Psychopathology Of Anorexia Nervosa Research Articles

Early intervention for adolescents with anorexia nervosa: Pilot evaluation of an outpatient group therapy prior to inpatient treatment.

An increasing demand for inpatient treatment for adolescents with anorexia nervosa (AN) during and after the Covid-19 pandemic contrasts with limited capacity and long waiting times. The current pilot study evaluated an outpatient group therapy (GT) as early intervention for adolescents with AN prior to inpatient treatment. Seventeen female adolescents who participated at the GT (intervention group, INT) were compared to 16 adolescents without GT (treatment-as-usual, TAU). BMI, eating disorder psychopathology and motivation of change (MoC) were assessed at three timepoints. Comparing pre- versus post- group participation, we identified a significant increase of MoC and a trend towards a decreased AN-specific psychopathology. Comparing INT with TAU adolescents, we found a significant lower AN psychopathology at inpatient admission for the INT group and a trend for different BMI courses: While the BMI of the TAU group decreased during waiting time, the INT group did not show a decrease during GT resulting in a higher BMI at admission. Results of the current pilot study suggest positive effects of an early outpatient intervention in a group setting for adolescents with AN prior to inpatient treatment. Further research with larger sample sizes is necessary to validate the current pilot results.

Assessing midbrain neuromelanin and its relationship to reward learning in anorexia nervosa: Stage 1 of a registered report.

Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin-sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin-a by-product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward-related processes, may provide critical insights into reward circuit function in AN. This study will incorporate neuromelanin-sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N=30), those with weight-restored AN (N=30), and age-matched healthy controls (N=30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin-sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. This study will be among the first to interrogate midbrain neuromelanin in AN-a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

A multi-modal assessment of fear conditioning in adolescent anorexia nervosa.

Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN. Adolescent girls (Mage = 14.6 years, ±1.57) with DSM-5 diagnoses of AN (N = 25) and age-matched control girls (Mage = 14.8 years, ±1.46) with no DSM-5 diagnoses (N = 25) completed structured clinical interviews and participated in a classical three-phase Pavlovian fear conditioning paradigm. Participants with comorbid anxiety disorders were excluded. Skin conductance response (SCR) was measured, alongside self-reported fear, valence, and fear expectancy ratings. Both groups demonstrated significant differential acquisition across all four measures. Regarding group comparisons, no differences emerged for self-reported fear, valence, and fear expectancy ratings during acquisition, although for SCR, those with AN demonstrated reduced physiological arousal relative to controls. Both groups demonstrated significant differential extinction for unconditioned stimuli (US) expectancy, self-report fear, and self-report valence. No statistically significant group differences were evident during extinction to the conditioned stimuli (CS)+, on any outcome measure. However, controls reported more positive valence to the CS- than those with AN. Contrary to our hypotheses, our preliminary assessment did not find support for elevated fear responding among adolescent girls with AN with regards to fear acquisition or extinction. These data suggest that AN in adolescent girls may not be associated with a heightened propensity to acquire fear, but conversely, may suggest that exposure treatments for AN may be helpful, since extinction learning is intact in AN. AN is characterized by fear-related symptoms, including food and weight-related fear, and behavioral avoidance, yet controlled studies assessing fear learning are limited. Our preliminary assessment of adolescent AN indicates no abnormalities in fear learning among adolescents with AN. These findings may inform existing mechanistic models of AN psychopathology, and the development of exposure-based treatments for AN.

Psychopathology of anorexia nervosa: a defence from depression. An interpretation according to Massimo Fagioli’s Human Birth Theory – two case reports

