Adolescent Mental Health: A Focus on Psychiatric Counseling from the Emergency Room of an Italian University Hospital in the Five Years from 2019 to 2023.

Recent studies have revealed increasingly worse and more complex mental health conditions in young people, which is reflected in a growing trend in emergency room (ER) visits for acute psychopathological symptoms (APSs). This phenomenon has become exacerbated in recent decades, with a peak in the post-pandemic period. To better characterize the phenomenon, we investigated the change in the rate and type of ER counseling requests provided at the Child Neuropsychiatry Unit of the University Hospital of Bari, Italy over the period between 2019 and 2023 for subjects younger than 18 years old. For this purpose, we retrospectively analyzed a total number of 1073 urgent consultation reports retrieved through the reporting computerized operating system of our hospital. The distribution of the counseling requests provided for APSs and, among these, the distribution of the numbers of APSs and of the male: female ratio were significantly different over the years, with an increasing linear trend identified for APSs (p = 3.095 × 10-7), the average number of APSs (p = 3.598 × 10-7), and female gender prevalence (p = 0.03908), as well as for the patients with a history of psychotropic drug assumption (p = 0.0006319). A significant change in the number of urgent counseling requests received for eating disorders (p = 0.0007408), depression (p = 7.92 × 10-8), somatization (p = 4.03 × 10-6), self-harm (SA) (p = 1.358 × 10-6), and non-suicidal self-injury (NSSI) (p = 8.965 × 10-6) was found, with a significant increasing trend for anxiety (p = 0.0444), depression (p = 8.06 × 10-6), somatization (p = 0.004616), SA (p = 3.998 × 10-8), and NSSI (p = 5.074 × 10-7). The findings of our study support the hypothesis of an alarming progressive worsening of the mental health of children and adolescents, with an overlapping effect of the pandemic exacerbating the process.

The management of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD): an update of the literature.

INTRODUCTION: Sleep disorders represent an important comorbidity in individuals with ADHD. While the links between ADHD and sleep disturbances have been extensively investigated, research on the management of sleep disorders in individuals with ADHD is relatively limited, albeit expanding. AREAS COVERED: The authors searched PubMed, Medline, PsycInfo, Embase+Embase Classic, Web of Sciences databases, and clinicaltrials.gov up to 4 January 2024, for randomized controlled trials (RCTs) of any intervention for sleep disorders associated with ADHD. They retained 16 RCTs (eight on pharmacological and eight on non-pharmacological interventions), supporting behavioral intervention and melatonin, and nine ongoing RCTs registered on clinicaltrials.gov. EXPERT OPINION: The pool of RCTs testing interventions for sleep disorders in individuals with ADHD is expanding. However, to inform clinical guidelines, there is a need for additional research in several areas, including 1) RCTs based on a precise phenotyping of sleep disorders; 2) pragmatic RCTs recruiting neurodevelopmental populations representative of those seen in clinical services; 3) trials testing alternative interventions (e.g. suvorexant or light therapy) or ways to deliver them (e.g. online); 4) sequential and longer-term RCTs; 5) studies testing the impact of sleep interventions on outcomes other than sleep; 6) and implementation of advanced evidence synthesis and precision medicine approaches.

A state-of-the-art overview of candidate diagnostic biomarkers for Attention-deficit/hyperactivity disorder (ADHD).

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental conditions and is highly heterogeneous in terms of symptom profile, associated cognitive deficits, comorbidities, and outcomes. Heterogeneity may also affect the ability to recognize and diagnose this condition. The diagnosis of ADHD is primarily clinical but there are increasing research efforts aiming at identifying biomarkers that can aid the diagnosis. AREAS COVERED: We first discuss the definition of biomarkers and the necessary research steps from discovery to implementation. We then provide a broad overview of research studies on candidate diagnostic biomarkers in ADHD encompassing genetic/epigenetic, biochemical, neuroimaging, neurophysiological and neuropsychological techniques. Finally, we critically appraise current limitations in the field and suggest possible ways forward. EXPERT OPINION: Despite the large number of studies and variety of techniques used, no promising biomarkers have been identified so far. Clinical and biological heterogeneity as well as methodological limitations, including small sample size, lack of standardization, confounding factors, and poor replicability, have hampered progress in the field. Going forward, increased international collaborative efforts are warranted to support larger and more robustly designed studies, develop multimodal datasets to combine biomarkers and improve diagnostic accuracy, and ensure reproducibility and meaningful clinical translation.

