Autonomic and hedonic response to affective touch in autism spectrum disorder.

Interpersonal touch plays a crucial role in shaping relationships and encouraging social connections. Failure in processing tactile input or abnormal tactile sensitivity may hamper social behaviors and have severe consequences in individuals' relational lives. Autism Spectrum Disorder (ASD) is characterized by both sensory disruptions and social impairments, making affective touch an ideal meeting point for understanding these features in ASD individuals. By integrating behavioral and physiological measures, we investigated the effects of affective touch on adult individuals with ASD from both an implicit and explicit perspective. Specifically, at an implicit level, we investigated whether and how receiving an affective touch influenced participants' skin conductance tonic and phasic components. At the explicit level, we delved into the affective and unpleasant features of affective touch. Overall, we observed lower skin conductance level in ASD compared to TD subjects. Interestingly, the typically developing (TD) group showed an increased autonomic response for affective touch compared to a control touch, while ASD subjects' autonomic response did not differ between the two conditions. Furthermore, ASD participants provided higher ratings for both the affective and unpleasant components of the touch, compared to TD subjects. Our results reveal a noteworthy discrepancy in ASD population between the subjective experience, characterized by amplified hedonic but also unpleasant responses, and the physiological response, marked by a lack of autonomic activation related to affective touch. This insightful dissociation seems crucial for a deeper understanding of the distinctive challenges characterizing people with ASD and may have implications for diagnosis and therapeutic approaches.

Atypical local brain connectivity in pediatric autism spectrum disorder? A coordinate-based meta-analysis of regional homogeneity studies.

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age [Formula: see text] 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.

Diagnostic assessment, therapeutic care and education pathways in persons with autism spectrum disorder in transition from childhood to adulthood: the Italian National Ev.A Longitudinal Project.

INTRODUCTION: The transition from childhood to adulthood is one of the main critical points in the network of services for taking care of people with autism spectrum disorder (ASD). Within the framework of the national research programs on autism, an exploratory longitudinal multicentre study was conducted. This research program, called "Ev.A Project (Developmental and Adult Age)", was proposed by the Italian National Institute of Health (Istituto Superiore di Sanità, ISS) and the aim was the development and testing of a diagnostic, therapeutic, assistance and educational pathway (PDTAE) for autism. AIM: The present study aimed to evaluate two impact outcomes of the care protocol: the response obtained by the ASD person, and the perception of the change in the family context. METHODS: Participants underwent an initial clinical evaluation and then after one year. Over the course of the year, participants undertook a program of intervention. The measures of adaptive functioning, need for support, psychiatric symptomatology and family quality of life were used for the outcome assessment. Linear mixed models were constructed for each measure to estimate the explanatory/predictive behavior of the intensity of the interventions, adjusted for the participant's level of symptom severity. RESULTS: The results estimate a main effect of Intervention Group (b=-27.22, p<0.001) and severity level (b=-41.87, p<0.001) on the adaptive functioning of the ASD person, but no effect on performance on the dimension of Family Quality of Life (b=0.523, p=0.455). CONCLUSIONS: The most significant predictor of the impact on the ASD person is the activation of the service network, which must take into account the level of severity of the presented symptoms.

Pregnancy in autistic women and social medical considerations: scoping review and meta- synthesis.

Introduction: This article addresses a topic that has been largely overlooked by scientific literature, namely pregnancy in autistic women. Generally, the issue of sexuality in disability, particularly in disabled women, autistic or otherwise, has been underexplored. However, it is necessary to scientifically investigate this topic to propose adequate social and health policies. Therefore, we chose to conduct a scoping review to answer three main questions: "What does it mean for an autistic woman to be pregnant?"; "How do these two conditions coexist?"; "Are health services prepared to receive this population adequately or does autism become a stigma for pregnant women?" Methods: We conducted a systematic review and qualitative thematic synthesis following the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analyses on autistic women and pregnancy in the last 10 years. Results: The studies included in our review are 7, extremely diverse in terms of methodologies and sample sizes. Despite the heterogeneity of samples and methodologies, all research tends to highlight the following results. For autistic women during pregnancy, three areas seem to be the most difficult: sensory issues, mood disorders, and relationships with specialists. Discussion: Our study found that women with ASD face unique challenges during childbirth that differ from those of neurotypical women. Participants often felt belittled, ignored, and uninformed about the care they received, and being placed at the centre of attention was often seen as negative and hindering rather than positive. However, the research shows us how some "expected" results, such as difficulties in breastfeeding, have been disproven.

