Exploring Alcohol-Related Behaviours in an Adult Sample with Anorexia Nervosa and Those in Recovery.

While individuals with Bulimia Nervosa (BN) and Binge Eating Disorder (BED) often present with a higher rate of Alcohol Use Disorder (AUD) than the general population, it is unclear whether this extends to AN. This cross-sectional study examined differences in alcohol-related behaviours, measured using the Alcohol Use Identification Test (AUDIT), between AN participants (n = 58), recovered AN (rec-AN) participants (n = 25), and healthy controls (n = 57). Statistical models controlled for age and ethnicity. The relationship between alcohol-related behaviours with ED psychopathology and with depression was also assessed. The findings indicated that acute AN participants were not at greater risk of AUD than healthy controls. However, rec-AN participants displayed greater total audit scores than those with acute AN, and more alcohol-related behaviours than healthy controls. Acute AN participants consumed significantly less alcohol than both the healthy control group and rec-AN group. No associations were found between ED psychopathology and alcohol-related behaviours in the AN group or rec-AN. This highlights alcohol as a potential coping mechanism following AN recovery. Clinicians should consider assessments for AUD and targeted interventions aimed at encouraging healthy coping mechanisms in this group. Future studies should look at alcohol use as a moderating factor for AN recovery.

Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Disentangling the effects of depression and perceived stress on cortisol levels in individuals with obesity: Preliminary results from a cross-sectional study.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been suggested to play a role in the association between depression and obesity. The study aimed to investigate differences in cortisol levels in individuals with obesity with and without depression and the role of perceived stress on these differences. METHODS: Saliva samples were collected at awakening, 15-, 30- and 60-minutes post-awakening from 66 individuals with obesity (30 with major depressive disorder and 36 without major depressive disorder). Salivary cortisol was analysed using ELISA technique. Linear Mixed Models were used for group differences in cortisol awakening response (CAR) with adjustment for socio-demographic confounders and binge eating. RESULTS: Individuals with obesity and depression had lower CAR compared with individuals with obesity without depression (ß = -0.44; p = 0.036). When controlling for perceived stress, CAR was no longer influenced by depression (ß = -0.09; p = 0.75), but individuals with moderate/high stress had lower CAR compared with those with low stress (ß = -0.63; p = 0.036). CONCLUSIONS: Our results suggest that differences in CAR between individuals with obesity with and without depression could be due to higher levels of perceived stress in the depressed subjects.

Evaluation of film stimuli for the assessment of social-emotional processing: a pilot study.

Background: Difficulties in top-down and bottom-up emotion generation have been proposed to play a key role in the progression of psychiatric disorders. The aim of the current study was to develop more ecologically valid measures of top-down interpretation biases and bottom-up evoked emotional responses. Methods: A total of 124 healthy female participants aged 18-25 took part in the study. We evaluated two sets of 18 brief film clips. The first set of film clips presented ambiguous social situations designed to examine interpretation biases. Participants provided written interpretations of each ambiguous film clip which were subjected to sentiment analysis. We compared the films in terms of the valence of participants interpretations. The second set of film clips presented neutral and emotionally provoking social scenarios designed to elicit subjective and facial emotional responses. While viewing these film clips participants mood ratings and facial affect were recorded and analysed using exploratory factor analyses. Results: Most of the 18 ambiguous film clips were interpreted in the expected manner while still retaining some ambiguity. However, participants were more attuned to the negative cues in the ambiguous film clips and three film clips were identified as unambiguous. These films clips were deemed unsuitable for assessing interpretation bias. The exploratory factor analyses of participants' mood ratings and evoked facial affect showed that the positive and negative emotionally provoking film clips formed their own factors as expected. However, there was substantial cross-loading of the neutral film clips when participants' facial expression data was analysed. Discussion: A subset of the film clips from the two tasks could be used to assess top-down interpretation biases and bottom-up evoked emotional responses. Ambiguous negatively valenced film clips should have more subtle negative cues to avoid ceiling effects and to ensure there is enough room for interpretation.

Short communication: Serum levels of brain-derived neurotrophic factor and association with pro-inflammatory cytokines in acute and recovered anorexia nervosa.

