Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Unveiling vocal profiles in adolescent anorexia nervosa: a Software Based, Multiparametric Analysis.

Dysphonia, characterized by disturbances in voice quality and modulation, has been sporadically observed in individuals with Anorexia Nervosa (AN), potentially stemming from both organic and psychopathological factors. This study seeks to employ software-based voice analysis to compare the voices of girls with AN to those of female healthy controls (HC). Case-control study adopting "Praat" software to assess voices. Various parameters, including Acoustic Voice Quality Index (AVQI), Fundamental Frequency (F0), Yanagihara's Spectrographic Dysphonia Classifications, and "GIRBAS" perceptual qualitative voice rating, were investigated. Participants completed questionnaires for Vocal Fatigue Index (VFI) and the Reflux Symptoms Index (RSI). Puberty-related voice spectrum changes were considered, and Bonferroni-corrected BMI-adjusted Analyses of Covariance (ANCOVAs) were conducted. The study enrolled 15 girls with AN and 23 girls with HC. AN patients demonstrated greater impairment in voice tiredness/voice avoidance (VFI-1, p < 0.001), vocal physical discomfort (VIF-2, p = 0.002), and rest as alleviation (VFI-3, p = 0.012). Reflux-related scores were higher in AN (p < 0.001). Differences were observed in voice quality (AVQI) (p = 0.001), and GIRBAS scales showed alterations in multiple parameters. Spectrograms documented more frequent pathological findings in AN patients (p = 0.021). No difference was observed in Fundamental Frequency. These group (AN/HC) differences were independent of weight measures. This study is the first to connect voice irregularities in AN by employing standardized, non-invasive tools and accounting for weight-related factors. Young AN patients demonstrated substantial voice quality changes and heightened self-reported symptoms. Future research should expand on these findings with prospective designs and invasive investigations.

Virtual Reality Exposure to a Healthy Weight Body Is a Promising Adjunct Treatment for Anorexia Nervosa.

INTRODUCTION/OBJECTIVE: Treatment results of anorexia nervosa (AN) are modest, with fear of weight gain being a strong predictor of treatment outcome and relapse. Here, we present a virtual reality (VR) setup for exposure to healthy weight and evaluate its potential as an adjunct treatment for AN. METHODS: In two studies, we investigate VR experience and clinical effects of VR exposure to higher weight in 20 women with high weight concern or shape concern and in 20 women with AN. RESULTS: In study 1, 90% of participants (18/20) reported symptoms of high arousal but verbalized low to medium levels of fear. Study 2 demonstrated that VR exposure to healthy weight induced high arousal in patients with AN and yielded a trend that four sessions of exposure improved fear of weight gain. Explorative analyses revealed three clusters of individual reactions to exposure, which need further exploration. CONCLUSIONS: VR exposure is a well-accepted and powerful tool for evoking fear of weight gain in patients with AN. We observed a statistical trend that repeated virtual exposure to healthy weight improved fear of weight gain with large effect sizes. Further studies are needed to determine the mechanisms and differential effects.

General psychopathological symptoms in children, adolescents, and young adults with anorexia nervosa-a naturalistic study on follow-up and treatment.