Investigating the impact of disposable surgical face-masks on face identity and emotion recognition in adults with autism spectrum disorder.

With the outburst of the COVID-19 pandemic, disposable surgical face-masks (DSFMs) have been widely adopted as a preventive measure. DSFMs hide the bottom half of the face, thus making identity and emotion recognition very challenging, both in typical and atypical populations. Individuals with autism spectrum disorder (ASD) are often characterized by face processing deficits; thus, DSFMs could pose even a greater challenge for this population compared to typically development (TD) individuals. In this study, 48 ASDs of level 1 and 110 TDs underwent two tasks: (i) the Old-new face memory task, which assesses whether DSFMs affect face learning and recognition, and (ii) the Facial affect task, which explores DSFMs' effect on emotion recognition. Results from the former show that, when faces were learned without DSFMs, identity recognition of masked faces decreased for both ASDs and TDs. In contrast, when faces were first learned with DSFMs, TDs but not ASDs benefited from a "context congruence" effect, that is, faces wearing DSFMs were better recognized if learned wearing DSFMs. In addition, results from the Facial affect task show that DSFMs negatively impacted specific emotion recognition in both TDs and ASDs, although differentially between the two groups. DSFMs negatively affected disgust, happiness and sadness recognition in TDs; in contrast, ASDs performance decreased for every emotion except anger. Overall, our study demonstrates a general, although different, disruptive effect on identity and emotion recognition both in ASD and TD population.

Revealing the Selectivity of Neuroanatomical Alteration in Autism Spectrum Disorder via Reverse Inference.

BACKGROUND: Although neuroimaging research has identified atypical neuroanatomical substrates in individuals with autism spectrum disorder (ASD), it is at present unclear whether and to what extent disorder-selective gray matter alterations occur in this spectrum of conditions. In fact, a growing body of evidence shows a substantial overlap between the pathomorphological changes across different brain diseases, which may complicate identification of reliable neural markers and differentiation of the anatomical substrates of distinct psychopathologies. METHODS: Using a novel data-driven and Bayesian methodology with published voxel-based morphometry data (849 peer-reviewed experiments and 22,304 clinical subjects), this study performs the first reverse inference investigation to explore the selective structural brain alteration profile of ASD. RESULTS: We found that specific brain areas exhibit a >90% probability of gray matter alteration selectivity for ASD: the bilateral precuneus (Brodmann area 7), right inferior occipital gyrus (Brodmann area 18), left cerebellar lobule IX and Crus II, right cerebellar lobule VIIIA, and right Crus I. Of note, many brain voxels that are selective for ASD include areas that are posterior components of the default mode network. CONCLUSIONS: The identification of these spatial gray matter alteration patterns offers new insights into understanding the complex neurobiological underpinnings of ASD and opens attractive prospects for future neuroimaging-based interventions.

Genetic variants in DDX53 contribute to Autism Spectrum Disorder associated with the Xp22.11 locus.