Brain-derived neurotrophic factor (BDNF) is a neuroprotective molecule known to be involved in neuroplasticity, learning and memory. Additionally, it may mitigate the effects of inflammation on the brain. There is inconclusive evidence as to whether reductions in BDNF found in AN are related to features associated with the illness such as changes in inflammatory markers and comorbidities, and whether they persist after recovery. This cross-sectional study measured BDNF and 36 inflammatory markers in the serum of individuals recovered from AN (rec-AN; n = 24), with acute AN (n = 56), and healthy controls (n = 51). We (a) compared BDNF concentrations between AN, rec-AN and controls including four pre-determined covariates; (b) assessed the relationship between BDNF and body mass index, eating disorder (ED) psychopathology and depression; and (c) correlated BDNF with inflammatory markers, stratified by group. The AN group showed reductions in BDNF compared to controls and rec-AN. BDNF was negatively associated with depression and ED psychopathology in the whole sample, but not the AN sample. BDNF was positively correlated with three inflammatory markers in the control group (interleukin (IL)-8, Eotaxin-3, tumor necrosis factor (TNF)-α) and negatively correlated with one (IL-16). The only pro-inflammatory marker associated with BDNF in the AN group was TNF-α, and no pro-inflammatory markers were associated with BDNF in the rec-AN group. These results indicate that BDNF serum concentrations may be a state marker of AN. In people with acute AN, BDNF levels seem to be linked to TNF-α signalling. However, BDNF concentrations do not appear to reflect AN symptom severity.

Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa.

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII®) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Reduced MIP-1ß as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa.

Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1ß were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1ß may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.

Attitudes Surrounding Music of Patients With Anorexia Nervosa: A Survey-Based Mixed-Methods Analysis.

Anorexia nervosa (AN) is one of the main eating disorders. It has the highest mortality of all psychiatric disorders, and the success rates of current therapies are not fully satisfactory. Thus, there is a need for novel interventions. We investigated the attitudes surrounding music of 41 patients with clinically-diagnosed AN as well as their thoughts on the potential therapeutic uses of music using a questionnaire of 50 questions. Free text responses were qualitatively analyzed for reoccurring themes with NVivo 12 software. Yes/no questions and questions of best fit were analyzed using the IBM SPSS Statistics version 25. The most prevalent theme was the positive effect of music. Most patients reported that listening to music evokes varying emotions in them (83%) which may be of positive or negative nature. Similarly, patients associated certain music with particular positive, but also with particular negative memories. A majority of patients stated that music helps to distract them (85%), helps with loneliness (59%) and helps them feel more connected to others (58%). This data indicates that people with AN make nonclinical use of music which seems to elicit positive as well as negative emotions and memories. Patients felt music is beneficial with regard to important aspects of AN, such as emotional problems, loneliness, and relationship difficulties. Most of them would also like to attend music therapy.

Diet, Obesity, and Depression: A Systematic Review.

BACKGROUND: Obesity and depression co-occur in a significant proportion of the population. Mechanisms linking the two disorders include the immune and the endocrine system, psychological and social mechanisms. The aim of this systematic review was to ascertain whether weight loss through dietary interventions has the additional effect of ameliorating depressive symptoms in obese patients. METHODS: We systematically searched three databases (Pubmed, Medline, Embase) for longitudinal clinical trials testing a dietary intervention in people with obesity and depression or symptoms of depression. RESULTS: Twenty-four longitudinal clinical studies met the eligibility criteria with a total of 3244 included patients. Seventeen studies examined the effects of calorie-restricted diets and eight studies examined dietary supplements (two studies examined both). Only three studies examined people with a diagnosis of both obesity and depression. The majority of studies showed that interventions using a calorie-restricted diet resulted in decreases in depression scores, with effect sizes between ≈0.2 and ≈0.6. The results were less clear for dietary supplements. CONCLUSIONS: People with obesity and depression appear to be a specific subgroup of depressed patients in which calorie-restricted diets might constitute a promising personalized treatment approach. The reduction of depressive symptoms may be related to immunoendocrine and psychosocial mechanisms.

Cytokines and Water Distribution in Anorexia Nervosa.

In patients with anorexia nervosa (AN), decreased intracellular (ICW), extracellular (ECW), and total body water (TBW) as well as changes in serum cytokine concentrations have been reported. In this exploratory study, we measured body composition and serum cytokine levels in patients with AN (n = 27) and healthy controls (HCs; n = 13). Eating disorder symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDE-Q). Body composition was determined by bioimpedance analysis (BIA) which provided information on ICW, ECW, and TBW. Following blood collection, 27 cytokines and chemokines were quantified using multiplex ELISA-based technology: Eotaxin, Eotaxin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-) γ, interleukin- (IL-) 1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, interferon γ-induced protein- (IP-) 10, macrophage inflammatory protein- (MIP-) 1α, MIP-1ß, monocyte chemoattractant protein- (MCP-) 1, MCP-4, thymus and activation-regulated chemokine (TARC), TNF-α, and TNF-ß. ICW, ECW, and TBW volumes were significantly lower in patients with AN than in HCs. In the whole sample, GM-CSF, MCP-4, and IL-4 were positively, whereas IFN-γ, IL-6, and IL-10 were negatively associated with all three parameters of body water. In AN participants, we found a statistically significant negative correlation of IL-10 with ICW, ECW, and TBW. Our results suggest an interaction between body water and the cytokine system. Underlying mechanisms are unclear but may involve a loss of water from the gut, kidneys, or skin due to AN-associated inflammatory processes.