Recent research has assessed the role of general psychopathological symptoms in the natural history of mental health conditions, including anorexia nervosa (AN) in adults and obesity in children. Nevertheless, literature assessing general psychopathological symptoms in young patients with AN and their potential prognostic role in long-term outcomes is lacking. Observational, naturalistic study, involving young patients hospitalized for AN. General psychopathological symptoms were assessed by administering Symptom Check List-90-R (SCL-90-R) at admission (T0) and discharge (T1). AN-specific psychopathology was assessed with Eating Disorders Inventory-3 Eating Disorder Risk (EDRC) and Body Uneasiness Test Global Severity Index (BUT-GSI). Potential T0-T1 modifications of general psychopathological symptoms and their possible associations with baseline psychopathological, weight, and psychopharmacological variables were assessed with a generalized linear model (GLM), corrected for baseline SCL-90-R scores. Then, possible associations between T0 general psychopathological symptoms and the risk of re-hospitalization at 1 year were assessed with the Kaplan-Meier method and Cox regression. This study enrolled 133 patients (mean age 16.9 ± 2.9 years, F = 91.8%). A significant T0-T1 reduction (p < 0.001) in almost all the general psychopathological symptoms (except paranoia) emerged. The GLM revealed that higher EDI-3 EDRC scores were associated with higher T1 SCL-90-R scores in multiple domains. Cox regressions revealed a predictive role of SCL-90-R interpersonal sensitivity (B = 0.113, hazard ratio = 1.119, p = 0.023) on the risk of re-hospitalization at 1 year.  Conclusion: General psychopathological symptoms in young patients with AN may be influenced by hospital treatment interventions and have a potential prognostic role on post-discharge outcomes. Further longitudinal studies are required. What is Known: • General psychopathological symptoms represent a relevant feature that clinicians should consider in the diagnosis, treatment, and prognosis of multiple psychiatric conditions. Co-occurring psychiatric comorbidities, moreover, have been documented to impact individuals diagnosed with Anorexia Nervosa (AN) in the developmental age. Despite this evidence, the literature lacks studies assessing the occurrence and impact of general psychopathological symptoms in young patients with AN. What is New: • The clinical picture of children, adolescents, and young adults with AN mays be impacted by multiple general psychopathological symptoms, including Somatization, Obsession-compulsion, Interpersonal sensitivity, Depression, Anxiety, Hostility, Phobia, Paranoia, and Psychoticism, which may improve with a multidisciplinary hospital intervention. The occurrence of these symptoms, particularly "interpersonal sensitivity", may negatively impact the prognosis of the affected patients.

Premenarchal anorexia nervosa: clinical features, psychopharmacological interventions, and rehospitalization analysis in a 1-year follow-up, controlled study.

Premenarchal anorexia nervosa (AN) represents a specific subtype of AN, defined by an onset before the menarche in females, involving unique endocrine and prognostic features. The scarce data on this condition lack case-control and follow-up studies. This is a case-control, observational, naturalistic study, involving participants with premenarchal AN (premenarchal girls presenting to the study center newly diagnosed with AN) treated with a multidisciplinary hospital intervention, compared to postmenarchal AN individuals on clinical, endocrine, psychopathological, and treatment variables. The rate of rehospitalizations on a 1-year follow-up after discharge and respective prognostic factors were assessed with a Kaplan-Meier analysis and Cox regression model. The sample included 234 AN participants (43, 18.4% with premenarchal and 191, 81.6% with postmenarchal AN). When compared to postmenarchal, premenarchal AN individuals presented with lower depressive scores (Self-Administered Psychiatric Scales for Children and Adolescents (SAFA)) (U = 1387.0, p = 0.010) and lower luteinizing hormone (LH) levels (U = 3056.0, p = 0.009) and were less frequently treated with antidepressants (X2 = 5.927, p = 0.015). A significant predictive model of the risk of rehospitalization (X2 = 19.192, p = 0.004) identified a higher age at admission (B = 0.522, p = 0.020) and a day-hospital (vs inpatient) treatment (B = 3957, p = 0.007) as predictive factors for rehospitalization at 1-year, independent from the menarchal status.   Conclusion: This study reports the clinical and treatment characteristics of premenarchal AN in one of the largest samples available in the current literature. Specific clinical features and prognostic factors for rehospitalization at 1-year follow-up were identified. Future studies should longitudinally investigate treatment-dependent modifications in endocrine and psychopathological measures in this population. What is Known: • Premenarchal Anorexia Nervosa (AN) is a subtype of AN characterized by its onset before menarche in females and is associated with unique endocrine and prognostic features. What is New: • Individuals with premenarchal AN may display specific clinical profiles, with lower depressive symptoms and luteinizing hormone levels than postmenarchal controls.

Clinical and psychopathological profiles of children with somatic symptom disorders in a pediatric emergency unit: an observational study before and during the SARS-CoV-2 pandemic.

