Association between childhood maltreatment and cortical folding in women with eating disorders.

Childhood maltreatment (CM) is associated with distinct clinical and biological characteristics in people with eating disorders (EDs). The measurement of local gyrification index (lGI) may help to better characterize the impact of CM on cortical structure. Thus, the present study investigated the association of CM with lGI in women with EDs. Twenty-six women with anorexia nervosa (AN) and 24 with bulimia nervosa (BN) underwent a 3T MRI scan. All participants filled in the Childhood Trauma Questionnaire. All neuroimaging data were processed by FreeSurfer. LGI maps underwent a general linear model to evaluate differences between groups with or without CM. People with AN and BN were merged together. Based on the Childhood Trauma Questionnaire cutoff scores, 24 participants were identified as maltreated and 26 as non-maltreated. Maltreated people with EDs showed a significantly lower lGI in the left middle temporal gyrus compared with non-maltreated people, whereas no differences emerged in the right hemisphere between groups. The present study showed that in people with EDs, CM is associated with reduced cortical folding in the left middle temporal gyrus, an area that could be involved in ED psychopathology. This finding corroborates the hypothesis of a 'maltreated ecophenotype', which argues that CM may allow to biologically, other than clinically, distinguish individuals with the same psychiatric disorder.

Childhood maltreatment is associated with cortical thinning in people with eating disorders.

Childhood maltreatment (CM) is a non-specific risk factor for eating disorders (ED) and is associated with a greater severity in their clinical presentation and poorer treatment outcome. These data suggest that maltreated people with ED may be biologically other than clinically different from non-maltreated people. The aim of the present study was to investigate cortical thickness (CT), a possible biomarker of neurodevelopment, in people with ED with or without history of CM and in healthy women. Twenty-four healthy women, 26 with anorexia nervosa and 24 with bulimia nervosa underwent a 3T MRI scan. All participants filled in the childhood trauma questionnaire. All neuroimaging data were processed by FreeSurfer. Twenty-four participants with ED were identified as maltreated and 26 participants with ED as non-maltreated. All healthy women were non-maltreated. Compared to healthy women, maltreated people with ED showed lower CT in the left rostral anterior cingulate gyrus, while compared to people with ED without history of CM showed lower CT values in the left superior frontal and in right caudal middle frontal and superior parietal gyri. No significant differences emerged in CT measures between healthy women and people with ED without history of CM. The present findings show for the first time that in adult people with ED childhood maltreatment is associated with cortical thinning in areas implicated in the modulation of brain processes that are acknowledged to play a role in the psychopathology of ED.

Dancing in a culture of disordered eating: A feminist poststructural analysis of body and body image among young girls in the world of dance.

Eating disorders among adolescent girls are a public health concern. Adolescent girls that participate in aesthetic sport, such as dance, are of particular concern as they experience the highest rates of clinical eating disorders. The purpose of this study is to explore the experiences of young girls in the world of competitive dance and examine how these experiences shape their relationship with the body; feminist poststructural discourse analysis was employed to critically explore this relationship. Interviews were conducted across Canada with twelve young girls in competitive dance (14-18 years of age) to better understand how the dominant discourses in the world of competitive dance constitute the beliefs, values and practices about body and body image. Environment, parents, coaches, and peers emerged as the largest influencers in shaping the young dancers' relationship with their body. These influencers were found to generate and perpetuate body image discourses that reinforce the ideal dancer's body and negative body image.

Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease.

Growth hormone secretagogue receptor 1a (GHS-R1a), which is one of the G protein-coupled receptors (GPCRs), is involved in various physiological actions such as energy consumption, growth hormone secretion promoting action, and cardiovascular protective action. The ligand was searched for as an orphan receptor for a while, but the ligand was found to be acylated ghrelin (ghrelin) discovered by Kangawa and Kojima et al. in 1999. Recently, it has also been reported that dysregulation of GHS-R1a mediates reduced feeding in various diseases. On the other hand, since the physiological effects of ghrelin have been studied exclusively in male mice, few studies have been conducted on gender differences in ghrelin reactivity. In this review, we describe (1) the characteristics of GHS-R1a, (2) the role of ghrelin in hypophagia due to stress or anticancer drugs, and (3) the gender differences in the physiological effects of GHS-R1a and the influence of stress on it.

Dysregulated Sexuality in Women with Eating Disorders: The Role of Childhood Traumatic Experiences.

