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.

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.

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.

Food and Development: Children and Adolescents with Neurodevelopmental and Comorbid Eating Disorders-A Case Series.

The impact of psychiatric comorbidities in the diagnosis and treatment of feeding and eating disorders (FEDs) represents an emerging research topic. The current literature, nonetheless, lacks studies investigating the developmental paths of individuals with FEDs and comorbid neurodevelopmental disorders (NDDs). Here, we report 11 cases of children and adolescents with comorbid FEDs and NDDs, as assessed along the neuropsychological, psychopathological, and nutritional developmental pathways. The onset of FED-related psychopathology was preceded, sometimes undiagnosed, by altered neurodevelopmental features leading to specific NDD diagnoses (autism spectrum disorder-ASD; attention-deficit/hyperactivity disorder-ADHD; specific learning disorder-SLD). NDDs appeared to influence the diagnoses and treatments of FEDs, frequently with an impact on socio-relational and emotional premorbid features, and on the possibility to receive and attend FED-targeted treatments. Further studies should longitudinally contribute to assessing the experiences of care and neurodevelopmental pathways of children with FEDs and specific NDD comorbidities.

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.

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.

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.

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.

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.

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.

Antipsychotics in the Treatment of Children and Adolescents with Anorexia Nervosa: A Systematic Review.

Evidence about the use of pharmacologic agents in the treatment of Anorexia Nervosa (AN) is lacking, especially in childhood and adolescence. A systematic scoping review was conducted to outline current literature evidence about the use of antipsychotics in this population. A total of 499 studies were identified with the initial search, and 28 of these studies were selected regarding the use of olanzapine (n = 13), risperidone (n = 4), aripiprazole (n = 3), chlorpromazine (n = 3), pimozide (n = 1) clotiapine (n = 1) and multiple antipsychotics (n = 3) in these patients. Overall, major side effects were reported infrequently; improvements in psychopathology and weight measures have been suggested in the majority of the considered studies. Nonetheless, the lack of RCT or good-quality studies strongly limits the generalizability of results in clinical practice.

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.

The use of TikTok among children and adolescents with Eating Disorders: experience in a third-level public Italian center during the SARS-CoV-2 pandemic.

BACKGROUND: Recent research has documented the potential associations existing between the use of social media (SM) and the occurrence/development and treatment of Eating Disorders (ED). However, the literature directly addressing the use of SM TikTok among children and adolescents with ED is still scarce. METHODS: In January-February 2021, during the second Italian national lockdown due to the SARS-CoV-2 pandemic, an anonymous paper survey was conducted in an Italian third-level center for ED in childhood and adolescence. Demographics, frequency of use of TikTok, frequently viewed topics and hashtags, experienced body-shaming, as well as the use of TikTok (active search, use of proposed contents) and perceived influences of this SM on eating attitudes and self-esteem were assessed. Groups of patients with different perceived SM-induced effects were compared to determine the frequency of their interaction with 3 specific contents (diet, Pro-Anorexia Nervosa (pro-Ana) and pro-ED recovery). RESULTS: Seventy-eight patients (93.6% females, mean age 14.5 ± 2.1 years) were enrolled in the study. For 62.8%, TikTok represented the main SM, used for 1.4 ± 1.0 h/day, with diet (21.8%) as the most frequently used topic category. Pro-Ana and pro-ED recovery contents ("#foryou" and "#edrecovery" as the most frequent, respectively) were both actively searched by patients and proposed by the SM in a significant number of cases. For 59.0%, using TikTok reduced self-esteem, while 26.9% reported TikTok-related significant changes in their daily lives, and 3.8% reported experiences of body-shaming. Patients describing a negative effect of TikTok on their self-esteem more frequently searched and browsed "diet" (p = 0.007) and pro-ED recovery (p = 0.007) contents. Positive qualitative feedback on the SM was also reported. CONCLUSIONS: This study documents the use of the SM TikTok among children and adolescents with ED. Individuals with a perceived negative effect of this SM on their self-esteem may show greater interaction with specific content. Further studies are needed to investigate the psychopathological factors influencing the relationship between ED and the use of SM.

Children with Prepubertal Anorexia Nervosa: assessing the sex hormone profile and prognostic factors for inpatient treatment outcomes.