This paper focuses on anorexia nervosa with an emphasis on its onset and treatment, and it particularly addresses two aspects of the disease, which seem completely in contrast with one another – prolonged fasting and recurrent episodes of binge eating/purging behaviour. From a psychopathological viewpoint, these can be considered two symptoms of the same disease, whose psychopathological core is often depression. The anorexic phase is characterised by control of food intake and interpersonal relationships due to a paralysis of affections and mental rigidity, which often provide a schizoid defence against depression and sometimes against fragmentation. In the bulimic phase, a break in this defence reveals violent and uncontrollable affects beneath depression. One possible hypothesis to evaluate would be whether these alternating phases can be overcome if they are interpreted as a false resolution of an intrapsychic conflict as defined by Fagioli’s Human Birth Theory, based on a psychic defence reaction that may arise in newborns, and which he termed annulment pulsion. If pathogenic factors are present in the first year of life, the annulment pulsion may become pathological and can explain the psychosis in anorexia nervosa patients. This paper presents two clinical cases involving two young women, one suffering from anorexia nervosa purging type with self-induced vomiting complicated by comorbid drug abuse and the other suffering from anorexia nervosa binge eating/purging type and comorbid drug and alcohol abuse. Both were successfully treated with psychodynamic psychotherapy (individual and in groups) based on the interpretation of dreams according to Human Birth Theory, which posits that a dream is a thought expressing itself through images. The patients were treated for 4 and 5 years, respectively. The scores on three standardised tools, Eating Disorder Inventory-3, Symptom Checklist-90-Revised and Toronto Alexithymia Scale, administered before and at the end of treatment, accurately reflected their baseline condition and their clinical improvement. The treatment induced a reduction or resolution of symptoms and a qualitative improvement in the patients’ oneiric activity. The encouraging outcomes for these patients support the interpretative hypothesis proposed in this article and the value of the approach based on Human Birth Theory in treating anorexia nervosa. Further work on the subject is clearly warranted.

Low oxytocin levels are broadly associated with more pronounced psychopathology in anorexia nervosa with primarily restricting but not binge/purge eating behavior.

Anorexia nervosa (AN) is commonly associated with depression, anxiety, and deficits in socioemotional functioning. Basal levels of oxytocin, a neurohormone with antidepressant, anxiolytic, and prosocial properties, are low in women with AN. However, the relationship between oxytocin and psychopathology of AN/atypical AN has not been examined in individuals with primarily food restriction (AN/AtypAN-R) or those with restriction plus binge/purge behaviors (AN/AtypAN-BP) alone, which is important to further elucidate the neurobiology of different AN presentations. We investigated whether oxytocin levels are related to eating, affective, and socioemotional psychopathology in women with AN/AtypAN-R and separately AN/AtypAN-BP. In a cross-sectional study of 53 women with low-weight AN or atypical AN based on DSM-5 (AN/AtypAN-R: n=21, AN/AtypAN-BP: n=32), we obtained fasting serum oxytocin levels and self-report measures of psychopathology, including the Eating Disorder Examination-Questionnaire (EDE-Q), Beck Depression Inventory-IA (BDI), State-Trait Anxiety Inventory (STAI), and Toronto Alexithymia Scale (TAS-20). In individuals with AN/AtypAN-R, oxytocin levels were negatively associated with eating psychopathology (EDE-Q Global Score: r=-0.49, p=0.024), depressive and anxiety symptoms (BDI Total Score: r=-0.55, p=0.009; STAI Trait Score: r=-0.63, p=0.002), and socioemotional symptoms (TAS-20 Difficulty Identifying Feelings Score: r=-0.49, p=0.023). In contrast, in those with AN/AtypAN-BP oxytocin levels were negatively associated with depressive symptoms only (BDI Total Score: r=-0.52, p=0.049). These findings support the notion that AN/AtypAN-R and AN/AtypAN-BP might have divergent underlying neurobiology. Understanding these differences is crucial to develop targeted treatments for a population with high levels of chronicity, for which no specific pharmacological treatments are currently available. https://clinicaltrials.gov, identifier: NCT01121211.

