Search Results (69)

Epilepsy affects over 12 million children worldwide, with approximately 30% classified as having drug-resistant epilepsy (DRE), often accompanied by neuropsychiatric comorbidities that severely impact quality of life. The endocannabinoid system (ECS) functions as a multifaceted neuromodulatory network regulating neuronal excitability, synaptic plasticity, and immune homeostasis from early life through adolescence and into aging. In pediatric epilepsies, alterations in ECS components, particularly CB1 receptor expression and endocannabinoid levels, reveal disorder-specific vulnerabilities and therapeutic opportunities. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown strong preclinical and clinical efficacy in treating DRE and is approved for Dravet syndrome, Lennox–Gastaut syndrome, and Tuberous Sclerosis Complex. Other ECS-based strategies, such as the use of CB1 receptor-positive allosteric modulators, can selectively enhance endogenous cannabinoid signaling where and when it is active, potentially reducing seizures in conditions like Dravet and absence epilepsy. Similarly, FAAH and MAGL inhibitors may help restore ECS tone without directly activating CB1 receptors. Precision targeting of ECS components based on regional expression and syndrome-specific pathophysiology may optimize seizure control and associated comorbidities. Nonetheless, long-term pediatric use must be approached with caution, given the critical role of the ECS in brain development. Full article

The Default Mode Network has been extensively studied in recent decades due to its central role in higher cognitive processes and its relevance for understanding mental disorders. This neural network, characterized by synchronized and coherent activity at rest, is intrinsically linked to self-reflection, mental exploration, social interaction, and emotional processing. Our understanding of the DMN extends beyond humans to non-human animals, where it has been observed in various species, highlighting its evolutionary basis and adaptive significance throughout phylogenetic history. Additionally, the DMN plays a crucial role in brain development during childhood and adolescence, influencing fundamental cognitive and emotional processes. This literature review aims to provide a comprehensive overview of the DMN, addressing its structural, functional, and evolutionary aspects, as well as its impact from infancy to adulthood. By gaining a deeper understanding of the organization and function of the DMN, we can advance our knowledge of the neural mechanisms that underlie cognition, behavior, and mental health. This, in turn, can lead to more effective therapeutic strategies for a range of neuropsychiatric conditions. Full article

Background: The primary goal of our study is to assess the national US prevalence of autism spectrum disorder (ASD), along with its socio-demographic characteristics, severity, and co-occurring medical and psychiatric disorders, using data from the 2020–2021 National Survey of Children’s Health (NSCH). Methods: We analyzed 2020–2021 NSCH data to estimate the prevalence of ever-diagnosed and current ASD among 79,182 children and adolescents (3–17 years). Univariate and multivariate regression models were used to examine associations between medical and psychiatric co-morbidities, socio-demographic factors, and ASD severity. Results: Adolescents (11–17 years) and males were more likely to have ASD, with males comprising 78.7% of the ASD group. The mean age of the sample was 10.1 ± 4.6 years, and 3.2% had an ASD diagnosis. Children from lower-income households and those with caregivers who completed only a high school education were more likely to have ASD. Nearly 96.4% of children with ASD had at least one co-morbid condition. The most common neuropsychiatric co-morbidities were developmental delay (64%), behavioral and conduct problems (57.8%), and anxiety disorder (45.7%), while the most common medical conditions were allergies (32.4%), genetic disorders (26.2%), and asthma (12.6%). Gender disparities in ASD presentation were evident that females with ASD were more likely to experience vision problems, cerebral palsy, epilepsy, depression, and intellectual disability but had lower odds of ADHD and anxiety problems. Greater ASD severity was linked to higher odds of intellectual disability (OR: 5.8, p < 0.001), developmental delay (OR: 5.0, p < 0.001), epilepsy, Down syndrome (OR: 3.4, p < 0.001), vision problems (OR: 2.5, p < 0.001), and genetic disorders (OR: 2.3, p < 0.001). Conclusions: This study provides updated prevalence estimates of ASD and highlights the high burden of co-morbidities, emphasizing the need for comprehensive, multidisciplinary approaches in ASD management. Additionally, our findings emphasize gender differences in ASD presentation, which should be considered in future research and clinical practice to ensure more tailored diagnostic and intervention strategies. Full article