BACKGROUND: Even though Anorexia Nervosa (AN) is an emerging research topic, scarce literature data are available on children with prepubertal AN. To date, no specific study has assessed the potential prognostic factors on treatment outcomes in this population. METHODS: Observational, retrospective study of 39 children (12.5±1.8 years) hospitalized for AN, with primary amenorrhea and absence of pubertal development at clinical examination. Sexual hormonal profile: plasma levels luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P4), and prolactin (PRL) were assessed at admission. Clinical (age, duration of illness, comorbidity, admission body-mass index - BMI), treatment (psychopharmacological therapies) and outcome (BMI improvement, length of hospital stay - LOS) variables were assessed. Multiple linear regressions were conducted to assess potential predictors of outcomes. RESULTS: A predictive model of BMI improvement (F(4, 32)=8.713; Adjusted R2=0.491; p<0.001) was documented, with longer LOS (B=0.010; p<0.001), lower plasma levels of E2 (B=-0.043; p=0.002) and lower plasma levels of LH (B=-0.292, p=0.043) predicting a greater BMI improvement. A predictive model of LOS (F(2, 38)=9.527; Adjusted R2=0.310; p<0.001) was documented as well, with younger age (B=17.835; p<0.001), and reduced BMI improvement (B=22.656; p=0.012) predicting a shorter LOS. No predictive value of comorbidity, FSH, P4 or PRL was found. CONCLUSIONS: This is the first study to investigate the prognostic value of sex hormones on the treatment of children with prepubertal AN. Low E2, LH, and age, but not FSH, P4 or PRL, were associated with better outcomes. These data should be investigated in wider populations and controlled studies.

Lithium treatment in children and adolescents with anorexia nervosa: clinical use, side effects and tolerability.

PURPOSE: Current guidelines, due to potential toxicity and lack of clinical evidence, do not recommend the use of lithium in the treatment of Anorexia Nervosa (AN). Scarce evidence is available on the use, side effects, and tolerability of this drug in children and adolescents with AN, a population characterized by specific clinical, metabolic, and hydro-electrolytic balance features. Here we report a case series of children and adolescents hospitalized for AN and treated with lithium. METHODS: Case series reporting the use of lithium in 7 female young patients with AN. Reasons for introduction, dosages, formulation, plas-ma levels, adverse drug reactions (ADR) and modifi-cations of electrocardiogram (EKG) and plasma levels of glucose, cholesterol, creatinine, urea, sodium, and thyroid-stimulating hormone (TSH) were assessed. Re-sults. Reasons for the introduction of lithium included unstable mood, insufficient compliance with nutri-tional programs, and psychomotor agitation. In all of the patients an improvement on target symptoms was observed. Lithium was started at 171.4 (+/-56.7) mg/day, up to 600.0 (+/-173.2) mg/day. The most frequent scheme was three times daily. The mean plasmatic concentration was 0.6 (+/-0.3) mmol/L at one month. One pa-tient experienced polyuria, polydipsia and dry mouth, and another showed increased creatinine kinase. No major modifications of EKG, glucose, cholesterol, cre-atinine, urea, sodium emerged. CONCLUSIONS: In this sample of children and adolescents hospitalized for AN, lithium was administered to improve psychiatric symptoms impairing compliance. All the patients experienced an improvement on these symptoms after being admin-istered lithium. ADR were reported in 2 cases. These data should be investigated in wider populations and controlled studies.

Epilepsy Course and Developmental Trajectories in STXBP1-DEE.

Background and Objectives: Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1-DEE and dissect the relationship between neurodevelopment and epilepsy. Methods: Retrospective standardized clinical data were collected through international collaboration. A composite neurodevelopmental score system compared the developmental trajectories in STXBP1-DEE. Results: Forty-eight patients with de novo STXBP1 variants and a history of epilepsy were included (age range at the time of the study: 10 months to 35 years, mean 8.5 years). At the time of inclusion, 65% of individuals (31/48) had active epilepsy, whereas 35% (17/48) were seizure free, and 76% of those (13/17) achieved remission within the first year of life. Twenty-two individuals (46%) showed signs of developmental impairment and/or neurologic abnormalities before epilepsy onset. Age at seizure onset correlated with severity of developmental outcome and the developmental milestones achieved, with a later seizure onset associated with better developmental outcome. In contrast, age at seizure remission and epilepsy duration did not affect neurodevelopmental outcomes. Overall, we did not observe a clear genotype-phenotype correlation, but monozygotic twins with de novo STXBP1 variant showed similar phenotype and parallel disease course. Discussion: The disease course in STXBP1-DEE presents with 2 main trajectories, with either early seizure remission or drug-resistant epilepsy, and a range of neurodevelopmental outcomes from mild to profound intellectual disability. Age at seizure onset is the only epilepsy-related feature associated with neurodevelopment outcome. These findings can inform future dedicated natural history studies and trial design.

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.

Specific Learning Disorders and Eating Disorders: an Italian retrospective study.