The network analysis in patients with anorexia nervosa treated with intensive enhanced cognitive behavior therapy: reflections on the research data

The network theory conceptualizes mental disorders as causally connected symptom systems rather than as effects of a superordinate and unknowable illness, otherwise called latent. Network analysis, a statistical technique designed to identify network structures among psychiatric symptoms from empirical data, has been widely used in eating disorders. Three of these studies have been conducted on patients with anorexia nervosa treated with intensive enhanced cognitive behavior therapy (CBT-E). The first study found that the network structures in adult and adolescent patients with anorexia nervosa are similar and share overvaluation of shape and weight as the core feature of anorexia nervosa psychopathology, supporting the cognitive behavioral theory. The second study found that intensive CBT-E reduces the psychopathology network connectivity over time in patients with anorexia nervosa, confirming the effectiveness of CBT-E in improving eating-disorder psychopathology. In contrast, the third study, including in the networks not only the clinical features of the eating disorder psychopathology but also those of the general psychopathology, found that the structure of the network of patients with anorexia nervosa remains unchanged mainly after intensive CBT-E. These findings stimulate a rethinking of the current viewing of the eating-disorder psychopathology and the potential reasons for the partial efficacy of actual therapeutic interventions for patients with anorexia nervosa, which seem not effective enough to break the bonds between specific and nonspecific eating disorder features.

Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation.

Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.

Genetic investigation of the contribution of body composition to anorexia nervosa in an electronic health record setting

Anorexia nervosa (AN) is a psychiatric disorder defined by anthropometric symptoms, such as low body weight, and cognitive-behavioral symptoms, such as restricted eating, fear of weight gain, and distorted body image. Recent studies have identified a genetic association between AN and metabolic/anthropometric factors, including body mass index (BMI). Although the reported associations may be under pleiotropic genetic influences, they may represent independent risk factors for AN. Here we examined the independent contributions of genetic predisposition to low body weight and polygenic risk (PRS) for AN in a clinical population (Vanderbilt University Medical Center biobank, BioVU). We fitted logistic and linear regression models in a retrospective case-control design (123 AN patients, 615 age-matched controls). We replicated the genetic correlations between PRSBMI and AN (p = 1.12 × 10−3, OR = 0.96), but this correlation disappeared when controlling for lowest BMI (p = 0.84, OR = 1.00). Additionally, we performed a phenome-wide association analysis of the PRSAN and found that the associations with metabolic phenotypes were attenuated when controlling for PRSBMI. These findings suggest that the genetic association between BMI and AN may be a consequence of the weight-related diagnostic criteria for AN and that genetically regulated anthropometric traits (like BMI) may be independent of AN psychopathology. If so, individuals with cognitive-behavioral symptomatology suggestive of AN, but with a higher PRSBMI, may be under-diagnosed given current diagnostic criteria. Furthermore, PRSBMI may serve as an independent risk factor for weight loss and weight gain during recovery.

Suicidality in adolescents with onset of anorexia nervosa.

The mortality rate in patients with anorexia nervosa (AN) is 5 to 10times higher than in general population and, suicide is one of the main causes of death. We evaluated the prevalence of suicidality (ideation, self-injurious behaviour, suicidal attempts) in 100 adolescents with onset of AN and we explored the correlation between suicidality, severity of AN symptoms and psychiatric comorbidity. We subdivided AN patients into restrictive (R-AN; n = 66) and restrictive atypical (A-AN; n = 34), according to the European Guidelines criteria. Assessment was performed using the eating disorder inventory 3rd version, the schedule for affective disorders and schizophrenia for school-age children-present and lifetime version interview, and the Columbia-suicide severity rating scale. Fisher's exact test and Mann-Whitney test (with correction for multiple testing) were used to compare the distribution of categorical and continuous variables between R-AN and A-AN patients, and between patients with vs. without suicidal behaviours. Twenty-seven patients (27%) presented suicidality as clinical feature, expressed as at least one of the following: suicidal ideation (24%), self-cutting (19%), and suicidal attempt (6%). Patients with suicidality showed greater severity of psychiatric symptoms related to AN psychopathology and presented psychiatric comorbidity, especially depression, more often than patients who did not reported suicidality (70,4% vs 29,6%). No significant differences in terms of suicidal behaviours and AN-specific psychopathology were found between R-AN and A-AN. Suicidality in adolescent patients with R-AN and A-AN seems to be related to ED symptoms. These data highlight the importance of screening for suicidality among adolescents at onset of AN, and confirms that A-AN should not be considered a milder disease. Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).

Timing of Psychopharmacological and Nutritional Interventions in the Inpatient Treatment of Anorexia Nervosa: An Observational Study.