The present study explored the psychopathological, behavioral, and putative biological underpinnings of dysregulated sexuality in eating disorders (EDs), focusing on the role of childhood trauma - evaluated with the Childhood Trauma Questionnaire (CTQ). The comparison between Binge-Purging and Restricting patients outlined the predominance of markers of dysregulated sexuality in the first subgroup. In the clinical sample, hypersexuality - measured through the Hypersexual Behavior Inventory (HBI) - was associated with severe psychopathology, emotion dysregulation, childhood trauma, adverse consequences, and higher ghrelin levels. Moderation analyses showed that hypersexuality was associated with emotion dysregulation and psychopathology only in those patients reporting childhood traumatic experiences.

Increased rates of eating disorders and their symptoms in women with major depressive disorder and anxiety disorders.

BACKGROUND: Individuals with eating disorders (EDs) have increased rates of major depressive disorder (MDD) and anxiety disorders. Yet, few studies have investigated rates of EDs and their symptoms in individuals presenting with MDD/anxiety disorders. Identifying potential disordered eating in people with MDD/anxiety disorders is important because even subclinical disordered eating is associated with reduced quality of life, and undiagnosed eating pathology may hinder treatment progress for both MDD/anxiety disorders and comorbid EDs. METHOD: We compared rates of EDs (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding and eating disorders) and their symptoms in 130 women with, and 405 women without, lifetime MDD or an anxiety disorder (generalized anxiety disorder, obsessive-compulsive disorder, social phobia, specific phobia, panic disorder, agoraphobia, or post-traumatic stress disorder) recruited from the population-based Michigan State University Twin Registry. Lifetime ED and MDD/anxiety diagnoses, and lifetime clinically significant disordered eating behaviors (e.g., binge eating, excessive exercise) were assessed using the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Among participants with lifetime MDD or any anxiety disorder, 13% met criteria for a lifetime ED and 39% reported engaging in at least one lifetime clinically significant disordered eating behavior (e.g., binge eating) on the SCID. In contrast, only 3% of participants without a history of MDD/an anxiety disorder met criteria for a lifetime ED, and only 11% reported lifetime clinically significant disordered eating behavior. DISCUSSION: Our findings suggest that women with MDD and anxiety disorders have elevated rates of EDs, and it is therefore imperative to screen for disordered eating in these populations.

Multivariate association between brain function and eating disorders using sparse canonical correlation analysis.

Eating disorder is highly associated with obesity and it is related to brain dysfunction as well. Still, the functional substrates of the brain associated with behavioral traits of eating disorder are underexplored. Existing neuroimaging studies have explored the association between eating disorder and brain function without using all the information provided by the eating disorder related questionnaire but by adopting summary factors. Here, we aimed to investigate the multivariate association between brain function and eating disorder at fine-grained question-level information. Our study is a retrospective secondary analysis that re-analyzed resting-state functional magnetic resonance imaging of 284 participants from the enhanced Nathan Kline Institute-Rockland Sample database. Leveraging sparse canonical correlation analysis, we associated the functional connectivity of all brain regions and all questions in the eating disorder questionnaires. We found that executive- and inhibitory control-related frontoparietal networks showed positive associations with questions of restraint eating, while brain regions involved in the reward system showed negative associations. Notably, inhibitory control-related brain regions showed a positive association with the degree of obesity. Findings were well replicated in the independent validation dataset (n = 34). The results of this study might contribute to a better understanding of brain function with respect to eating disorder.

Reward and psychopathological correlates of eating disorders: The explanatory role of leptin.

It has been hypothesized that leptin level alterations in Eating Disorders (EDs) represent a maintaining factor for pathological reward-related ED behaviors, given leptin role in the dopaminergic reward systems. The aim of the present study was to evaluate the role of leptin in EDs as a mediator for the relationship between Body Mass Index (BMI) and several pathological behaviors, such as dietary restraint, compensatory exercise, vomiting, binge eating and emotional eating. Sixty-two patients with EDs and 41 healthy controls (HC) had their blood drawn and completed psychometric tests for the evaluation of general psychopathology, ED psychopathology and emotional eating. Moderated linear regression models showed that, in the presence of high levels of ED psychopathology, leptin levels were negatively associated with dietary restraint and compensatory exercise, and positively with emotional eating and binge eating. Finally, leptin showed an indirect effect on the association between BMI and all these reward-related behaviors. These results suggest that a variation of BMI maintains these pathological ED behaviors through a variation in leptin levels. Considering the role of leptin in reward circuits, the results seem to confirm an aberrant food-related reward mechanism in ED patients.