Correlations between Sleep Features and Iron Status in Children with Neurodevelopmental Disorders: A Cross-Sectional Study.

A high prevalence of sleep disturbances has been reported in children with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). The etiology of sleep disorders in these children is heterogeneous and, recently, iron deficiency has received increasing attention. This study aims to investigate sleep features in children with NDDs and to explore a possible correlation between serum iron status biomarkers and qualitative features of sleep. We included 4- to 12-year-old children with a diagnosis of ASD, ADHD, or ID and assessed their sleep features through the children's sleep habits questionnaire (CSHQ). Venous blood samples were collected to investigate ferritin, transferrin, and iron levels. The mean CSHQ total score exceeds the cut-off in all groups of children. In the ASD group, the Parasomnias subscale negatively correlated with serum ferritin levels (Rho = 0.354; p = 0.029). Our findings may suggest the existence of an association between iron status, sleep quality, and neurodevelopmental processes. In clinical practice, sleep assessment should be included in the routine assessment for patients with NDDs. Furthermore, a routine assessment of iron status biomarkers should be recommended for children with NDDs who have sleep disturbances.

Social Introversion Personality Trait as Predictor of Internalizing Symptoms in Female Adolescents with Gender Dysphoria.

The personality trait of social introversion refers to the individual inclination toward the inner/outer world. Moreover, adolescents who experience Gender Dysphoria (GD) can be involved in relationship conflicts with family, peers, and friends and experience stigmatization and rejection from society. This leads higher distress in females which are more sensitive to this kind of feelings. This leads in them frequently developing a negative sense of well-being and low self-esteem which increases their risk of internalizing symptoms. So, the aims of this study were: (1) to investigate the presence of significant differences in Social Introversion (SI) dimensions between an assigned-female at birth (AFAB) GD group and a cisgender female group both diagnosed with a depressive disorder, (2) to verify whether the two clinical groups may be characterized by different profiles of internalizing symptoms, (3) to investigate if the SI dimensions could promote the internalizing symptomatology. Our results confirmed the presence of significantly higher score in GD sample for MMPI-SI scale and subscales and showed no significant difference in depressive profiles. Lastly, SI could promote internalizing symptomatology in AFAB underlying a link between SI and depression in this condition which should be further investigated.

Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study.

Autism spectrum disorder (ASD) is one of the most common neurodevelopment disorders, characterized by a multifactorial etiology based on the interaction of genetic and environmental factors. Recent evidence supports the neurobiological hypothesis based on neuroinflammation theory. To date, there are no sufficiently validated diagnostic and prognostic biomarkers for ASD. Therefore, we decided to investigate the potential diagnostic role for ASD of two biomarkers well known for other neurological inflammatory conditions: the glial fibrillary acidic protein (GFAP) and the neurofilament (Nfl). Nfl and GFAP serum levels were analyzed using SiMoA technology in a group of ASD patients and in a healthy control group (CTRS), age- and gender-matched. Then we investigated the distribution, frequency, and correlation between serum Nfl and GFAP levels and clinical data among the ASD group. The comparison of Nfl and GFAP serum levels between ASD children and the control group showed a mean value of these two markers significantly higher in the ASD group (sNfL mean value ASD pt 6.86 pg/mL median value ASD pt 5.7 pg/mL; mean value CTRS 3.55 pg/mL; median value CTRS 3.1 pg; GFAP mean value ASD pt 205.7 pg/mL median value ASD pt 155.4 pg/mL; mean value CTRS 77.12 pg/mL; median value CTRS 63.94 pg/mL). Interestingly, we also found a statistically significant positive correlation between GFAP levels and hyperactivity symptoms (p-value <0.001). Further investigations using larger groups are necessary to confirm our data and to verify in more depth the potential correlation between these biomarkers and ASD clinical features, such as the severity of the core symptoms, the presence of associated symptoms, and/or the evaluation of a therapeutic intervention. However, these data not only might shed a light on the neurobiology of ASD, supporting the neuroinflammation and neurodegeneration hypothesis, but they also might support the use of these biomarkers in the early diagnosis of ASD, to longitudinally monitor the disease activity, and even more as future prognostic biomarkers.

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Association between feeding/mealtime behavior problems and internalizing/externalizing problems in autism spectrum disorder, other neurodevelopmental disorders and typically developing children.