This study aims to investigate possible different outcomes in the inpatient treatment of anorexia nervosa (AN) related to different timings of psychopharmacological and nutritional interventions. A retrospective observational study was conducted, involving young patients hospitalized for AN, treated with naso-gastric tube feeding (NGT). Participants were divided into five groups according to early (0–7 days) or late (8+ days) introduction of atypical antipsychotics (AAP) and NGT: early AAP-early NGT (EE), early AAP-late NGT (EL), late AAP-early NGT (LE), late AAP-late NGT (LL) and a control group treated with NGT only (NGT). Concurrent clinical and treatment variables were analyzed. AN psychopathology was measured with the Eating Disorder Inventory-3 (EDI-3) EDRC score. Outcomes were assessed as admission-discharge body-mass index (BMI) improvement and length of hospital stay (LOS). Contributions of variables related to outcomes were assessed with multifactorial-analyses of variance (MANOVA). Seventy-nine patients were enrolled in the study. LOS was different among treatment groups (F (4, 75) = 5.993, p < 0.001), and EE patients showed lower LOS than LE (p < 0.001) and LL (p = 0.025) patients. BMI improvement was not significantly different among treatment groups but correlated negatively with age (F (1, 72) = 10.130, p = 0.002), and admission BMI (F (1, 72) = 14.681, p < 0.001). In conclusion, patients treated with early AAP and early NGT showed lower LOS than those treated with late AAP. Prognostic treatment variables should be investigated in wider samples.

Feeling imperfect and imperfectly feeling: A network analysis on perfectionism, interoceptive sensibility, and eating symptomatology in anorexia nervosa.

In recent years, the network analysis (NA) methodology has been applied to identify the central features of the psychopathology of anorexia nervosa (AN) and specific connections to previously recognized vulnerabilities. However, an NA investigating both multidimensional perfectionism and interoceptive sensibility in connection to eating symptomatology is currently missing. A total of 260 individuals (139 patients with AN, 121 healthy control individuals) completed the Frost Multidimensional Perfectionism Scale, the Multidimensional Assessment of Interoceptive Awareness and the Eating Disorders Inventory-2. Using state-of-the-art techniques, we estimated a main network with data from all participants and then compared the two separated networks. We checked the variables for empirical overlap through goldbricker, combined as suggested and implemented the empirical measure of the bridge nodes. Ineffectiveness and need for control over self and body (resulting from combining Asceticism and Drive for Thinness) were the most central nodes, whereas perfectionistic evaluative concerns (resulting from combining Doubts about Actions and Concern over Mistakes) and mistrust in body sensations were the bridge nodes. No significant differences between the patient and control networks emerged. Perfectionistic evaluative concerns and mistrust in body sensations could be key components in the relationships among perfectionism, interoceptive sensibility and eating symptomatology.

Does local cerebellar volume predict treatment success in anorexia nervosa?

Anorexia nervosa (AN) is difficult to treat with up to half of patients failing to gain weight during treatment. Neurobiological factors predicting treatment response in AN are poorly understood. In this longitudinal study, we aimed to identify morphological characteristics in the grey matter which predict treatment success in patients with AN. Fifty patients with severe AN participated in an eating disorder-specific inpatient treatment. On admission, T1-weighted magnetic resonance images were acquired from all patients. Half of the patients successfully gained weight, reaching a body-mass index ≥ 17.5 kg/m2. Using voxel-based morphometry, local grey matter volumes were compared between the two groups of patients who gained weight and those who did not. This approach allowed us to identify anatomical characteristics which predict treatment success in terms of post-treatment weight status. Patients who did not reach the weight threshold at discharge had a smaller volume in the right cerebellar crus I at the time of admission. In this group, smaller volume was associated with a greater alexithymia score. The findings suggest that a trophic state within the cerebellum before treatment might be prognostic for treatment success. Consistent with previous reports, this result further substantiates the possible role of the cerebellum in the psychopathology of AN.

Feasibility and acceptability of home treatment as an add-on to family based therapy for adolescents with anorexia nervosa. A case series.