Background: Anorexia Nervosa (AN) is a severe Feeding and Eating Disorder (FED) that is more prevalent in females, often manifesting during adolescence. Recent research highlights an elevated presence of comorbid Autism Spectrum Disorder (ASD) traits among individuals with AN, with specific expressions in females accounting for sensorial and interoceptive experiences. This study retrospectively explores the association between ASD traits, eating symptomatology, and interoceptive deficits in Italian female adolescents with AN. Methods: A retrospective evaluation of female AN/Atypical AN patients (n = 52) aged 13–17 years was conducted at two university pediatric hospitals in Italy. The participants underwent neuropsychiatric assessments, including the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), and measurement of ASD traits with the Autism-spectrum quotient (AQ), camouflaging ASD traits Questionnaire (CAT-Q), Toronto Alexithymia Scale (TAS-20), and FED-symptomatology-related measures. Results: Overall, 9.6% of the participants exhibited an ADOS-2 clinical impression consistent with ASD. Higher scores in AQ and CAT-Q revealed ASD traits and camouflaging strategies. The interoceptive deficits positively correlated with the ASD traits, alexithymia, and camouflage, and TAS—Difficulty Identifying Feelings emerged as the sole predictor for interoceptive deficits. Discussion: This Italian study preliminarily underscores the importance of recognizing ASD traits in the AN population, emphasizing early intervention strategies. The intersection of alexithymia and interoceptive deficits emerges as a crucial nexus between ASD and AN, with potential therapeutic implications. Full article

Magnetic resonance imaging (MRI) is essential for studying brain development and psychiatric disorders in adolescents. However, the imaging consistency remains challenging, highlighting the need for advanced methodologies to improve the diagnostic and research reliability in this unique developmental period. Adolescence is marked by significant neuroanatomical changes, distinguishing adolescent brains from those of adults and making age-specific imaging research crucial for understanding the neuropsychiatric conditions in youth. This study examines the test–retest reliability of anatomical brain MRI scans in adolescents diagnosed with depressive disorders, emphasizing a developmental perspective on neuropsychiatric disorders. Using a sample of 42 adolescents, we assessed the consistency of structural imaging metrics across 95 brain regions with deep learning-based neuroimaging analysis pipelines. The results demonstrated moderate to excellent reliability, with the intraclass correlation coefficients (ICC) ranging from 0.57 to 0.99 across regions. Notably, regions such as the pallidum, amygdala, entorhinal cortex, and white matter hypointensities showed moderate reliability, likely reflecting the challenges in the segmentation or inherent anatomical variability unique to this age group. This study highlights the necessity of integrating advanced imaging technologies to enhance the accuracy and reliability of the neuroimaging data specific to adolescents. Addressing the regional variability and strengthening the methodological rigor are essential for advancing the understanding of brain development and psychiatric disorders in this distinct developmental stage. Future research should focus on larger, more diverse samples, multi-site studies, and emerging imaging techniques to further validate the neuroimaging biomarkers. Such advancements could improve the clinical outcomes and deepen our understanding of the neuropsychiatric conditions unique to adolescence. Full article

Background: Tobacco smoke exposure (TSE) is a major public health concern, impacting not only smokers but also those around them, particularly children and adolescents. TSE is linked to various neuropsychiatric conditions and significantly impacts quality of life. This study examines the prevalence, socio-demographic factors, and the impact of TSE on the severity of neurological and psychiatric co-morbidities. Methods: Data from the National Survey of Children’s Health (NSCH) in the US from 2020 to 2021 were used in this study. We included 91,404 children and adolescents aged between 0 to 17 years for the TSE prevalence and socio-demographic analysis, and 79,182 children and adolescents aged between 3 and 17 years for the neuropsychiatric co-morbidities analysis. The mean age of these individuals was 8.7 (standard deviation: 5.3), and 11,751 (12.9%) had confirmed TSE. Results: Our analysis showed that TSE is more common in males (53%) than females (47%). Additionally, the odds of TSE were higher in families with a lower income level and with American Indian/Native Alaska racial descent. We found that 36.4% of youths with TSE developed at least one co-morbid condition. The most common neuropsychiatric co-morbidities were anxiety problems (15.7%), Attention-Deficit Hyperactivity Disorder (ADHD) (15.5%), behavioral and conduct problems (13.7%), and learning disability (12%). Females had lower odds of co-morbid anxiety (OR: 0.3, p = 0.02) and Autism Spectrum Disorder (ASD) (OR: 0.9, p = 0.04) than males. Asians showed lower odds of co-morbid ADHD (OR: 0.3, p-value: 0.001), anxiety problems (OR: 0.4, p-value: 0.003), speech/other language disorder (OR: 0.4, p-value: 0.001), developmental delay (OR: 0.4, p-value: 0.001), behavioral and conduct problems (OR: 0.4, p-value: 0.003), and learning disability (OR: 0.5, p-value: 0.004). Conversely, American Indian children and adolescents had higher odds of co-morbid headaches (OR: 3, p-value: 0.005). TSE co-occurring with Tourette’s Syndrome (TS) (OR: 4.4, p < 0.001), ADHD (OR: 1.3, p < 0.001), developmental delay (OR: 1.3, p < 0.001), behavioral problems (OR: 1.3, p < 0.001), headaches (OR: 1.3, p = 0.005), depression (OR: 1.2, p = 0.02), anxiety (OR: 1.2, p < 0.01), ASD (OR: 1.2, p < 0.001), and learning disability (OR: 1.2, p = 0.03) may contribute to a more severe manifestation. Conclusions: ADHD, behavioral/conduct problems, and learning disabilities were the most prevalent co-occurring conditions with TSE. Our findings show that 36.4% of youths with TSE had at least one neuropsychiatric comorbidity. Screening for these conditions in youths exposed to TSE is crucial for early detection and interventions to increase their mental health and well-being. Full article