Somatic symptom disorders (SSDs) are a group of clinical conditions characterized by heterogeneous physical symptoms, not directly supported by a demonstrable organic process. Despite representing a growing problem in the pediatric age, the literature lacks studies assessing the psychopathological and clinical features of subjects with SSD, particularly during the SARS-CoV-2 pandemic. This is a retrospective, observational study, involving two historical cohorts of children admitted to a tertiary referral Italian hospital over the 2 years preceding and following the start of the SARS-CoV-2 pandemic. Demographic, clinical, socio-economical, and psychological variables were investigated. Standardized tests for the developmental age were administered to assess psychopathological variables. Overall rates and trends of accesses for SSD, as compared to the total accesses for any cause at the Pediatric Emergency Room during the same periods, were reported as well. Fifty-one (pre-pandemic, 29; pandemic, 22) children with SSD were enrolled (age, 11.4 ± 2.4 years, F = 66.7%). Subjects in the pandemic historical cohort reported more frequently fever (p < 0.001), headache (p = 0.032), and asthenia (p < 0.001), as well as more chronic conditions in personal and family history, and fewer previous hospital accesses, as compared to the pre-pandemic cohort. Depressed mood and anxious traits were documented in both samples. None of them had an ongoing or a previously reported SARS-CoV-2 infection. During the pandemic, a clinical psychologist was more frequently consulted before the hospital discharge to mental health services, to support the diagnosis.  Conclusion: This study showed the significant burden of SSD in children, highlighting the need to implement pediatricians' education to optimize the management of these patients. Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features. Future studies, conducted on longitudinal and controlled samples, are indicated to further investigate children with these conditions. What is Known:    â€¢ Somatic symptoms disorders (SSDs) are frequent in the pediatric age, especially in early adolescence.    â€¢ Evidence remains scarce on the impact of the SARS-CoV-2 pandemic on SSDs in children. What is New:    â€¢ Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features.    â€¢ The implementation of pediatricians' education and a multidisciplinary approach are needed to optimize the management of SSDs.

The Role of Mood Stabilizers in Children and Adolescents with Anorexia Nervosa: A 1-year Follow-Up, Propensity Score-Matched Study.

BACKGROUND: The existing literature on the use of mood stabilizers (MS) in children and adolescents with anorexia nervosa (AN) is limited, for the most part, to small case studies. METHODS: This was an observational, naturalistic, propensity score-matched study. Subjects treated and not-treated with MS were compared by being matched via propensity score on age, sex, concurrent atypical antipsychotics, and concurrent antidepressants. General and AN-specific psychopathology was assessed with Symptom Check List-90-R, Beck Depression Inventory-II, Eating Disorders Inventory-3, and Body Uneasiness Test-A. Potential differences in admission-discharge modifications (body mass index (BMI), psychopathology) among the two groups were assessed. Finally, re-hospitalizations after 1-year follow-up were assessed with Kaplan-Meier analyses. RESULTS: The study enrolled 234 hospitalized patients (15.9+/-3.3 years; 26, 11.1% receiving MS). After propensity-score matching, 26 MS patients matched with 26 MS-not-treated subjects were included. MS were used for a mean of 126.1 (+/-87.3) days, and two cases of side effects were documented (alopecia and somnolence with valproate). No significant difference between MS-treated and not-treated patients emerged concerning admission-discharge improvements in BMI and AN-specific or general psychopathology. The cumulative survival from re-hospitalization at 12 months was 64,4% (95%-CI, 31.3-97.5) for MS and 58.7% (95%-CI, 22.2-95.2) for MS-not-treated subjects. No significant difference in survival rate emerged (hazard ratio, 0.04; Log-rank test: p=0.846). CONCLUSIONS: This propensity score-matched study expands on the scant existing evidence of the use and side effects of MS in children and adolescents with AN. These results should be assessed in wider longitudinal samples.

Eating disorders in young patients with neurofibromatosis type 1.

AIM: We describe the association of neurofibromatosis type 1 (NF1) and feeding and eating disorders (FED) in five patients admitted to our third level centre for both FED and NF1. METHODS: Case series of five adolescent females with NF1 treated for FED. RESULTS: We collected data from five patients with NF1 aged between 14 and 22 years, all females. The onset of eating disorder symptoms occurred between 13 and 19 years of age and was characterised by food intake restriction, associated with physical hyperactivity in three out of five cases. One patient also reported self-injurious acts and episodic binges. Patients received diagnoses of anorexia nervosa (AN, n = 2), atypical AN (n = 1), bulimia nervosa (n = 1), unspecified feeding and eating disorder (n = 1). CONCLUSION: The current literature reports a single case of an adult with NF1 and comorbid AN, focusing on the dermatological features of NF1. Our article describes a case series of five patients in developmental age affected by NF1 and FED. Clinical and psychological features of NF1 may play a role in the pathogenesis of FED when these two conditions co-occur. The dermatological alterations of NF1 may contribute to body image distortion that characterises AN. Further research is required to systematically screen populations of patients with NF1 for the presence of FED.