ObjectiveThis study examines the feasibility, acceptability, and preliminary effect sizes on outcome measures of home treatment (HT) as an add‐on to family‐based therapy (FBT) in adolescents with anorexia nervosa (AN). The HT intervention is delivered by specialized nurses and aims at supporting patients and parents to re‐establish family meals in the home environment.MethodForty‐five (43 female, 2 male) adolescents meeting ICD 10 criteria for anorexia nervosa or atypical anorexia nervosa received FBT augmented with HT over 12 weeks. Eating disorder (ED) diagnosis, psychopathology and severity of clinical symptoms were assessed using the Eating Disorder Examination (EDE) interview, the Eating Disorders Inventory (EDI‐2) at baseline (BL) and after 3‐monthsResultsAll participants and parents were retained and found HT acceptable. At the end of Treatment (EOT) participants showed a significant early weight gain, a reduction in the AN psychopathology assessed with the EDE interview and a reduction in EDI‐2 total scores. None of the patients had to be admitted to hospital. Treatment satisfaction was high in both patients and parents.DiscussionFindings provide preliminary evidence that HT is feasible, acceptable and produces clinically significant improvements in targeted outcome.

From Desire to Dread-A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa.

Anorexia nervosa is a severe psychiatric illness associated with food avoidance. Animal models from Berridge et al. over the past decade showed that environmental ambience, pleasant or fear inducing, can trigger either appetitive (desire) or avoidance (dread) behaviors in animals via frontal cortex, nucleus accumbens dopamine D1 and D2 receptors, and hypothalamus. Those mechanisms could be relevant for understanding anorexia nervosa. However, models that translate animal research to explain the psychopathology of anorexia nervosa are sparse. This article reviews animal and human research to find evidence for whether this model can explain food avoidance behaviors in anorexia nervosa. Research on anorexia nervosa suggests fear conditioning to food, activation of the corticostriatal brain circuitry, sensitization of ventral striatal dopamine response, and alterations in hypothalamic function. The results support the applicability of the animal neurocircuitry derived model and provide directions to further study the pathophysiology that underlies anorexia nervosa.

Confidence in one-self and confidence in one's own body: The revival of an old paradigm for anorexia nervosa.

Impaired interoceptive function represents an important variable in the psychopathology of anorexia nervosa (AN) and is thought to be influenced by maladaptive schemas grounded on early intimate interactions. However, the role of the different psychological processes involved in the interoceptive function has been poorly assessed in AN. We aimed to investigate the associations between adult insecure attachment, interoceptive processes, and psychopathology. One hundred and fifty participants with AN completed self-report questionnaires: the Multidimensional Assessment of Interoceptive Awareness, which measures interoception dimensions; the Attachment Style Questionnaire, assessing adult attachment styles, and the Eating Disorder Inventory-2, exploring eating-related core symptoms. Pearson's correlations were employed to assess the relationships between MAIA and EDI-2 subscores. Structural equation models (SEM) were performed to investigate the relationships between insecure attachment dimensions, interoception, and AN core symptoms as latent variables. Body listening, self-regulating, and trusting were interoceptive dimensions associated with eating psychopathology. As confirmed by an exploratory factor analysis, these interoceptive dimensions are included in a latent variable which points to "confidence" in body sensations. SEM showed that insecure, in particular anxious, attachment predicts body "confidence" and, in turn, AN core symptoms. Confidence in body sensations as a trustworthy source of knowledge represents the specific interoceptive dimension associated with psychopathology in AN. In accordance with Bruch's model of AN, insecure attachment patterns may promote a need to validate inner experiences by external sources conferring vulnerability to symptomatology. These psychopathological pathways could be addressed in clinical interventions.

Neuroanatomical signatures of anorexia nervosa psychopathology: An exploratory MRI/DTI study in a mixed sample enriched for disease vulnerability

Neuroanatomical signatures of anorexia nervosa psychopathology: An exploratory MRI/DTI study in a mixed sample enriched for disease vulnerability

Positive emotion and motivational dynamics in anorexia nervosa: A positive emotion amplification model (PE-AMP).