BACKGROUND: The aim of current study was to examine the nature and prevalence of feeding problems and mealtime behavior problems in children with autism spectrum disorder (ASD) comparing to children with other neurodevelopmental disorders (NNDs) and TD children. We also investigated the impact of intelligence quotient (IQ) and/or emotional and behavioral problems on feeding and mealtime behavior problems. METHODS: Participants completed the following tests: Social Communication Questionnaire (SCQ), Child Behavior Checklist (CBCL), Brief Autism Mealtime Behavior Inventory (BAMBI) and Behavioral Pediatric Feeding Assessment Scale (BPFAS). RESULTS: Children with ASD showed more feeding and mealtime behavior problems including food refusal (P<0.001, P<0.001) and limited variety of foods (P=0.014; P=0.018) compared with NDDs and TD children. ASD group showed more problems in mealtime behavior (P=0.034) and parent behaviors (P=0.028) compared to TD group. Internalizing (P=0.003) and externalizing (P=0.008) problems were positively related to parent frustration during mealtime in ASD group. CONCLUSIONS: These results suggest that routine screening for feeding and mealtime behavior problems among children with ASD is necessary to prevent dietary inadequacies that may be associated with eating habits.

Implication of COVID-19 Pandemic on Adolescent Mental Health: An Analysis of the Psychiatric Counseling from the Emergency Room of an Italian University Hospital in the Years 2019-2021.

INTRODUCTION: Although the COVID-19 pandemic had profound consequences on youths' mental health, few data are available about its longitudinal implications. METHOD: In this study, from 655 counseling requests by the Emergency Room (ER) of the University Hospital of Bari, we retrospectively examined 380 requests for psychiatric counseling of pediatric subjects, during the pre-pandemic, the first pandemic, and the second pandemic wave of COVID-19. RESULTS: We found a significant upward trend between 2019 and 2021 for the counseling requests for acute psychopathological symptoms (p = 1.469 × 10-5), patients in adolescent age (p = 0.022), females (p = 0.004), and those taking psychotropic medications (p = 2.28 × 10-5). Moreover, a significant difference in the proportions of depression (p = 0.003), post traumatic (p = 0.047), somatic (p = 0.007) and psychotic symptoms (p = 0.048), and self-injuring behaviors (p = 0.044) was observed. The proportion of counseling for psychotic symptoms (p = 0.014) and self-injuring behaviors (p = 0.035) also showed an increasing trend over time, with self-harming behaviors becoming more severe and diversified in modalities. DISCUSSION: The pandemic's persistence over time may have had an impact on youth's psychopathology, influencing the frequency, type, and complexity of mental health problems; as a result, it is vital to implement timely integrated interventions and find strategies to prevent self-harm, in particular with the identification of vulnerable categories of patients.

Associations of High-Sensitivity C-Reactive Protein and Interleukin-6 with Depression in a Sample of Italian Adolescents During COVID-19 Pandemic.

Introduction: Many studies highlighted the role of inflammation in the pathogenesis of depression, although not for every patient nor for every symptom. It is widely shared that stressors can increase inflammation and lead to depressive symptoms. Little is known about the symptom-specificity of the inflammation-depression link in adolescence, which we aimed to explore. The single symptom analysis is a core feature of the recent network approach to depression, supposing that psychiatric disorders consist of co-occurring symptoms and their tendency to cause each other. Patients and Methods: We recruited 52 adolescents diagnosed with a Depressive Disorder during the COVID-19 stressful period. We used regression analysis to measure associations between high sensitivity C-Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) and depressive symptoms assessed by the Children's Depression Inventory 2 (CDI 2). For the study of symptom specificity, we selected 13 items from the CDI 2 Self Report corresponding with the DSM-5 diagnostic criteria for Major Depressive Disorder and we coded them as dichotomous variables to perform a regression analysis. Results: We found that a higher CDI 2-Parent Version total score was significantly predicted by higher hs-CRP (coefficient 3.393; p 0.0128) and IL-6 (coefficient 3.128; p 0.0398). The endorsement of the symptom self-hatred, measuring the DSM-5 symptom "feelings of worthlessness", was significantly predicted by hs-CRP (OR 10.97; 95% CI 1.29-93.08; p 0.0282). Conclusion: A novel symptom-specificity emerged, with hs-CRP significantly predicting the endorsement of the symptom self-hatred, recognized as a core feature of adolescent depression, following the network theory. We considered it a possible phenotypic expression of one depression endophenotype previously causally linked to inflammation. Due to the limited sample size, these preliminary findings require confirmation with future research focusing on the relationship between inflammation and self-hatred and other central nodes of the depression network, representing an opportunity for targeting interventions on crucial symptoms.

