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

SUNCT/SUNA in pediatric age: A review of pathophysiology and therapeutic options

The International Classification of Headache Disorders, 3rd edition (ICHD3) defines Short-lasting Unilateral Neuralgiform Headache Attacks (SUNHA) as attacks of moderate or severe, strictly unilateral head pain lasting from seconds to minutes, occurring at least once a day and usually associated with prominent lacrimation and redness of the ipsilateral eye. Two subtypes of SUNHA are identified: Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) and Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms (SUNA). These pathologies are infrequent in children and difficult to diagnose. The authors reviewed the existing literature on SUNCT and SUNA, especially in the developmental age, which describes the pathophysiology in detail and focuses on the therapeutic options available to date. SUNHA-type headaches must be considered on the one hand, for the possibility of the onset of forms secondary to underlying pathologies even of a neoplastic nature, and on the other hand, for the negative impact they can have on an individual’s quality of life, particularly in young patients. Until now, published cases suggest that no chronic variants occur in childhood and adolescents. In light of this evidence, the authors offer a review that may serve as a source to be drawn upon in the implementation of suitable treatments in children and adolescents suffering from these headaches, focusing on therapies that are non-invasive and as risk-free as possible for pediatric patients

Adjunctive clotiapine for the management of delusions in two adolescents with anorexia nervosa

Clotiapine is an atypical antipsychotic indicated for the management of a series of acute psychotic disorders. The current literature lacks evidence concerning the tolerability and clinical use of this drug in the management of individuals with anorexia nervosa (AN). In this study, we report two cases of adolescents with AN, treated with clotiapine. The reason for the administration of clotiapine was, for both patients, the manifestation of bizarre delusions concerning food and calories. Patient 1 presented a presyncope after the first dose of clotiapine, and treatment was rapidly discontinued. Patient 2 was treated with clotiapine for 9 months; doses were titrated from 20 mg/day to 70 mg/day, with an improvement in the reported delusions, which also enhanced compliance with psychological and nutritional interventions. EKG, QTc, white blood count, and red blood count were not relevantly influenced by the introduction of clotiapine in either patient. No extrapyramidal effect was documented. These reports stress the need for further studies assessing the tolerability and potential effect of clotiapine in treating adolescents with AN and delusional symptomatology

Expanding the neurological phenotype of ring chromosome 10 syndrome: A case report and review of the literature

Ring chromosome 10 [r(10)] syndrome is a rare genetic condition, currently described in the medical literature in a small number of case report studies. Typical clinical features include microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations. We report a novel case of r(10) syndrome and review the neurological and neuro-radiological phenotypes of the previously described cases. Our patient, a 3 year old Italian girl, represents the 20th case of r(10) syndrome described to date. Intellectual disability/developmental delay (ID/DD), microcephaly, strabismus, hypotonia, stereotyped/aggressive behaviors and elec-troencephalographic abnormalities were identified in our patient, and in a series of previous cases. A brain MRI disclosed a complex malformation involving both the vermis and cerebellar hemispheres; in the literature, posterior cranial fossa abnormalities were documented by CT scan in another case. Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome. Although r(10) syndrome represents an extremely rare condition, with a clinical characterization limited to case reports, the recurrence of specific neurological and neuroradiological features suggests the need for specific genotype-phenotype studies

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

Autism spectrum disorder and anorexia nervosa: an Italian prospective study

Background: Potential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study investigates possible associations among the psychopathology of Eating Disorders (EDs), ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD. Methods: Prospective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering the ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Correlations were adjusted for BMI, Obsessive Compulsive Disorder (OCD) comorbidity and concurrent antipsychotic treatments. Results: An ASD diagnosis was possible in 22% of patients. Significant correlations were documented between ASD traits and ED psychopathology: AQ total-Interpersonal problems (IPC) (p = 0.041); AQ total-Global psychological maladjustment (GMPC) (p = 0.027); AQ social skills-Ineffectiveness (IC) (p = 0.018); AQ social skills-IPC (p = 0.019); AQ social skills-Affective problems (APC) (p = 0.025); AQ social skills-GMPC (p = 0.007); AQ attention switching-IPC (p = 0.020); ADOS-2 imagination-IC (p = 0.035). These correlations were independent of BMI, OCD and antipsychotic treatments. Conclusions: ASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 4 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI

Electronically preresonant stimulated Raman scattering microscopy in the visible

We report an experimental scheme for stimulated Raman scattering (SRS) microscopy with excitation in the visible spectral region. This allows electronically preresonant (epr) SRS microscopy of a broad range of chromophores with sensitivities as low as 1 μM. Our experiment is based on two synchronously near-infrared pumped optical parametric oscillators (OPO). One of the outputs is modulated at a fourth of the repetition rate with a novel broadband electro-optical modulator. Using a combination of spectral focusing and tuning of the OPO, we show the recording of epr-SRS spectra over the whole range of molecular vibrations at a speed up to 20 times faster than classical wavelength tuning. The imaging capabilities of this setup are demonstrated with material scientific and cellular samples

Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation

A new series of eight multifunctional thalidomide–donepezil hybrids were synthesized based on the multi target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the N-benzylpiperidine pharmacophore of donepezil and the isoindoline 1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC50 value of 3.15 μM, which was predicted by docking studies as interacting with the enzyme in the same orientation observed in the AChE–donepezil complex and a similar profile of interaction. Additionally, compound 3g significantly decreased iNOS and IL-1β levels by 43% and 39%, respectively, after 24 h of incubation with lipopolysaccharide. In vivo data confirmed the ability of 3g to prevent locomotor impairment and changes in feeding behavior elicited by lipopolysaccharide. Moreover, the PAMPA assay evidenced adequate blood–brain barrier and gastrointestinal tract permeabilities with an Fa value of 69.8%. Altogether, these biological data suggest that compound 3g can treat the inflammatory process and oxidative stress resulting from the overexpression of iNOS and therefore the increase in reactive nitrogen species, and regulate the release of pro-inflammatory cytokines such as IL-1β. In this regard, compound PQM-189 (3g) was revealed to be a promising neuroprotective and anti-neuroinflammatory agent with an innovative thalidomide–donepezil-based hybrid molecular architectur

The pandemic within the pandemic: the surge of neuropsychological disorders in Italian children during the COVID-19 era

Background: Quarantine and isolation measures during COVID-19 pandemic may have caused additional stress and challenged the mental health of the youth. Aim of the study is to investigate the COVID-19 pandemic impact on neuropsychological disorders (NPD) of Italian children and adolescents to provide general pediatric recommendations. Material and methods: A retrospective multicenter observational study was planned by the Italian Pediatric Society (SIP) to explore the impact of COVID-19 on the access of children to pediatric Emergency Departments (pED) for the evaluation of neuropsychological symptoms, collecting the classification codes of diagnoses between March 1, 2019 and March 2, 2021. The period study was split into two sub-periods: a pre COVID-19 period (from March 1 2019 to March 1, 2020) and a COVID-19 period (from March 2, 2020 to March 2, 2021). As additional information, data on NPD hospitalizations in any pediatric department of the involved centers were recorded. Results: During the study period, a total of 533,318 children were admitted to the pED involved in the study. Despite a 48.2% decline of pED admissions, there was a significant increase (83.1%) in patient admissions for NPD. The most frequent NPD conditions which increased during the COVID-19 pandemic were suicidal ideation (+ 147%), depression (+ 115%), eating disorder (+ 78.4%), and psychosis (+ 17.2%). During the pandemic period, a 39.5% increase in NPD hospitalizations was observed as well. The NPD disorders that mostly required hospitalizations were suicidal ideation (+ 134%), depression (+ 41.4%), eating disorder (+ 31.4%), and drug abuse (+ 26.7%). COVID-19 pandemic had a major impact on children's health, mainly on their NPD development. Neuropsychological assessment should be required at the primary level, in the pediatrician's office, to facilitate early capture of the sign of impairment and provide an adequate treatment. Conclusion: SIP underlines the psychological consequences of COVID 19 pandemic on the youngest and recommends an early identification of NPD in the pediatric population to avoid other serious consequences for children's physical and mental health

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