Autism Spectrum Disorder (ASD) exhibits an ~4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exon PTCHD1 gene, an adjacent multi-isoform long noncoding RNA (lncRNA) named PTCHD1-AS (spanning ~1Mb), and a poorly characterized single-exon RNA helicase named DDX53 that is intronic to PTCHD1-AS. While the relationship between PTCHD1/PTCHD1-AS and ASD is being studied, the role of DDX53 has not been examined, in part because there is no apparent functional murine orthologue. Through clinical testing, here, we identified 6 males and 1 female with ASD from 6 unrelated families carrying rare, predicted-damaging or loss-of-function variants in DDX53. Then, we examined databases, including the Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, as well as population controls. We identified 24 additional individuals with ASD harboring rare, damaging DDX53 variations, including the same variants detected in two families from the original clinical analysis. In this extended cohort of 31 participants with ASD (28 male, 3 female), we identified 25 mostly maternally-inherited variations in DDX53, including 18 missense changes, 2 truncating variants, 2 in-frame variants, 2 deletions in the 3' UTR and 1 copy number deletion. Our findings in humans support a direct link between DDX53 and ASD, which will be important in clinical genetic testing. These same autism-related findings, coupled with the observation that a functional orthologous gene is not found in mouse, may also influence the design and interpretation of murine-modelling of ASD.

A case report and literature review of cognitive malingering and psychopathology.

Malingering of cognitive difficulties constitutes a major issue in psychiatric forensic settings. Here, we present a selective literature review related to the topic of cognitive malingering, psychopathology and their possible connections. Furthermore, we report a single case study of a 60-year-old man with a long and ongoing judicial history who exhibits a suspicious multi-domain neurocognitive disorder with significant reduction of autonomy in daily living, alongside a longtime history of depressive symptoms. Building on this, we suggest the importance of evaluating malingering conditions through both psychiatric and neuropsychological assessment tools. More specifically, the use of Performance Validity Tests (PVTs)-commonly but not quite correctly considered as tests of "malingering"-alongside the collection of clinical history and the use of routine psychometric testing, seems to be crucial in order to detect discrepancies between self-reported patient's symptoms, embedded validity indicators and psychometric results.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Real-Life Social-Skills Training and Motor-Skills Training in Adults With Autism Spectrum Disorder: The Con-Tatto Project Walking Down the Francigena Route.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an early onset and a genetic and epigenetic component. ASD is characterized by deficits in socio-emotional reciprocity, impaired verbal and non-verbal communication skills, and specific difficulties in developing and maintaining adequate social relationships with peers. Indeed, restricted, repetitive patterns of behavior, interests, or activities are required by DSM-5 diagnostic criteria. Autistic people usually need an unchanging environment (or in any case predictable and stable) and may have hypo- or hyper-sensitivity to sensory inputs. The onset of clinical symptoms occurs during the early years of life. Social skills competence is a significant therapeutic aim to be pursued when addressing ASD core symptoms. Several considerable motor difficulties (87%) in people with autism spectrum disorder in adulthood have been found. The Con-tatto project developed a project addressing social, physical, and mental health difficulties in real-life walking down the Francigena route for 9 days with 12 autistic people, by (1) Implementing daily sessions of social skills training program whose abilities were addressed to be immediately generalized and used throughout the day. (2) Educational movement and walking activity programs were led by a fitness coach. (3) The creation of walking peers' social community with a strong and relevant impact on adults with ASD social life respecting every person's individuality. (4) Provision of social reinforcers to reduce the stigma of people with autism and the experienced perception of low self-esteem, especially when they are bullied.

The Effect of Sleep-Wake Routines on the Negative Emotional States and Aggressive Behaviors in Adults with Autism Spectrum Disorders (ASD) during the COVID-19 Outbreak.