Hippocampal volume, function, and related molecular activity in anorexia nervosa: A scoping review.

INTRODUCTION: Anorexia nervosa (AN) is a serious and persistent eating disorder, characterized by severe dietary restriction and weight loss, with a third of patients developing a  severe-enduring form. The factors contributing to this progression are poorly understood, although there is evidence for impairments in neural structures such as the hippocampus, an area particularly affected by malnutrition and chronic stress. AREAS COVERED: This study aimed to map the evidence for alterations in hippocampal volume, function, and related molecular activity in anorexia nervosa. PubMed, PsycINFO, and Web of Science were searched for studies related to hippocampal function and integrity using a range of methodologies, such as neuropsychological paradigms, structural and functional magnetic resonance imaging, and analysis of blood components. EXPERT OPINION: Thirty-nine studies were included in this review. The majority were neuroimaging studies, which found hippocampus-specific volumetric and functional impairments. Neuropsychological studies showed evidence for a specific memory and learning impairments. There was some evidence for molecular abnormalities (e.g. cortisol), although these were few studies. Taken together, our review suggests that the hippocampus might be a particular region of interest when considering neurobiological approaches to understanding AN. These findings warrant further investigation and may lead to novel treatment approaches.

Effects of IL-6 Signaling Pathway Inhibition on Weight and BMI: A Systematic Review and Meta-Analysis.

Inhibitors of the IL-6 signaling pathway, such as tocilizumab, are frequently administered for the treatment of immune diseases, e.g., rheumatoid arthritis and multicentric Castleman's disease. The aim of this systematic review and meta-analysis was to ascertain the effects of IL-6 pathway inhibitors on weight and body mass index (BMI). Using PRISMA guidelines, we systematically reviewed relevant articles from three databases (PubMed, OVID, EMBASE). A random effects model was used to estimate standardized mean change (SMCC). Ten studies with a total of 1531 patients were included in the meta-analysis for weight and ten studies with a total of 1537 patients were included in the BMI meta-analysis. The most commonly administered IL-6 pathway inhibitor was tocilizumab. IL-6 pathway inhibitors were associated with increases in weight (SMCC = 0.09, p = 0.016, 95% CI [0.03, 0.14]) and BMI (SMCC = 0.10, p = 0.0001, 95% CI [0.05, 0.15]). These findings suggest that the IL-6 pathway is involved in weight regulation. Modulating IL-6 signaling may be a potential future therapeutic avenue used as an adjunct for the treatment of disorders associated with weight changes, such as cancer cachexia and anorexia nervosa.

Impact of TNF-α Inhibitors on Body Weight and BMI: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis of longitudinal studies was to ascertain to effects of TNF-α inhibitor therapy on body weight and BMI. METHODS: Three databases (PubMed, OVID, and EMBASE) were systematically searched from inception to August 2018. We identified prospective, retrospective, and randomized controlled studies in adults with immune-mediated inflammatory diseases treated with TNF-α inhibitors based on pre-specified inclusion criteria. A random-effects model was used to estimate standardised mean change (SMCC). RESULTS: Twenty-six longitudinal studies with a total of 1,245 participants were included in the meta-analysis. We found evidence for a small increase in body weight (SMCC = 0.24, p = .0006, 95% CI [0.10, 0.37]) and in BMI (SMCC = 0.26, p < .0001, 95% CI [0.13, 0.39]). On average, patients gained 0.90kg (SD = 5.13) under infliximab, 2.34kg (D = 5.65) under etanercept and 2.27kg (SD = 4.69) during treatment with adalimumab within the duration of the respective studies (4-104 weeks). CONCLUSION: Our results yield further support the for the view that TNF-α inhibitors increase body weight and BMI as a potential side effect. Modulating cytokine signaling could be a future therapeutic mechanism to treat disorders associated with weight changes such as anorexia nervosa.

Phosphatidylcholine Containing Long Chain Omega-3 Fatty Acids: a Treatment Adjunct for Patients with Anorexia Nervosa?