Barriers and facilitators affecting treatment uptake behaviours for patients with eating disorders: A systematic review synthesising patient, caregiver and clinician perspectives.

OBJECTIVE: A significant treatment gap exists between persons affected by eating disorders (ED), and those engaging with treatment services. This systematic review aims to provide a thorough understanding of the barriers and facilitators affecting eating disorder treatment engagement, including a synthesis of the perspectives of patients, caregivers and healthcare professionals. METHOD: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were retrieved from three databases (PubMed, PsycInfo, Web of Science) and were screened and assessed independently by two raters. A thematic analysis was completed to determine the key barriers and facilitators reported by the included studies. RESULTS: A total of 73 studies were included. From these studies, 12 barriers and 13 facilitators were identified. Patients reported stigma, shame and guilt as the most prominent barrier affecting their engagement with treatment services. Meanwhile, caregivers and healthcare professionals reported a lack of eating disorder knowledge of clinicians as the most important barrier. Positive social support was cited as the most prominent facilitator to promote help-seeking. DISCUSSION: Patients, caregivers and healthcare professionals experience a variety of barriers and facilitators to treatment uptake for ED. Interventions addressing barriers and facilitators could increase treatment engagement, including anti-stigma campaigns and positive peer-support interventions.

Hemiplegic-Migraine-like Attacks as First Manifestation of Diffuse Leptomeningeal Glioneuronal Tumor: A Case Report.

BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a low-grade tumor characterized by diffuse leptomeningeal infiltrates. Symptoms are usually secondary to hydrocephalus. Hemiplegic migraine (HM)-like episodes have never been associated with DLGNT, but they have been reported with different inflammatory and tumoral entities involving leptomeninges. OBSERVATIONS: We report the case of a 10-year-old boy with recurrent episodes of right hyposthenia, aphasia, and headache lasting hours to days with complete remission. The electroencephalogram during the attack showed diffuse slower activity on the left hemisphere, which improved together with the symptoms. DLGNT was discovered during a follow-up magnetic resonance imaging and confirmed by biopsy. CONCLUSIONS: This is the first report of HM-like attacks in DLGNT. We discuss the pathogenetic hypotheses of our case and previously reported cases of "symptomatic" HM with leptomeningeal involvement.

Inpatient treatment of anorexia nervosa with adjunctive valproate: a case series of 14 young and adolescent patients.

BACKGROUND: The use of valproate in the treatment of Anorexia Nervosa (AN) in children and adolescents is currently not recommended by clinical guidelines, due to lack of evidence. Nonetheless, valproate is used to treat a series of psychiatric and neurologic conditions. To date, only six cases of patients with Feeding and Eating Disorders (three with AN) have been described. METHODS: Case series of 14 children and adolescent patients hospitalized for AN and treated with valproate as an adjunctive treatment. Reasons for introduction, dosages, plasma levels, adverse drug reactions (ADR) and modifications of liver enzymes, platelets levels, abdominal and pelvic ultrasounds, and concurrent drugs plasma levels were assessed. RESULTS: Reasons for the introduction of valproate included unstable mood (57.1%), lack of compliance (50%) and aggressive behaviour (21.4%). In 71.4% of patients an improvement on target symptoms was observed. Valproate was started at 241.7 (± 73.3) mg, up to 521.4 (± 204.5) mg; the most frequent scheme was twice-daily. The mean plasmatic concentration was 66.3 (± 25.0) mg/L. One patient (7.1%) experienced side effects (somnolence). No major modifications of liver enzymes, platelet levels, abdominal and pelvic ultrasounds emerged after the introduction of valproate. Low concurrent olanzapine and quetiapine levels were documented. CONCLUSIONS: This is the largest sample of patients with AN treated with valproate. Valproate was administered to improve psychiatric symptoms impairing compliance with inpatient treatment programs. The majority of patients experienced an improvement on target symptoms after being administered valproate, with minor ADR. These data should be investigated in wider populations and controlled studies. LEVEL OF EVIDENCE: Level IV, case series.

Avoidant-restrictive food intake disorder in a male patient with Goldenhar syndrome.

