Increasing evidence indicates that human endogenous retroviruses (HERVs) are important to human health and are an underexplored component of many diseases. Certain HERV families show unique expression patterns and immune responses in autism spectrum disorder (ASD) patients compared to healthy controls, suggesting their potential as biomarkers. Despite these interesting findings, the role of HERVs in ASD needs to be further investigated. In this review, we discuss recent advances in genetic research on ASD, with a particular emphasis on the implications of HERVs on neurodevelopment and future genomic initiatives aimed at discovering ASD-related genes through Artificial Intelligence. Given their pro-inflammatory and autoimmune characteristics, the existing literature suggests that HERVs may contribute to the onset or worsening of ASD in individuals with a genetic predisposition. Therefore, we propose that investigating their fundamental properties could not only improve existing therapies but also pave the way for new therapeutic strategies.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent social communication difficulties, restricted interests, repetitive behaviors, and frequent medical comorbidities. Although early brain development in ASD has been extensively investigated, its biological progression across adulthood and aging remains largely unexplored. Growing evidence suggests that perivascular space (PVS) abnormalities may indicate impaired neurovascular integrity and reduced glymphatic clearance in ASD. Enlarged perivascular spaces (ePVS) in children commonly present alongside increased extra-axial CSF accumulation and more severe clinical manifestations, consistent with early alterations in CSF homeostasis and neuroimmune signaling. However, whether these abnormalities persist or evolve with aging remains unknown. Given that glymphatic and vascular integrity decline with age, and adults with ASD show elevated rates of sleep, metabolic, and cardiovascular disorders, PVS alterations may represent a unifying mechanism linking early neurodevelopmental divergence with later neurovascular vulnerability and cognitive aging. Advances in ultra-high-field MRI and automated segmentation now enable precise in vivo quantification of PVS burden, offering new opportunities for lifespan studies. By combining structural and functional methodologies, researchers may determine whether PVS constitute enduring traits, dynamic indicators of disease, or actionable therapeutic targets. Understanding their trajectories could provide critical insights into the continuum between neurodevelopmental and neurodegenerative phenomena in autism.

Background/Objectives: The severity of autism spectrum disorder (ASD) is clinically assessed through a comprehensive evaluation of social communication deficits, restricted interests, repetitive behaviors, and the level of support required (ranging from level 1 to level 3) according to DSM-5 criteria. Along with its varied clinical manifestations, the neuroanatomy of ASD is characterized by heterogeneous abnormalities. Notably, brain MRI of children with ASD often reveals an increased number of perivascular spaces (PVSs) compared to typically developing children. Our recent findings indicate that enlarged PVSs (ePVSs) are more common in younger male patients with severe ASD and that specific ePVS locations are significantly associated with ASD symptoms. Methods: In this study, we mapped ePVSs across key regions of three major cognitive networks—the Default Mode Network (DMN), the combined Central Executive/Frontoparietal Network (CEN/FPN), and the Salience Network (SN)—in 36 individuals with different symptom severities and rehabilitation needs due to ASD. We explored how the number, size, and location of PVSs in these networks are related to specific ASD symptoms and the overall need for rehabilitation and support. Results: Our results suggest that ePVSs in the DMN, CEN/FPN, and SN are strongly correlated with the severity of certain ASD symptoms, including verbal deficits, stereotypies, and sensory disturbances. We found a mild association between ePVSs and the level of support needed for daily living and quality of life. Conclusions: Dysfunction in cognitive networks associated with the presence of ePVSs has a significant impact on the severity of ASD symptoms. However, the need for assistance may also be influenced by other comorbid conditions and dysfunctions in smaller, overlapping brain networks.

Background The severity of autism spectrum disorder (ASD) is clinically assessed through a comprehensive evaluation of social communication deficits, restricted interests, repetitive behaviors, and the level of support required (ranging from level 1 to level 3), according to DSM-5 criteria. Along with its varied clinical manifestations, the neuroanatomy of ASD is characterized by heterogeneous abnormalities. Notably, brain MRI of children with ASD often reveal an increased number of perivascular spaces (PVS) compared to typically developing children. Our recent findings indicate that enlarged PVS (ePVS) are more common in younger male patients with severe ASD, and that specific ePVS locations are significantly associated with ASD symptoms. Objectives In this study, we mapped ePVS across key regions of three major cognitive networks: the default mode network (DMN), the combined central executive/frontoparietal network (CEN/FPN), and the salience network (SN) in 36 individuals with different symptoms severity and rehabilitation needs due to ASD. We explored how the number, size, and location of PVS in these networks are related to specific ASD symptoms and the overall need for rehabilitation and support. Results Our results suggest that ePVS in the DMN, CEN/FPN, and SN are strongly correlated with the severity of certain ASD symptoms, including verbal deficits, stereotypies, and sensory disturbances. We found a mild association between ePVS and the level of support needed for daily living and quality of life. Conclusion Dysfunction in cognitive networks associated with the presence of ePVS has a significant impact on the severity of ASD symptoms. However, the need for assistance may also be influenced by other comorbid conditions and dysfunctions in smaller, overlapping brain networks.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.