Prevalence and psychopathology of vegetarians and vegans - Results from a representative survey in Germany.

The aim of the study was to investigate the prevalence of, and attitudes toward, vegetarianism and veganism. We also assessed the association between vegetarianism/veganism and eating disorder, depressive, and somatic symptoms. A cross-sectional questionnaire survey in adults in Germany that was representative in terms of age, gender, and educational level was carried out. Data from 2449 adults (53.5% females) were included. Mean age was 49.6 (SD 17.1) years. A total of 5.4% of participants reported following a vegetarian or vegan diet. While the majority of participants agreed that vegetarian diets are healthy and harmless (56.1%), only 34.8% believed this to be true of vegan diets. The majority of participants also believed that a vegetarian (58.7%) or vegan (74.7%) diet can lead to nutritional deficiency. Female gender, younger age, higher education, lower body mass index (BMI), and higher depressive and eating disorder symptoms were found to be associated with vegetarianism/veganism. We did not find increased physical complaints in the group of vegetarians/vegans. Our results point toward a moderate prevalence of vegetarianism/veganism among the general population. Our findings suggest that health care professionals should keep eating disorder pathology, affective status in mind when dealing with individuals who choose a vegetarian/vegan dietary pattern.

The orbitofrontal cortex, food intake and obesity

Obesity is a major health challenge facing many people throughout the world. Increased consumption of palatable, high-caloric foods is one of the major drivers of obesity. Both orexigenic and anorexic states have been thoroughly reviewed elsewhere; here, we focus on the cognitive control of feeding in the context of obesity, and how the orbitofrontal cortex (OFC) is implicated, based on data from preclinical and clinical research. The OFC is important in decision-making and has been heavily researched in neuropsychiatric illnesses such as addiction and obsessive­compulsive disorder. However, activity in the OFC has only recently been described in research into food intake, obesity and eating disorders. The OFC integrates sensory modalities such as taste, smell and vision, and it has dense reciprocal projections into thalamic, midbrain and striatal regions to fine-tune decision-making. Thus, the OFC may be anatomically and functionally situated to play a critical role in the etiology and maintenance of excess feeding behaviour. We propose that the OFC serves as an integrative hub for orchestrating motivated feeding behaviour and suggest how its neurobiology and functional output might be altered in the obese state.

Interaction between Vegetarian Versus Omnivorous Diet and Unhealthy Eating Patterns (Orthorexia Nervosa, Cognitive Restraint) and Body Mass Index in Adults.

The objective of the present study was two-fold: Firstly, to investigate unhealthy eating patterns and body mass index among individuals following a vegetarian diet and those following an omnivorous diet. Secondly, to examine interaction between vegetarian versus omnivorous diet and unhealthy eating patterns (orthorexia nervosa, cognitive restraint) and body mass index using a structural equation modeling approach (SEM). The study included 370 participants: 188 participants following a vegetarian diet and 182 following an omnivorous diet. Unhealthy eating patterns and body mass index were measured. Our results showed that individuals following a vegetarian diet were more likely to engage in orthorexic eating behavior compared to individuals following an omnivorous diet. In addition, they had a significantly lower levels of cognitive restraint and lower body mass index than individuals following an omnivorous diet. Use of SEM method showed that: (1) following a vegetarian diet and orthorexia nervosa were directly associated, (2) following an omnivorous diet and cognitive restraint were directly related and (3) following an omnivorous diet had a greater tendency to cognitive restraint and an elevated body mass index. More research is necessary to further understand the complexity of the relationship between type of diet and unhealthy eating patterns in adults.

Identifying duration criteria for eating-disorder remission and recovery through intensive modeling of longitudinal data.

OBJECTIVE: Outcome states, such as remission and recovery, include specific duration criteria for which individuals must be asymptomatic. Ideally, duration criteria provide predictive validity to outcome states by reducing symptom-return risk. However, available research is insufficient for deriving specific recommendations for remission or recovery duration criteria for eating disorders. METHOD: We intensively modeled the relation between duration criteria length and rates of remission, recovery, and subsequent symptom return in longitudinal data from a treatment-seeking sample of women with anorexia nervosa (AN) and bulimia nervosa (BN). We hypothesized that the length of the duration criterion would be inversely associated with both rates of remission and recovery and with subsequent rates of symptom return. RESULTS: Generalized estimating equations supported our hypotheses for all investigated eating-disorder features except for symptom return when using the Psychiatric Status Rating for AN. DISCUSSION: We recommend that 6 months be used for remission definitions applied to binge eating, purging, and BN symptom composite measures, whereas no duration criteria be used for low weight and AN symptom composites. We further recommend that 6 months be used for recovery definitions applied to BN symptom composites and AN symptom composites, whereas 18 months be used for individual symptoms of binge eating, purging, and low weight. The adoption of these duration criteria into comprehensive definitions of remission and recovery will increase their predictive validity, which in turn, maximizes their utility.