Expectations and Concerns about the Use of Telemedicine for Autism Spectrum Disorder: A Cross-Sectional Survey of Parents and Healthcare Professionals.

Telemedicine has recently been used for diagnosis and interventions inpatients with autism spectrum disorder (ASD), traditionally performed in-person, but little attention has been paid to user expectations prior to its use. The aim of this study is to compare the expectations and concerns of 50 healthcare professionals and 45 parents of children with ASD regarding the use of telemedicine for diagnostic or treatment purposes. Parents have higher expectations for the use of telemedicine as an alternative (p = 0.0223) and supplement (p = 0.0061) to in-person diagnosis of ASD, as well as a supplement to traditional intervention (p ≤ 0.0001). In addition, while they also have greater hope for improvement in family routines (p = 0.0034) and parenting skills in child management (p = 0.0147), they express greater concern about the need for active parental involvement/supervision during telemedicine services (p = 0.015) and changes in the behaviour of the child with ASD during telemedicine services (p = 0.049). On the other hand, healthcare professionals are more concerned about barriers such as lack of devices (p = 0.000), unfamiliarity with the technology (p = 0.000), poor quality of internet connection (p = 0.006), and severity of ASD (p = 0.000). To achieve promising healthcare for ASD patients, the telemedicine service should try to meet the needs and preferences of both healthcare professionals and parents, as well as identify and, if possible, reduce perceived barriers.

Body Emotional Investment and Emotion Dysregulation in a Sample of Adolescents with Gender Dysphoria Seeking Sex Reassignment.

Adolescents with gender dysphoria (GD) often have internalizing symptoms, but the relationship with affective bodily investment and emotion dysregulation is actually under-investigated. The aims of this study are: (1) the comparison of Self-Administrated Psychiatric Scales for Children and Adolescents' (SAFA), Body Investment Scale's (BIS), and Difficulties in Emotion Regulation Scale's (DERS) scores between GD adolescents (n = 30) and cisgenders (n = 30), (2) finding correlations between body investment and emotion regulation in the GD sample, (3) evaluating the link between these dimensions and internalizing symptomatology of GD adolescents. In addition to the significant impairment in emotion regulation and a negative body investment in the GD sample, Spearman's correlation analyses showed a relationship between worse body protection and impaired emotion regulation, and binary logistic regressions of these dimensions on each SAFA domain evidenced that they may have a role in the increased probability of pathological scores for depression. Our results focused on the role played by emotion regulation and emotional investment in the body in the exacerbating and maintenance of internalizing symptoms, in particular depression, and self-harming behaviors in GD adolescents.

Horizontal Gaze Palsy with Progressive Scoliosis with Overlapping Epilepsy and Learning Difficulties: A Case Report.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital disease characterized by the absence of horizontal gaze movements, progressive scoliosis, and typical brain, cerebellum, and medullary malformations. Here we describe a pediatric HGPPS case with overlapping epilepsy and learning difficulties. A 6-year-old girl was admitted to the University Hospital of Bari for the onset of a tonic-clonic seizure. Electroencephalogram showed slow and sharp waves on the right side with the tendency to diffuse. Brain magnetic resonance imaging demonstrated malformations compatible with HGPPS. Ophthalmological and orthopedic evaluations confirmed conjugate horizontal gaze palsy and mild thoracolumbar scoliosis. Neuropsychological assessment attested normal intelligence but serious difficulties in reading and writing. In spite of neuroradiological malformations, visual difficulties, and spinal deformities, literature data are limited about any coexisting neurocognitive HGPPS symptoms. Literature data regarding such topics are very limited. If, on the one hand, the coexistence of such symptoms can be interpreted as occasional, it could support the idea that they could fall within a spectrum of HGPPS anomalies. In addition to the standard investigations, the activation of specific neuropsychological assessment programs could help interventions improve the specialist care and the quality of life of HGPPS patients.

Methylphenidate Use for Emotional Dysregulation in Children and Adolescents with ADHD and ADHD and ASD: A Naturalistic Study.

Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough evidence about its use in ASD with comorbid ADHD. This naturalistic study aims to investigate the effectiveness of immediate- and extended-release MPH in the treatment of ED in 70 children and adolescents (6-18 years), with a diagnosis of ADHD (n = 41) and of ASD with comorbid ADHD (n = 29), using the Child Behavior Checklist-Attention/Aggressive/Anxious (CBCL-AAA). Their parents completed the CBCL twice-first during the summer medication-free period, that is, at least one month after drug interruption; and again after three months of treatment restart. Results demonstrate that MPH is associated with a statistically significant reduction in ED in ADHD and ASD, without substantial adverse events, supporting the use of psychostimulants for the treatment of ED in these neurodevelopmental disorders.

Depressive risk among Italian socioeconomically disadvantaged children and adolescents during COVID-19 pandemic: a cross-sectional online survey.

BACKGROUND: Children and adolescents and low-income individuals are considered particularly vulnerable for mental health implications during the current COVID-19 pandemic. Depression is a frequent negative emotional response during an epidemic outbreak and is also prone importantly to environmental risk like stressors derived from income inequality. We aimed to assess depressive symptomatology in a sample of Italian low-income minors during the COVID-19 outbreak. We hypothesized that the stronger were the negative effects of the pandemic on socioeconomic conditions, the higher would have been the risk for showing depressive symptoms. METHODS: We performed a cross-sectional study during July 2020, at the end of the Italian first wave of COVID-19 pandemic. We recruited 109 Italian socioeconomically disadvantaged children and adolescents from 7 to 17 years. We used an online survey to collect socio-demographic and clinical data and information about pandemic-related stressors and to assess depressive symptoms with the Children's Depression Inventory 2 (CDI 2), Parent Version (Emotional Problems subscale) and Self-Report Short Form. We performed logistic regression analysis to assess the association between depressive symptoms and potential risk factors for mental health. RESULTS: 22% and 14% of participants showed depressive symptoms at the CDI 2 Parent Version and Self-Report, respectively. Participants coming from families experiencing a lack of basic supplies during the pandemic (34.9%) were more expected to show depressive symptoms at CDI 2 Parent Version. Participants with a pre-existing neuropsychiatric diagnosis (26.6%) were more likely to exhibit depressive symptoms measured by CDI 2 Parent Version. CONCLUSIONS: The results of our study showed that a group of Italian socioeconomically disadvantaged children and adolescents were more vulnerable to depressive symptoms if they suffered from a paucity of essential supplies during the pandemic or had pre-existing neurodevelopmental disorders. The promotion of educational and child-care programs and activities could be crucial in sustaining the prevention of mental distress in those frail subjects who particularly need support outside the family. Further studies are needed to detect effective preventive and therapeutic strategies to adopt promptly in the case of another pandemic wave.

Association between autism spectrum disorder and diabetes: systematic review and meta-analysis.

There is mixed evidence on the link between autism spectrum disorder (ASD) and diabetes. We conducted the first systematic review/meta-analysis on their association. Based on a pre-registered protocol (PROSPERO: CRD42021261114), we searched Pubmed, Ovid, and Web of Science databases up to 6 December 2021, with no language/type of document restrictions. We assessed study quality using the Newcastle-Ottawa Scale (NOS). We included 24 studies (total: 3427,773 individuals; 237,529 with ASD and 92,832 with diabetes) in the systematic review and 20 in the meta-analysis (mean stars number on the NOS: 5.89/10). There was a significant association, albeit characterized by significant heterogeneity, when pooling unadjusted OR (1.535, 95% CI = 1.109-2.126), which remained significant when restricting the analysis to children and type 2 diabetes, but became non-significant when considering adjusted ORs (OR: 1.528, 95% CI = 0.954-2.448). No significant prospective association was found (n = 2) on diabetes predicting ASD (HR: 1.232, 0.826-11.837). Therefore, the association between ASD and diabetes is likely confounded by demographic and clinical factors that should be systematically investigated in future studies.

Assessing Clinical Features of Adolescents Suffering from Depression Who Engage in Non-Suicidal Self-Injury.