BACKGROUND: Goldenhar syndrome (GS) is a rare congenital condition characterized by the underdevelopment of structures deriving from the first and second branchial arches. Clinical phenotype might encompass extra-craniofacial abnormalities, and patients may experience neuropsychiatric disorders with a higher prevalence than healthy controls. To the best of our knowledge, an association between GS and Feeding and Eating Disorders (FED) has never been reported in the literature. CASE REPORT: A 15-year-old boy with GS was referred to our outpatient clinic due to severe underweight (BMI of 12.7 kg/m2) and food intake disorder with avoidant restrictive features. After a diagnosis of avoidant-restrictive food intake disorder (ARFID) was made, an inpatient multidisciplinary intervention and outpatient follow-up program were provided, which resulted in the improvement of the boy's weight and FED psychopathology. CONCLUSIONS: The current report describes the first case of a young male with GS and ARFID. We suggest that ARFID may present itself as part of the spectrum of neuropsychiatric disorders associated with the syndrome; since traumatic experiences and gastrointestinal discomfort play a pivotal role in the development of ARFID among children, attention should be paid to those affected by GS that involves crucial structures in the swallowing process. Further literature evidence will help portray the complex relationship between ARFID and GS more precisely. LEVEL OF EVIDENCE: Level V, case report.

Treatment response in children and adolescents with anorexia nervosa: a naturalistic, case-control study.

PURPOSE: Although a few recent articles describe adults with treatment-resistant anorexia nervosa (TR-AN), no study addresses the specific features of subjects not responding to treatment in the developmental age. This study reports on the clinical and psychopathological variables that distinguish children and adolescents who did not respond to treatment (here "TR-AN") from good-outcome controls, in a multidisciplinary hospital treatment setting. METHODS: Naturalistic, case-control study conducted on individuals showing lack of response to treatment and good-outcome controls. TR-AN was defined as two or more incomplete admissions and no complete admissions, consistently with studies in adults. Good-outcome was defined as complete first admission, availability for follow-up visit after 6 months, and maintaining at follow-up a %BMI > 70% in the absence of binging or purging in the preceding 3 months. Psychopathological (Eating Disorders Inventory-3 EDI-3; Beck Depression Inventory-II), clinical, and treatment variables at admission were compared. Significant differences in the univariate analyses were included in an exploratory binary logistic regression. RESULTS: Seventy-six patients (30 TR-AN, 46 good-outcome AN controls) were enrolled (mean age 14.9 ± 1.9 years, F = 94.7%). TR-AN individuals had a higher age at admission and higher EDI-3 Eating Disorder Risk (EDRC) scores, were treated less frequently with a nasogastric tube (NGT), and achieved a lower BMI improvement at discharge than good-outcome controls. A predictive model for TR-AN status was found (X2 = 19.116; Nagelkerke-R2 = 0.478, p < 0.001), and age at admission (OR = 0.460, p = 0.019), EDI-3 EDRC (OR = 0.938, p = 0.043), and NGT (OR = 8.003, p = 0.019) were associated with a TR-AN status. CONCLUSIONS: This is the first report on the psychopathological and clinical characteristics of children and adolescents not responding to treatment. These patients showed higher age and eating disorder scores, and were less frequently fed with NGT than controls. Despite the multiple incomplete admissions of our subjects, the short included follow-up limits the possibility for direct comparisons with adult samples of treatment-resistant patients. Thus, the specific features of children and adolescents with TR-AN should be assessed in longitudinal studies. LEVEL OF EVIDENCE: III, Observational, case-control study.

The Role of the Noradrenergic System in Eating Disorders: A Systematic Review.

Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.

The involvement of the adrenergic system in feeding and eating disorders. A systematic review.

BACKGROUND: Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED). This review aims to synthesise the current evidence on the role of adrenergic dysregulation in the pathogenesis and management of FED. METHODS: A systematic review was conducted in MEDLINE, Cochrane Library, and Clinicaltrials.gov. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was adopted. Preclinical, clinical, and pharmacological studies assessing the adrenergic system in FED were included. RESULTS: Thirty-one out of 1415 recognised studies were included. Preclinically, studies on adrenaline's anorectic impact, receptor subtypes, and effects on hepatic function in rats show that catecholamine anorexia is primarily alpha-adrenergic, whereas beta-adrenergic anorexia can be obtained only after puberty, implying an impact of sexual hormones. Clinically, catecholamine levels may be higher in FED patients than in healthy controls (HC). Individuals with anorexia nervosa (AN) may show higher epinephrine-induced platelet aggregability response than HC. Pharmacological trials suggest that the alpha-2-adrenergic medication clonidine may not lower AN symptoms, but agents regulating the adrenaline-noradrenaline neurotransmission (bupropion, reboxetine, duloxetine, sibutramine) have been found to improve binge eating symptoms. CONCLUSION: Adrenergic dysregulation may be involved in the pathophysiology of FED. More research is needed to comprehend underlying mechanisms and treatment implications.

