequences during the night and plotted against mean corresponding IBI length. HRV, IBI, and their interrelationship were examined using Spearman's rank correlation analyses, Mann-Whitney U tests, and Wilcoxon signed-rank tests.ResultsThe relationship between IBI and HRV showed signs of saturation in patients with AN. Furthermore, signs of HRV saturation were present in two HCN4 mutation carriers. In contrast, signs of HRV saturation were not present in controls.ConclusionsThe existence of HRV saturation does not support the existence of parasympathetically mediated bradycardia. Nonneural mechanisms, such as HCN4 downregulation, may be responsible for bradycardia and HRV saturation in patients with AN.
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Project description:BackgroundAnorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment.MethodsIn this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital ( n = 30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing ( n = 30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing.ResultsThe weight (AN vs. HC, [39.31 ± 7.90] kg vs. [56.47 ± 8.88] kg, P < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ± 2.54] kg/m 2vs. [20.89 ± 2.14] kg/m 2 , P < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z = -1.981, P = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z = -2.728, P = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z = -3.638, P < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z = -2.369, P = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z = -2.115, P = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant ( P > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides , while positively correlated with Subdoligranulum . BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium.ConclusionsThe composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.
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