Depressive disorders (DDs) and non-suicidal self-injury (NSSI) are important juvenile mental health issues, showing alarming increasing rates. They frequently co-occur, mainly among adolescents, increasing the suicide risk. We aimed to compare the clinical features of two groups of adolescents with DDs, differed by their engagement or not in NSSI ("DD + NSSI" and "DD"). We hypothesized that NSSI would characterize particularly severe forms of DDs suitable for becoming specific phenotypes of adolescent depression. We enrolled 56 adolescents (11-17 years) diagnosed with a DD according to the DSM-5 criteria. They were assessed for NSSI endorsement (Ottawa Self-Injury Inventory), depressive symptoms (Children's Depression Inventory 2), emotional dysregulation (Difficulties in Emotional Regulation Scale), and anxiety symptoms (Screen for Child Anxiety-Related Emotional Disorders). The two groups accounted for 31 ("DD + NSSI") and 25 ("DD") individuals. The "DD + NSSI" group had significantly higher suicidal ideation (p 0.0039), emotional dysregulation (p 0.0092), depressive symptoms (p 0.0138), and anxiety symptoms (p 0.0153) than the "DD" group. NSSI seemed to characterize more severe phenotypes of adolescent depression, applying for a potential role as a "specifier" of DDs, describing relevant information for their management. Further studies are needed to support this hypothesis and its potential opportunities for prevention and treatment.

Clinical characterization of a novel RAB39B nonstop mutation in a family with ASD and severe ID causing RAB39B downregulation and study of a Rab39b knock down mouse model.

Autism spectrum disorder (ASD) and intellectual disability (ID) often exist together in patients. The RAB39B gene has been reported to be mutated in ID patients with additional clinical features ranging from ASD, macrocephaly, seizures and/or early-onset parkinsonism. Here, we describe a novel RAB39B nonstop mutation [Xq28; c.640 T > C; p.(*214Glnext*21)] in a family with ASD, severe ID and poor motor coordination, and we assessed the pathogenicity of the mutation. A heterologous cell system and a Rab39b knockdown (KD) murine model, which mimic the nonstop mutation, were used to validate the deleterious effect of the RAB39B mutation. The mutation led to RAB39B protein instability, resulting in its increased degradation and consequent downregulation. Using a Rab39b KD mouse model, we demonstrated that the downregulation of RAB39B led to increased GluA2 lacking Ca2+-permeable AMPAR composition at the hippocampal neuronal surface and increased dendritic spine density that remained in an immature filopodia-like state. These phenotypes affected behavioural performance in a disease-specific manner. Rab39b KD mice revealed impaired social behaviour but intact social recognition. They also showed normal anxiety-like, exploratory and motivational behaviours but impaired working and associative memories. In conclusion, we found a novel RAB39B nonstop variant that segregated in a family with a clinical phenotype including ID, ASD and poor motor coordination. The pathogenicity of mutations causing the downregulation of RAB39B proteins, impacting AMPAR trafficking and dendritic spine morphogenesis, reinforced the idea that AMPAR modulation and dendritic spine assets could be considered hallmarks of neurodevelopmental disorders.

Glucose and Lipid Profiles Predict Anthropometric Changes in Drug-Naïve Adolescents Starting Treatment with Risperidone or Sertraline: A Pilot Study.

Psychiatric disorders are associated with cardiometabolic diseases, partly due to adverse drug effects with individual risk variabilities. Risperidone and sertraline are widely used for youths. Although they may be exposed to anthropometric changes, few data about this population exist. We evaluated the correlation between several blood parameters and body changes in a very small group of drug-naïve adolescents who had started risperidone or sertraline. We examined weight, waist circumference (WC), WC/height ratio and body mass index (BMI) at baseline (T0) and after at least three months of therapy (T1), and blood glucose and lipid profiles at T0. Here, we show significant increases in several anthropometric parameters in both groups, a negative correlation between HDL and ΔWC in the risperidone group and positive correlations between insulin and ΔBMI and between HOMA-IR and ΔBMI in the sertraline group. Despite the sample size, these results are important because it is difficult to study adolescents who are long-term-compliant with psychotropic drugs. This pilot study supports the importance of future large-scale investigations to understand the metabolic risk profiles of psychotropic drugs, their individual vulnerabilities and their underlying mechanisms. Simultaneous guideline-based psychiatric and metabolic interventions should be part of daily practice.

Serum Neurofilament Light Chain Levels and Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Acquired Demyelinating Syndromes.

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS). Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab- and in two subgroups MOG-Ab+ with/without encephalopathy. Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17-17.5 vs. 14.7/9-17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab-. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab- (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8-1,129) and MOG-Ab- (median/range = 11.6/4.3-788) compared to age-matched controls (median/range = 2.98/1-4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17-11.17 vs. 14.16/9.8-17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1-1,129 vs. 10.22/6.83-50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04-0.69 vs. 0.05/0.04-0.28; p = 0.1) in comparison to those without encephalopathy. Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.