Bi-allelic Variants in RALGAPA1 Cause Profound Neurodevelopmental Disability, Muscular Hypotonia, Infantile Spasms, and Feeding Abnormalities.

Ral (Ras-like) GTPases play an important role in the control of cell migration and have been implicated in Ras-mediated tumorigenicity. Recently, variants in RALA were also described as a cause of intellectual disability and developmental delay, indicating the relevance of this pathway to neuropediatric diseases. Here, we report the identification of bi-allelic variants in RALGAPA1 (encoding Ral GTPase activating protein catalytic alpha subunit 1) in four unrelated individuals with profound neurodevelopmental disability, muscular hypotonia, feeding abnormalities, recurrent fever episodes, and infantile spasms . Dysplasia of corpus callosum with focal thinning of the posterior part and characteristic facial features appeared to be unifying findings. RalGAPA1 was absent in the fibroblasts derived from two affected individuals suggesting a loss-of-function effect of the RALGAPA1 variants. Consequently, RalA activity was increased in these cell lines, which is in keeping with the idea that RalGAPA1 deficiency causes a constitutive activation of RalA. Additionally, levels of RalGAPB, a scaffolding subunit of the RalGAP complex, were dramatically reduced, indicating a dysfunctional RalGAP complex. Moreover, RalGAPA1 deficiency clearly increased cell-surface levels of lipid raft components in detached fibroblasts, which might indicate that anchorage-dependence of cell growth signaling is disturbed. Our findings indicate that the dysregulation of the RalA pathway has an important impact on neuronal function and brain development. In light of the partially overlapping phenotype between RALA- and RALGAPA1-associated diseases, it appears likely that dysregulation of the RalA signaling pathway leads to a distinct group of genetic syndromes that we suggest could be named RALopathies.

Novel NGLY1 gene variants in Chinese children with global developmental delay, microcephaly, hypotonia, hypertransaminasemia, alacrimia, and feeding difficulty.

NGLY1 deficiency is the first and only autosomal recessive congenital disorder of N-linked deglycosylation (NGLY1-CDDG). To date, no patients with NGLY1 deficiency has been reported from mainland China or East Asia in English literature. Here, we present six patients with a diagnosis of NGLY1-CDDG on the basis of clinical phenotype, genetic testing, and functional studies. We retrospectively analyzed clinical phenotypes and NGLY1 genotypes of six cases from four families. Informed consent was obtained for diagnosis and treatment. In-silico tools and in vitro enzyme activity assays were used to determine pathogenicity of NGLY1 varaints. All patients had typical features of NGLY1-CDDG, including global developmental delay, microcephaly, hypotonia, hypertransaminasemia, alacrimia, and feeding difficulty. Dysmorphic features found in our patients include flat nasal bridge, loose and hollow cheeks, short stature, malnutrition, and ptosis. Pachylosis could be a novel cutaneous feature that may be explained by lack of sweat. We found three novel variants, including one missense (c.982C > G/p.Arg328Gly), one splice site (c.1003+3A > G), and one frame-shift (c.1637-1652delCATCTTTTGCTTATAT/p.Ser546PhefsTer) variant. All mutations were predicted to be disease causing with in-silico prediction tools, and affected at least one feature of gene splicing. Protein modeling showed missense variants may affect covalent bonding within the protein structure, or interrupt active/binding amino-acid residues. In vitro studies indicated that proteins carrying missense variants (p.Arg328Gly and p.Tyr342Cys) lost the enzyme activity. We expanded clinical phenotype and genetic mutation spectrum of NGLY1-CDDG by reporting six cases, three novel variants, and novel clinical features from mainland China.

Fractures in women with eating disorders-Incidence, predictive factors, and the impact of disease remission: Cohort study with background population controls.