The role of positive emotion in anorexia nervosa (AN) has been underappreciated in both theory and treatment. Yet, people with AN demonstrate high motivation for and sustained effort toward weight loss, achieving success to an extreme beyond the capability of most people. Positive emotion dysregulation may facilitate and reinforce such efforts. The positive emotion amplification (PE-AMP) model of AN describes a dynamic interplay between biologically based enhanced reward responding and cognitive-behavioral factors that amplify positive emotion, resulting in positive feedback cycles that motivate and reinforce weight loss behavior during the AN onset phase. These experiences subvert the pursuit of happiness by providing artificial senses of autonomy, competency, and relatedness to others (self-determination theory; Ryan & Deci, 2000) that provide a stark contrast to an otherwise negative emotional environment, resulting in the emergence and persistence of AN psychopathology as a self-sustaining sense of purpose. Ultimately, negative emotion, PE dysregulation, and artificial self-determination threats continue to drive AN behavior during the AN maintenance phase, pushing patients toward a genuine self-determination breakdown that can lead to hospitalization, health crises, relational strife and diminished quality of life, or even manifest in suicidal behavior. Future research directions and novel methodological approaches inspired by the PE-AMP model are discussed, as are important treatment implications for addressing this highly treatment-resistant disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Potential shortcomings in current studies on the effect of intranasal oxytocin in Anorexia Nervosa and healthy controls - A systematic review and meta-analysis.

The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.

Pharmacological treatment of acute-phase anorexia nervosa: Evidence from randomized controlled trials.

Anorexia nervosa (AN) is the psychiatric disorder with the highest mortality rate, with a standard mortality ratio of 5.86. Despite the large use of psychotropic drugs in the clinical setting, Food and Drug Administration has not approved any psychoactive treatment for AN. The aim of this study was to perform an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) investigating psychopharmacological treatment in acute-phase AN. The present paper follows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. An extensive literature search was performed. All RCTs enrolling patients with acute-phase AN, comparing at least one psychotropic drug with another drug, placebo, treatment-as-usual or no treatment were included. The main outcome was the effect of psychoactive drugs on body mass index (BMI); data on psychopathological outcomes were also collected when available. A total of 19 RCTs met all specified criteria. Of these, 11 were excluded from quantitative analyses. Of the eight studies included in the meta-analyses, five reported data on BMI, showing no significant difference between olanzapine and placebo for weight recovery. No significant result was found for AN psychopathology, depressive and anxious symptoms for any of the molecules studied. RCTs published in this field display methodological biases, low sample sizes and short follow-up periods. Further research efforts are needed in this field as no evidence has been demonstrated for the use of any psychotropic drug in acute-phase AN neither for weight recovery, nor for comorbid psychiatric symptoms.

Peripheral serotonin transporter DNA methylation is linked to increased salience network connectivity in females with anorexia nervosa

Epigenetic variation in the serotonin transporter gene (SLC6A4) has been shown to modulate the functioning of brain circuitry associated with the salience network and may heighten the risk for mental illness. This study is, to our knowledge, the first to test this epigenome–brain–behaviour pathway in patients with anorexia nervosa. We obtained resting-state functional connectivity (rsFC) data and blood samples from 55 acutely underweight female patients with anorexia nervosa and 55 age-matched female healthy controls. We decomposed imaging data using independent component analysis. We used bisulfite pyrosequencing to analyze blood DNA methylation within the promoter region of SLC6A4. We then explored salience network rsFC patterns in the group × methylation interaction. We identified a positive relationship between SLC6A4 methylation levels and rsFC between the dorsolateral prefrontal cortex and the salience network in patients with anorexia nervosa compared to healthy controls. Increased rsFC in the salience network mediated the link between SLC6A4 methylation and eating disorder symptoms in patients with anorexia nervosa. We confirmed findings of rsFC alterations for CpG-specific methylation at a locus with evidence of methylation correspondence between brain and blood tissue. This study was cross-sectional in nature, the sample size was modest for the method and methylation levels were measured peripherally, so findings cannot be fully generalized to brain tissue. This study sheds light on the neurobiological process of how epigenetic variation in the SLC6A4 gene may relate to rsFC in the salience network that is linked to psychopathology in anorexia nervosa.