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson’s and Alzheimer’s diseases. This study aimed to establish the association between Fok1/Apa1 polymorphic variants and anxious/depressive symptoms in nonclinical adolescents from central Italy, with the goal of identifying the risk of developing both symptoms. We found no significant difference in genotype distribution or dominant/recessive models of Fok1/Apa1 VDR polymorphic variants between subjects with anxious/depressive symptoms and controls. HN9.10e cell lines carrying the AA genotype for Fok1 and the CC genotype for Apa1 responded better to treatment with vitamin D3 than cell lines carrying the AG genotype for Fok1 and CA genotype for Apa1. Cell lines carrying the GG genotype for Fok1 and the AA genotype for Apa1 did not respond at all, suggesting avenues for future studies in both the general population and individuals with mental and/or neuropsychiatric disorders. These studies suggest that the level of response to vitamin D3 administered to prevent and/or treat mental or neurological disorders could depend on the polymorphic variants of the vitamin D receptor. Full article

During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis. Full article

Background: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. Case presentation: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. Conclusions: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out. Full article

The NR4A2 gene encodes an orphan transcription factor of the steroid–thyroid hormone–retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson’s or Alzheimer’s disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence–young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox–Gastaut syndrome. Accordingly, we propose that NR4A2 should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy. Full article

Klinefelter syndrome (KS), characterized by an additional X-chromosome in males, manifests in a wide range of neuroendocrine and psychiatric symptoms. Individuals with KS often face increased risks of hormonal dysfunction, leading to depression and anxiety, although extended research during pediatric and adolescent age is still limited. This critical phase, decisive for KS children, is influenced by a combination of genetic, environmental and familial factors, which impact brain plasticity. In this report, we reviewed, in a narrative form, the crucial KS psychopathological hallmarks in children. To better describe neuroendocrine and neuropsychiatric outcomes in children with KS, we presented the case of an 11-year-old prepubertal child with mosaic KS who was referred to our Center of Developmental Psychopathology due to a decline in his academic performance, excessive daytime fatigue and increased distractibility over the past few months. Family history revealed psychiatric conditions among first- and second-degree relatives, including recently divorced parents and a 15-year-old sister. Early-onset persistent depressive disorder and anxious traits were diagnosed. Timely identification of susceptible children, with thorough examination of familial psychiatric history, environmental influences and neurocognitive profile, alongside targeted interventions, could potentially mitigate lifelong psychopathology-related disabilities in pediatric and adolescent KS cases, including those with mosaic KS. Full article