BACKGROUND: Although Anorexia Nervosa (AN) patients show dysfunctional behaviour in information processing, visual and verbal memory performance, and different cognitive fields, regardless of their BMI, the literature on the correlations between Eating Disorders (ED) and Neurodevelopmental Disorders (NDD) does not provide conclusive data. Rather than a consequence of the mental disorder, cognitive dysfunctions may be a risk factor for AN. METHODS: Our retrospective study investigates the prevalence of Specific Learning Disorder (SLD) among patients with ED. We considered 262 patients being treated at the Emilia Romagna Feeding and Eating Disorders Outpatient Service in Bologna, Italy. We compared the results with the Italian reference values, according to the most recent data provided by the Italian Ministry of Education. RESULTS: We found that 25 patients out of 262 (9.54%) presented a comorbid diagnosis of SLD. This SLD prevalence is higher than the Italian reference values (4.9% in the school year 2018/19, p < 0.001). Comorbidity with SLD was significantly more frequent in males. A diagnosis of SLD was not associated with a higher frequency of any specific ED diagnosis or with psychiatric comorbidity in general. Positive family history for SLD was not significantly associated with either a positive family history for ED or a diagnosis of SLD. CONCLUSIONS: This is the first Italian study to investigate the prevalence of SLD in ED patients during childhood and adolescence. Our data support previous research documenting that neuropsychological deficit could lead to the development of ED.

Low-Dose Olanzapine in the Treatment of Adolescents with Anorexia Nervosa: An Observational Naturalistic Case-Control Study.

Background: Although recent articles have investigated the use of low-dose olanzapine in different psychiatric conditions, only one study so far has assessed this treatment in 13 girls with anorexia nervosa (AN). Methods: Observational naturalistic case-control study aimed at reporting the use and tolerability of low-dose olanzapine in the context of a multidisciplinary hospital intervention for adolescents with AN. Three groups with AN were compared: group 1 was treated with low-dose olanzapine (≤5 mg/day), group 2 with full-dose olanzapine (>5 mg/day), and group 3 (control group) was treated without antipsychotics. Psychopathology was assessed at admission (T0) and discharge (T1) with Eating Disorders Inventory-3 Eating Disorders Risk, Body Uneasiness Test Global Severity Index (BUT-GSI), Beck's Depression Inventory-II (BDI-II), and Self-administered Psychiatric Scales for Children and Adolescents, Depression subtest (SAFA-D). Possible differences among the three groups, concerning clinical and treatment variables, were screened. Then, potential differences of T0-T1 modifications in psychopathological variables among the three treatment groups were assessed with analyses of covariance, corrected for baseline psychopathology and potential confounders, including possible concurrent antidepressants. Results: A total of 118 patients were enrolled (F = 94.1%; mean age = 15.4 ± 1.7 years), including 52 controls, 37 treated with low-dose olanzapine, and 29 with full-dose olanzapine. Low-dose olanzapine was well tolerated and used for a mean of 132.1 (±98.6) days, starting with a dosage of 3.4 (±1.2) mg/day and increasing to a maximum dose of 4.4 (±1.1) mg/day. The multidisciplinary intervention resulted in an improvement of BUT-GSI (p < 0.001), BDI-II (p < 0.001), and SAFA-D (p < 0.001) for the entire sample. Individuals treated with full-dose olanzapine experienced a significantly lower improvement in depressive measures: BDI-II (F[2,61] = 12.653, p < 0.001, η2 = 0.269) and SAFA-D (F[2,57] = 7.413, p = 0.001, η2 = 0.170), than the other groups. Discussion: This naturalistic controlled study expands the existing evidence on the use and tolerability of low-dose olanzapine in adolescents with AN. These results should be assessed in wider and prospective samples.

Anorexia nervosa among first- and second-generation immigrant children and adolescents in Italy: treatment and clinical outcomes.

PURPOSE: Cultural and environmental factors have frequently been implicated in the pathogenesis of Eating Disorders (ED). Although ED have been considered as "Western culture-bound syndromes", increasing rates of ED among non-Western groups are being documented. The present study aims to investigate treatment and clinical outcomes among first-generation immigrant children and adolescents (FGI) (patients born abroad) and second-generation immigrant youth (SGI, patients born in Italy) with Anorexia Nervosa (AN). METHODS: The study retrospectively compares treatment, hospitalizations, traumatic past events, clinical features, and treatment outcome (improvement in percentual body-mass index - %BMI) between FGI and SGI young patients with AN (10-18 years). Correlations were adjusted for age and severity (%BMI) at presentation. Treatments and outcomes were investigated at the baseline (T0), 2 weeks (T1), one month (T2), 3 months (T3), 6 months (T4), and 12 months (T5). RESULTS: Thirty-six patients (50% FGI) were enrolled. At T1 (F(1.26)=6.335, p=0.018), and at T2 (F(1.30)=18.752, p<0.001) FGI presented a significantly higher %BMI improvement than SGI. FGI required significantly less (OR=0.379, p=0.017), and shorter (F(1.32)=5.827, p=0.022) hospitalizations, when compared with SGI. CONCLUSIONS: When compared to SGI, FGI with AN required fewer and shorter hospitalizations and had a better early-treatment weight outcome. Larger nationwide studies should investigate the need for and access to treatment of immigrant populations with AN.