Disruption in routine may be related to experiencing negative emotional states and to aggressive behaviors in individuals with Autism Spectrum Disorder (ASD). The lockdown because of COVID-19 contributed to the disruption of individuals' routines, including the sleep−wake cycle. The current study tested a relationship between the adherence to the sleep−wake routine and aggressive behaviors via the mediation role of negative emotional states (i.e., anxiety and anger). Forty-three parents of adults with ASD completed a web-based questionnaire about their life condition during the first lockdown (April−May 2020). Preliminary analyses showed a worsening in the adults' aggressive behaviors during the lockdown in comparison to before it (Z = −3.130; p = 0.002). In the mediation models, the relationship between the adherence to the sleep−wake routines and aggressive behaviors was significant. The models showed the hypothesized mediated relationships among the adherence to the sleep−wake routines, negative emotional states, and aggressive behaviors (Model 1: F (1, 41) = 10.478, p < 0.001; Model 2: F(1, 41) = 9.826, p = 0.003). The findings confirmed the potential protective role of the adherence to the sleep−wake routines for the emotional and behavioral adjustment of adults with autism. Theoretical and practical contributions of the study were discussed; indeed, our results may inform parent-coaching as well as intervention programs for individuals with ASD given that adequate sleep hygiene may contribute to improvements in internalizing/externalizing behaviors.

Efficacy and Safety of Q10 Ubiquinol With Vitamins B and E in Neurodevelopmental Disorders: A Retrospective Chart Review.

Increased oxidative stress and defective mitochondrial functioning are shared features among many brain disorders. The aim of this study was to verify retrospectively the clinical efficacy and safety of a metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins in various neurodevelopmental disorders. This retrospective chart review study included 59 patients (mean age 10.1 ± 1.2 y.o., range 2.5-39 years; M:F = 2.47:1), diagnosed with Autism Spectrum Disorder (n = 17), Autism Spectrum Disorder with co-morbid Intellectual Disability (n = 19), Intellectual Disability or Global Developmental Delay (n = 15), Attention-Deficit/Hyperactivity Disorder (n = 3) and Intellectual Disability in Phelan-McDermid syndrome due to chr. 22q13.33 deletion (n = 5). After a minimum of 3 months of therapy, a positive outcome was recorded in 45/59 (76.27%) patients, with Clinical Global Impression-Improvement scores ranging between 1 ("very much improved") and 3 ("minimally improved"). The most widespread improvements were recorded in cognition (n = 26, 44.1%), adaptative functioning (n = 26, 44.1%) and social motivation (n = 19, 32.2%). Improvement rates differed by diagnosis, being observed most consistently in Phelan-McDermid Syndrome (5/5, 100%), followed by Intellectual Disability/Global Developmental Delay (13/15, 86.7%), Autism Spectrum Disorder with co-morbid Intellectual Disability (15/19, 78.9%), Autism Spectrum Disorder (11/17, 64.7%) and ADHD (1/3, 33.3%). No significant adverse event or side effect leading to treatment discontinuation were recorded. Mild side effects were reported in 18 (30.5%) patients, with the most frequent being increased hyperactivity (9/59, 15.3%). This retrospective chart review suggests that metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins is well tolerated and produces some improvement in the majority of patients with neurodevelopmental disorders, especially in the presence of intellectual disability. Randomized controlled trials for each single neurodevelopmental disorder are now warranted to conclusively demonstrate the efficacy of these mitochondrial bioenergetic and antioxidant agents and to estimate their therapeutic effect size.

Qualitative Differences in Attribution of Mental States to Other People in Autism and Schizophrenia: What are the Tools for Differential Diagnosis?

The differential diagnosis between schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD) remains an important clinical question, because they have overlap in clinical diagnosis. This study explored the differences between ASD (n = 44) and SSD patients (n = 59), compared to typically developing peers (n = 63), in completing an advanced Theory of Mind (ToM) task. The outcome found several differences between groups. The SSD patients showed greater difficulty in understanding social scenarios, while ASD individuals understood the stories, but did not correctly identify the protagonist's intention. The interesting aspect of the results is that some ToM stories are more informative about the mentalistic reasoning of the two clinical groups, namely, the stories that investigate pretend, persuasion, double bluff and ironic joke constructs.

Stereotypies in the Autism Spectrum Disorder: Can We Rely on an Ethological Model?