BACKGROUND: Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no drug therapy approved for AN. METHODS: We performed a narrative literature review to consider whether a choline-containing molecule, such as phosphatidylcholine (PC), with an omega (ω)-3 long chain polyunsaturated fatty acid (LCPUFA) could be a potential future medicinal treatment for AN. RESULTS: Choline and LCPUFAs have individually shown benefit for mental health. Case series and pilot studies suggest ω-3 LCPUFAs may be effective in eating disorders. However, pharmacodynamic and pharmacokinetic considerations suggest a greater benefit from the combination of both components. CONCLUSION: The combination of a choline-containing molecule with an ω-3 LCPUFA may be clinically effective and well tolerated. This idea is supported by the current literature on the role of inflammation, the microbiome, the gut-brain-axis, hormonal, neurotransmitter and intracellular signalling, and on the structure and fluidity of nerve cells membranes in patients with AN.

Water supplementation after dehydration improves judgment and decision-making performance.

Previous research has shown that dehydration and water supplementation affect mood and cognitive performance in both adults and children on a variety of tasks that assess memory, attention, executive function, and speeded responses. Given the varied effects of water on cognition, this study explored potential effects of water supplementation, hydration status, and thirst on thinking and decision-making tasks. 29 adult participants undertook a battery of cognitive tests on two separate occasions after having fasted from the previous night. On one occasion, they were offered 500 ml of water to drink prior to testing. Measures of urine osmolality confirmed the group-level effectiveness of the dehydration manipulation. Water supplementation was found to improve performance on tasks measuring cognitive reflection in judgement and decision-making. This increase in performance was associated with differences in tasks implicated in inhibition processes. Drinking water after a 12-h dehydration period increased performance in judgement and decision-making tasks, and this was not explained by differences in subjective thirst or attentiveness.

Cytokine Research in Depression: Principles, Challenges, and Open Questions.

Cytokines have been implicated in the pathology of depression. Currently, the evidence is based on cross-sectional studies and meta-analytic research comparing blood concentrations of T helper type 1 (TH1), T helper type 2 (TH2), pro-inflammatory or anti-inflammatory cytokines of patients with a depressive disorder to those of healthy controls. Additionally, multiple longitudinal studies have investigated cytokine levels during antidepressant treatment. According to the current literature, it seems that peripheral levels of interleukin (IL)-6, IL-10, IL-12, IL-13, and tumor necrosis factor (TNF)-α are elevated and that interferon (IFN)-γ levels are lower in patients with depression compared to healthy controls. However, the overlap of cytokine values between acutely depressed patients, remitted and recovered patients and healthy controls is considerable. Thus, the discriminative power of cytokine concentrations between depressed and non-depressed people is likely weak. Treatment with certain antidepressants appears to decrease peripheral levels of IL-6, IL-10, and TNF-α. However, weight gain-inducing psychopharmacological substances, such as the antidepressant mirtazapine, have been reported to potentially increase the production of pro-inflammatory cytokines. Even though cytokines are often discussed as biomarkers for depression, they have also been shown to be altered in other psychiatric disorders. Moreover, many environmental, social, psychological, biological, and medical factors are also associated with cytokine changes. Thus, cytokine alterations seem extremely unspecific. The interpretation of the results of these studies remains a challenge because it is unknown which type of cells are most responsible for cytokine changes measured in the blood nor have the main target cells or target tissues been identified. The same cytokine can be produced by multiple cell types, and the same cell can produce various cytokines. Additionally, redundancy, synergy, antagonism, and signaling cascades of cytokine signaling must be considered. Cytokines might not be associated with the diagnosis of depression according to the currently used diagnostic manuals, but rather with specific subtypes of depression, or with depressive symptoms across different psychiatric diagnoses. Therefore, the currently available diagnostic systems may not be the ideal starting point for psychiatric cytokine research.

A systematic review of in vitro cytokine production in eating disorders.

BACKGROUND: Eating disorders (EDs) have been associated with alterations in cytokine concentrations and production. This review examines whether in vitro cytokine production (i) is altered in people with EDs compared to healthy participants; and (ii) changes in response to treatment? METHODS: Using PRISMA guidelines, we systematically reviewed articles reporting group comparisons or longitudinal assessments of spontaneous and/or stimulated cytokine production in vitro in people with EDs. RESULTS: Twelve studies were included. Cross-sectional results were mixed in anorexia nervosa. Only one study measured cytokine production in bulimia nervosa. Two longitudinal studies showed that daily yoghurt consumption increases phytohemagglutinin-stimulated interferon-γ production in anorexia nervosa. CONCLUSION: The mixed results could be accounted for by variations in experimental design. Our findings suggest that cytokine production could possibly be modulated through dietary interventions. However, due to the methodological heterogeneity and shortcomings of the included studies, it seems unreasonable to draw further conclusions.