Psychopathological and Organic Features of Atypical Anorexia Nervosa in Developmental Age: A Systematic Review.

PURPOSE: This study aimed to comprehensively report the epidemiological and clinical features of atypical anorexia nervosa (AAN) in children and adolescents. METHODS: In May 2024, a systematic review was performed using Medline, Cochrane Library, ClinicalTrials.gov, and relevant websites. Following PRISMA guidelines, 234 articles were screened for studies on DSM-5-defined AAN. A standardized checklist-the JBI critical appraisal tool-was adopted in assessing methodology, and 13 retained studies passed the screening and critical appraisal process for the final review. The Newcastle-Ottawa Scale was utilized to assess the risk of bias in cohort and case-control studies, ensuring a comprehensive evaluation of methodological quality. RESULTS: AAN prevalence in young age groups is 2.8%, with a cumulative 2.8% incidence over 8 years. Incidence is 366 per 100,000 person-years, and the average episode duration is 11.6 months, with a 71% remission rate. Diagnostic persistence for AAN is less stable than other restrictive feeding and eating disorders (FEDs). AAN individuals exhibit higher EDE-Q scores, more severe distress, and distinct BMI differences compared to those with anorexia nervosa and controls. The diagnostic transition from the DSM-IV to the DSM-5 shows that AAN patients are predominantly female, slightly older, and with higher weight. CONCLUSIONS: This study yields concrete insights into the features of AAN in the developmental age, highlighting demographic variations, clinical presentations, and treatment outcomes. Recognizing the unique challenges faced by AAN individuals is vital for tailoring effective interventions and improving overall care within the FED spectrum.

Nutritional Assessment of Children and Adolescents with Atypical Anorexia Nervosa: A Preliminary Longitudinal Investigation Using the 24-h Dietary Recall.

BACKGROUND: Atypical Anorexia Nervosa (AAN) is a Feeding and Eating Disorder characterized by fear of gaining weight and body image disturbance, in the absence of significantly low body weight. AAN may present specific clinical and psychopathological features. Nonetheless, the literature lacks data concerning the nutritional characteristics and body composition of children and adolescents with AAN and their variation over time. METHODS: Case series, including 17 children and adolescents with AAN. All the patients were assessed at the first evaluation (T0) with a standardized dietary assessment (24 h Dietary Recall, 24 hDR). Nutritional data were compared with European dietary reference values (DRVs). Body composition parameters (weight, fat mass, fat-free mass) and their changes over time at two (T1) and six (T2) months were collected as well, using a Bioelectrical impedance analysis (Wunder WBA300 with four poles and foot contact; impedance frequency 50 kHz 500 µA; impedance measurement range 200~1000 Ω/0.1 Ω). RESULTS: The included individuals presented eating behaviors oriented towards significantly low daily energy intake (p < 0.001) compared with DRVs set by the European Food Safety Authority (EFSA) (with low carbohydrates and fats), and increased proteins (p < 0.001). A longer latency before observation (illness duration before observation) correlated with a negative change in weight. Body composition parameters were described, with no significant changes across the six-month outpatient assessment. DISCUSSION: This is the first research to systematically assess the body composition and nutritional features of a group of individuals with AAN in the developmental age. Further research should assess the effect of targeted treatment interventions on body composition and nutritional features.

A Male Child with Infantile Epilepsy due to a Mosaic Missense Variant of PCDH19.