BACKGROUND: Stereotypic behaviour can be defined as a clear behavioural pattern where a specific function or target cannot be identified, although it delays on time. Nonetheless, repetitive and stereotypical behaviours play a key role in both animal and human behaviour. Similar behaviours are observed across species, in typical human developmental phases, and in some neuropsychiatric conditions, such as Autism Spectrum Disorder (ASD) and Intellectual Disability. This evidence led to the spread of animal models of repetitive behaviours to better understand the neurobiological mechanisms underlying these dysfunctional behaviours and to gain better insight into their role and origin within ASD and other disorders. This, in turn, could lead to new treatments of those disorders in humans. METHOD: This paper maps the literature on repetitive behaviours in animal models of ASD, in order to improve understanding of stereotypies in persons with ASD in terms of characterization, pathophysiology, genomic and anatomical factors. RESULTS: Literature mapping confirmed that phylogenic approach and animal models may help to improve understanding and differentiation of stereotypies in ASD. Some repetitive behaviours appear to be interconnected and mediated by common genomic and anatomical factors across species, mainly by alterations of basal ganglia circuitry. A new distinction between stereotypies and autotypies should be considered. CONCLUSIONS: Phylogenic approach and studies on animal models may support clinical issues related to stereotypies in persons with ASD and provide new insights in classification, pathogenesis, and management.

Psychological Impact of COVID-19 Outbreak on Families of Children with Autism Spectrum Disorder and Typically Developing Peers: An Online Survey.

BACKGROUND: When COVID-19 was declared as a pandemic, many countries imposed severe lockdowns that changed families' routines and negatively impacted on parents' and children's mental health. Several studies on families with children with autism spectrum disorder (ASD) revealed that lockdown increased the difficulties faced by individuals with ASD, as well as parental distress. No studies have analyzed the interplay between parental distress, children's emotional responses, and adaptive behaviors in children with ASD considering the period of the mandatory lockdown. Furthermore, we compared families with children on the spectrum and families with typically developing (TD) children in terms of their distress, children's emotional responses, and behavioral adaptation. METHODS: In this study, 120 parents of children aged 5-10 years (53 with ASD) participated. RESULTS: In the four tested models, children's positive and negative emotional responses mediated the impact of parental distress on children's playing activities. In the ASD group, parents reported that their children expressed more positive emotions, but fewer playing activities, than TD children. Families with children on the spectrum reported greater behavioral problems during the lockdown and more parental distress. CONCLUSIONS: Our findings inform the interventions designed for parents to reduce distress and to develop coping strategies to better manage the caregiver-child relationship.

Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review.

De novo variants in the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. This condition is an ultra-rare autosomal dominant neurodevelopmental disorder characterized by a broad range of clinical signs, including intellectual disability (ID), developmental delay (DD), seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies. Currently, 18 cases have been reported in the literature and for only 15 of them a clinical description is available. Here, we describe a child with Skraban-Deardorff syndrome associated with the WDR26 pathogenic de novo variant NM_025160.6:c.69dupC, p.(Gly24ArgfsTer48), and an adult associated with the pathogenic de novo variant c.1076G > A, p.(Trp359Ter). The adult patient was a 29-year-old female with detailed information on clinical history and pharmacological treatments since birth, providing an opportunity to map disease progression and patient management. By comparing our cases with published reports of Skraban-Deardorff syndrome, we provide a genetic and clinical summary of this ultrarare condition, describe the clinical management from childhood to adult age, and further expand on the clinical phenotype.