OBJECTIVE: Malnutrition and low weight in eating disorders (EDs) are associated with increased fracture risk compared to the general population. In a cohort study, we aimed to determine fracture rates compared to age and gender matched controls (ratio 5:1), assess the impact of disease remission on fracture risk, and establish predictive factors for fractures. METHOD: Of note, 803 ED patients referred to specialized ED treatment between 1994 and 2004 were included. In 2016, data on fractures were obtained through the Danish National Registry of Patients. RESULTS: Fracture risk was increased in anorexia nervosa (AN; IRR 2.2 [CI 99%: 1.6-3.0]) but not in bulimia nervosa (BN; IRR 1.3, ns) or other specified feeding or eating disorders (OSFED; IRR 1.8, ns). IRR in the AN group were increased for vertebral fractures (IRR 3.8 [CI 99%: 1.4-10.3]), upper arm (IRR 3.0 (CI 99% 1.6-5.5) and hip (IRR 6.6 [CI 99%: 2.6-18.0]). Disease remission in AN is associated to lower fracture risk compared to active disease, but higher fracture risk compared to controls (IRR 1.7 [CI 99%: 1.1-2.7]). In regression analysis, age at debut of disease, nadir BMI and duration of disease before referral to treatment, independently predicted fracture. DISCUSSION: We confirm increased fracture risk in AN, and show significant differences in fracture risk between patients in disease remission and patients with active disease. Furthermore, we show that age at debut of disease and duration of disease before referral to treatment is positively correlated to fracture risk, whereas nadir BMI is negatively correlated to fracture risk.

Evaluating the associations between personality psychopathology and heterogeneous eating disorder behaviors: A dimensional approach.

Studies examining the associations between categorical assessments of eating disorders (ED) and personality have produced some inconsistent findings. The present study aimed to clarify these inconsistencies by implementing a dimensional approach when assessing ED behaviors and personality psychopathology. Associations between pathological personality trait facets and heterogeneous ED behaviors (i.e., restriction, compensatory behaviors, and binge eating) were examined. Participants were 570 community adults (247 women) recruited through Mechanical Turk. The Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PID-5), was used to assess the pathological personality trait facets. Items from two validated eating pathology scales were used to measure ED behaviors. Two structural equation models-an exploratory model and a theoretical model-were tested for each ED behavior. The exploratory model allowed all PID-5 personality facets to predict the ED behaviors. The theoretical models estimated paths from specific PID-5 facets to the ED behaviors. The theoretical model was an attempt to corroborate previous literature where distinct personality profiles have distinguished individuals with different EDs. The theoretical model was considered the most parsimonious model for all three ED behaviors, and each theoretical model revealed a pattern of significant associations with personality trait facets-restriction was significantly associated with higher rigid perfectionism, and binge eating was significantly associated with higher impulsivity and anxiousness. Only the significant associations with binge eating remained statistically significant when men and women were examined separately. When a dimensional model is applied, significant relationships emerge between heterogeneous ED behaviors and PID-5 trait facets. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Higher body mass index is linked to altered hypothalamic microstructure.

Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21-78 years, BMI 18-43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.

Structural differences in eating disorder psychopathology after history of childhood abuse: Insights from a Bayesian network analysis.

Childhood abuse is frequent among individuals with eating disorders and is associated with complex clinical presentations. However, to date, the differences in the presentations of eating disorders between these groups are poorly understood. The present study employed a Bayesian network approach to model the interactive network structure of eating disorder psychopathology, and to investigate the differences in symptom importance and network structure between individuals with eating disorders with and without an experience of childhood abuse in a sample 327 treatment-seeking individuals. Among individuals with a history of childhood abuse, a specific 4-symptom pathway emerged, leading from overvaluation of shape and weight and ending in overeating (overvaluation of weight and shape → loss of control → depressed mood → overeating). Loss of control eating and depressed mood emerged as the more important driving symptoms. In contrast, the eating disorder symptom network among the group with no abuse was organized around a heightened investment in weight and shape, and resulting efforts to control or alter weight and shape through dieting and exercise behaviors. The symptoms with the highest importance in this nonabuse group were overeating and overvaluation of weight and shape. These results support the existence of a distinct eating disorder symptom network characteristic of individuals with a history of childhood trauma, and add to the hypotheses of a maltreated eco-phenotype in eating disorders. They may be also inform treatment target in abused people with eating disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Associations between Comorbid TDP-43, Lewy Body Pathology, and Neuropsychiatric Symptoms in Alzheimer's Disease.

More than half of the patients with Alzheimer's disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer's Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.