Background: Pathogenic variants of PCDH19, located on the X-chromosome (Xq22.1), cause a rare epileptic encephalopathy with speech and development delay, seizures, behavioral and psychiatric problems. The specific underlying pathogenic mechanism is known as "cellular interference" that results in affected heterozygous females, normal hemizygous males and affected mosaic males but its functioning is not yet clear. Objectives: Reporting new cases of affected males is considered useful to a deeper insight. Subject and Method: We present the case of a three-year-old boy with early-onset seizures at 3 months of age, mild cognitive impairment, partial control of seizures with levetiracetam, normal brain imaging. Results: The patient has a mosaic pathogenic variant c.698A>G (p.Asp233Gly) in PCDH19 assessed by Next Generation Sequencing analysis. We have compared his characteristics with the genotypes and phenotypes of 34 PCDH19 mosaic males earlier reported in the literature. Finally, we have summarized today's knowledge about phenotype-genotype correlation and pharmacological response in these patients. Conclusions: Our report confirms that the clinical picture of mosaic affected males, resembling that of females, can show a wide variability in severity of disease and underlines a stringent need to improve therapeutic approaches and to collect data on long-term follow-up.

Early onset anorexia nervosa: Multidisciplinary hospital intervention in a 1-year follow-up study.

BACKGROUND: Early onset anorexia nervosa (EOAN) is a subclassification of AN, defined by an onset before 14 years, and characterized by specific demographic, neuropsychological, and clinical features. The present study aims to provide naturalistic data on a wide sample with EOAN, focusing on psychopathological and nutritional changes occurring in the context of a multidisciplinary hospital intervention, as well as the rate of rehospitalizations during a 1-year follow-up. METHOD: Observational, naturalistic study adopting standardized criteria for EOAN (onset before 14 years). EOAN were compared to adolescent-onset AN (AOAN) patients (onset after 14 years) by demographic, clinical, psycho and treatment variables. Psychopathology was assessed at admission (T0) and discharge (T1) with self-administered psychiatric scales for children and adolescents (SAFA) subtests for Eating Disorders, Anxiety, Depression, Somatic symptoms, and Obsessions. Then, potential differences of T0-T1 changes in psychopathological and nutritional variables were assessed. Finally, rates of re-hospitalizations at 1-year post-discharge follow-up were assessed with Kaplan-Meier analyses. RESULTS: Two-hundred thirty-eight AN individuals (EOAN = 85) were enrolled. When compared to AOAN, EOAN participants were more frequently males (X2 = 5.360, p = .021), more frequently received nasogastric-tube feeding (X2 = 10.313, p = .001), and risperidone (X2 = 19.463, p < .001), obtained a greater T0-T1 improvement in body-mass index percentage (F[1.229] = 15.104, p < .001, η2 = 0.030), with higher 1-year freedom from re-hospitalization (hazard ratio, 0.47; Log-rank: X2 = 4.758, p = .029). CONCLUSION: In this study, describing the broadest EOAN sample available in literature so far, EOAN patients received specific interventions and obtained better outcomes at discharge and follow-up when compared to AOAN. Longitudinal, matched studies are required.

The role of risperidone in the treatment of children and adolescents with anorexia nervosa.

BACKGROUND: Current Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-based research provides limited data on the use of risperidone on children and adolescents with anorexia nervosa (AN) mainly in small-sample/case report studies. AIM: To report the use of risperidone in a group of children and adolescents with feeding and eating disorders, specifically with AN. METHODS: Observational, naturalistic study. Psychopathology was assessed with Eating Disorders Inventory-3, Beck's Depression Inventory-II, and Symptom Checklist-90-R. Data were reported for the whole sample, for patients treated with risperidone, and finally compared between patients with AN treated with risperidone and those receiving no atypical antipsychotics. Potential differences in admission-discharge changes in body mass index (BMI) and psychopathology were assessed with analyses of covariance corrected for baseline measures. Kaplan-Meier analyses were conducted to assess retention rates of risperidone (at 3 months and 1 year) and rates of rehospitalization on 1-year follow-up. RESULTS: The study enrolled 120 patients with AN (42 treated with risperidone). Risperidone was used for 116.7 (±122.8) days (total exposure = 3979 days) and well-tolerated (nausea, asthenia in one case). No significantly different admission-discharge improvements for BMI or psychopathology were documented for patients treated with risperidone. Risperidone showed a 3-month retention rate of 50.0% (1 year: 9.5%) and was discontinued mainly for the resolution of target symptoms. Cumulative freedom from rehospitalization at 12 months was comparable for treated and untreated patients (hazard ratio = 1.088; Log-rank p = 0.908). CONCLUSIONS: This study reports real-life evidence of the use of risperidone in AN children and adolescents in the widest described sample so far. Longitudinal research should assess long-term prognostic factors and tolerability.