Gray matter abnormalities follow non-random patterns of co-alteration in autism: Meta-connectomic evidence.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by atypical brain anatomy and connectivity. Graph-theoretical methods have mainly been applied to detect altered patterns of white matter tracts and functional brain activation in individuals with ASD. The network topology of gray matter (GM) abnormalities in ASD remains relatively unexplored. METHODS: An innovative meta-connectomic analysis on voxel-based morphometry data (45 experiments, 1,786 subjects with ASD) was performed in order to investigate whether GM variations can develop in a distinct pattern of co-alteration across the brain. This pattern was then compared with normative profiles of structural and genetic co-expression maps. Graph measures of centrality and clustering were also applied to identify brain areas with the highest topological hierarchy and core sub-graph components within the co-alteration network observed in ASD. RESULTS: Individuals with ASD exhibit a distinctive and topologically defined pattern of GM co-alteration that moderately follows the structural connectivity constraints. This was not observed with respect to the pattern of genetic co-expression. Hub regions of the co-alteration network were mainly left-lateralized, encompassing the precuneus, ventral anterior cingulate, and middle occipital gyrus. Regions of the default mode network appear to be central in the topology of co-alterations. CONCLUSION: These findings shed new light on the pathobiology of ASD, suggesting a network-level dysfunction among spatially distributed GM regions. At the same time, this study supports pathoconnectomics as an insightful approach to better understand neuropsychiatric disorders.

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift.

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called 'First 1000 Days') are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

The Gut-Brain-Immune Axis in Autism Spectrum Disorders: A State-of-Art Report.

The interest elicited by the large microbial population colonizing the human gut has ancient origins and has gone through a long evolution during history. However, it is only in the last decades that the introduction of high-throughput technologies has allowed to broaden this research field and to disentangle the numerous implications that gut microbiota has in health and disease. This comprehensive ecosystem, constituted mainly by bacteria but also by fungi, parasites, and viruses, is proven to be involved in several physiological and pathological processes that transcend the intestinal homeostasis and are deeply intertwined with apparently unrelated body systems, such as the immune and the nervous ones. In this regard, a novel speculation is the relationship between the intestinal microbial flora and the pathogenesis of some neurological and neurodevelopmental disorders, including the clinical entities defined under the umbrella term of autism spectrum disorders. The bidirectional interplay has led researchers to coin the term gut-brain-immune system axis, subverting the theory of the brain as an immune-privileged site and underscoring the importance of this reciprocal influence already from fetal life and especially during the pre- and post-natal neurodevelopmental process. This revolutionary theory has also unveiled the possibility to modify the gut microbiota as a way to treat and even to prevent different kinds of pathologies. In this sense, some attempts have been made, ranging from probiotic administration to fecal microbiota transplantation, with promising results that need further elaboration. This state-of-art report will describe the main aspects regarding the human gut microbiome and its specific role in the pathogenesis of autism and its related disorders, with a final discussion on the therapeutic and preventive strategies aiming at creating a healthy intestinal microbial environment, as well as their safety and ethical implications.

Autism spectrum disorder and personality disorders: Comorbidity and differential diagnosis.

BACKGROUND: Differential diagnosis, comorbidities and overlaps with other psychiatric disorders are common among adults with autism spectrum disorder (ASD), but clinical assessments often omit screening for personality disorders (PD), which are especially common in individuals with high-functioning ASD where there is less need for support. AIM: To summarize the research findings on PD in adults with ASD and without intellectual disability, focusing on comorbidity and differential diagnosis. METHODS: PubMed searches were performed using the key words "Asperger's Syndrome", "Autism", "Personality", "Personality disorder" and "comorbidity" in order to identify relevant articles published in English. Grey literature was identified through searching Google Scholar. The literature reviews and reference sections of selected papers were also examined for additional potential studies. The search was restricted to studies published up to April 2020. This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. RESULTS: The search found 22 studies carried out on ASD adults without intellectual disability that met the inclusion criteria: 16 evaluated personality profiles or PD in ASD (comorbidity), five compared ASD and PD (differential diagnosis) and one performed both tasks. There were significant differences in the methodological approaches, including the ASD diagnostic instruments and personality measures. Cluster A and cluster C PD are the most frequent co-occurring PD, but overlapping features should be considered. Data on differential diagnosis were only found with cluster A and cluster B PD. CONCLUSION: ASD in high-functioning adults is associated with a distinct personality profile even if variability exists. Further studies are needed to explore the complex relationship between ASD and PD.