Background: Sotos syndrome is a genetic disorder caused by NSD1 gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly, learning disabilities, and co-occurring neuropsychiatric symptoms. Methods: Literature sources published in 2002–2023 were selected and analyzed from PubMed and Google Scholar databases. Results: Neuropsychiatric symptoms are observed among children and adolescents with Sotos syndrome. The majority have intellectual disabilities or borderline intellect. Verbal IQ is higher than performance IQ. Individuals display difficulties in expressing language. Aggression is reported by parents. Children express autistic behavior, ADHD, anxiety based on phobias, and early bedtime-wake times. Conclusions: Sotos syndrome is associated with neuropsychiatric disorders in children. Slow intellectual and language development, aggressive outbursts, anxiety, autism spectrum disorder, and hyperactivity are present in the newest studies. Comprehensive assistance is needed for Sotos syndrome patients in responding to areas of difficulty. There is still a lack of research on the developmental characteristics of these children and the possibilities of improving psychosocial adaptation by providing multidisciplinary long-term medical, educational, and social care. Full article

Mental disorders account for one of the most prevalent categories of the burden of disease worldwide, with depression expected to be the largest contributor by 2030, closely followed by anxiety. The COVID-19 pandemic possibly exacerbated these challenges, especially amongst adolescents, who experienced isolation, disrupted routines, and limited healthcare access. Notably, the pandemic has been associated with long-term neurological effects known as “long-COVID”, characterized by both cognitive and psychopathological symptoms. In general, psychiatric disorders, including those related to long-COVID, are supposed to be due to widespread inflammation leading to neuroinflammation. Recently, the endocannabinoid system (ECS) emerged as a potential target for addressing depression and anxiety pathophysiology. Specifically, natural or synthetic cannabinoids, able to selectively interact with cannabinoid type-2 receptor (CB2R), recently revealed new therapeutic potential in neuropsychiatric disorders with limited or absent psychotropic activity. Among the most promising natural CB2R ligands, the bicyclic sesquiterpene β-caryophyllene (BCP) has emerged as an excellent anti-inflammatory and antioxidant therapeutic agent. This review underscores BCP’s immunomodulatory and anti-inflammatory properties, highlighting its therapeutic potential for the management of depression and anxiety. Full article

Non-Suicidal Self-Injury (NSSI) involves deliberately causing harm to one’s body without the intention of suicide. As the numbers of adolescents presenting NSSI have been steadily increasing during the last years, we intended to investigate adolescent patients exhibiting NSSI, admitted to our clinic—a Romanian child psychiatry inpatient clinic, over the course of five years. A total of 100 adolescents (80 females, 20 males, mean age: 14.9 years) hospitalized for various neuropsychiatric disorders and engaging in self-harm were studied. The self-harm methods most frequently used in our sample were, for the female group: cutting (all), skin tearing (76%), scratching/pinching (72%), and for males: cutting (all), wound-healing hindrance (85%), striking objects (80%). The initial motivations for NSSI were represented by distress (females 89%, males 90%) and seeking pleasure (females 84%). In terms of the roles of NSSI, it was primarily used for emotional regulation (females 89%) and anger management (males 90%). This study highlights the prevalence of self-harm in hospitalized adolescents, differences in methods and motivations between genders, and the need for more targeted therapy interventions. By documenting trends, investigating underlying motivations and functions, and proposing hypotheses for further research, our findings offer valuable insights on adolescent NSSI and have the potential to increase awareness among various clinicians and specialists who interact with adolescents, thus addressing the escalating prevalence of self-harm behaviours among teenagers. Full article

The UNC-5 family of netrin receptor genes, predominantly expressed in brain tissues, plays a pivotal role in various neuronal processes. Mutations in genes involved in axon development contribute to a wide spectrum of human diseases, including developmental, neuropsychiatric, and neurodegenerative disorders. The NTN1/DCC signaling pathway, interacting with UNC5C, plays a crucial role in central nervous system axon guidance and has been associated with psychiatric disorders during adolescence in humans. Whole-exome sequencing analysis unveiled two compound heterozygous causative mutations within the UNC5C gene in a patient diagnosed with psychiatric disorders. In silico analysis demonstrated that neither of the observed variants affected the allosteric linkage between UNC5C and NTN1. In fact, these mutations are located within crucial cytoplasmic domains, specifically ZU5 and the region required for the netrin-mediated axon repulsion of neuronal growth cones. These domains play a critical role in forming the supramodular protein structure and directly interact with microtubules, thereby ensuring the functionality of the axon repulsion process. We emphasize that these mutations disrupt the aforementioned processes, thereby associating the UNC5C gene with psychiatric disorders for the first time and expanding the number of genes related to psychiatric disorders. Further research is required to validate the correlation of the UNC5C gene with psychiatric disorders, but we suggest including it in the genetic analysis of patients with psychiatric disorders. Full article