Gut to brain interaction in Autism Spectrum Disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters

Background: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. Methods: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. Discussion: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. Trial registration: ClinicalTrials.gov Identifier: NCT02708901. Retrospectively registered: March 4, 2016

Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder

Background: Recent investigations suggest a possible common genetic background between Autism Spectrum Disorders (ASD) and Celiac Disease (CD). However, studies regarding this association are scarce and often limited by the small sample sizes and/or large heterogeneity among ASD groups in terms of demographic and clinical features. The present study aims to investigate the overall CD prevalence (biopsy proven-CD patients plus screening detected tTG and EMA positive cases) in a large population of pre-schoolers with ASD referred to a tertiary care University Hospital. Methods: We retrospectively collected data about 382 children (mean age: 46.97 ± 13.55 months; age-range: 18-72 months) consecutively diagnosed as ASD (according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) over the period 2010-2013, and who performed a serological CD screening. Results: The overall CD prevalence was 2.62%, which is statistically significant higher to that reported in the Italian paediatric population (p = 0.0246). Half of these children had no symptoms or risk factors related to CD when they performed the serological screening. Conclusions: If replicated, these data suggest the importance of regular screening for CD in young patients with ASD, and are of relevance for clinical and public health

Conventional echo color Doppler versus ULA-OP in the assessment of venous flow model

The quantification of venous flows can be obtained by multiplying cross sectional area, measured on a B-mode video-clip, by velocity values, obtained with Doppler measurements. The Doppler angle between ultrasound (US) line and blood flow requires a manual adjustment. Establishing this parameter is critical in order to calculate blood velocity. However, the operator dependency gives high variable results. It is worth noting that a new class of vector Doppler devices can enhance the accuracy and precision of measurements. Such technology uses a double US line that leads to automatically know the Doppler angle. By comparing in an in vitro model of venous flow conventional echo color Doppler (ECD) equipment with the new device, we found a better minimal difference between the latter and the nominal flow rate (20%). On the contrary, the comparison with conventional ECD showed a difference ranging between 2% and 43%, according to the possible settings of the equipment. Our study demonstrates a better accuracy of the experimental device with respect to conventional ECD in measuring the venous flow rate

Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L’)2] × 2H2O (L’ = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent

Disentangling the initiation from the response in joint attention: An eye-tracking study in toddlers with autism spectrum disorders

Joint attention (JA), whose deficit is an early risk marker for autism spectrum disorder (ASD), has two dimensions: (1) responding to JA and (2) initiating JA. Eye-tracking technology has largely been used to investigate responding JA, but rarely to study initiating JA especially in young children with ASD. The aim of this study was to describe the differences in the visual patterns of toddlers with ASD and those with typical development (TD) during both responding JA and initiating JA tasks. Eye-tracking technology was used to monitor the gaze of 17 children with ASD and 15 age-matched children with TD during the presentation of short video sequences involving one responding JA and two initiating JA tasks (initiating JA-1 and initiating JA-2). Gaze accuracy, transitions and fixations were analyzed. No differences were found in the responding JA task between children with ASD and those with TD, whereas, in the initiating JA tasks, different patterns of fixation and transitions were shown between the groups. These results suggest that children with ASD and those with TD show different visual patterns when they are expected to initiate joint attention but not when they respond to joint attention. We hypothesized that differences in transitions and fixations are linked to ASD impairments in visual disengagement from face, in global scanning of the scene and in the ability to anticipate object's action

What's in a Name? Shifting Identities of Traditional Organized Crime in Canada in the Transnational Fight against the Calabrian ‘Ndrangheta

The Italian antimafia authorities have warned Canadian law enforcement about the risks and the growing concerns for the infiltration of clans of the Calabrian mafia, known as ‘ndrangheta, in Eastern Canada. The alarm linked to the rise of the ‘ndrangheta challenges the paradigms of traditional organized crime in Canada, because the ‘ndrangheta is presented as traditional but also innovative and more pervasive than other mafia-type groups. Through access to confidential investigations and interviews to key specialist law enforcement teams in Toronto and Montreal, this article investigates today's institutional perception of mafia – the ‘ndrangheta in particular – in Canada when compared to Italian conceptualizations. I will argue that the changes in narratives in Canada can be read in relation to changes in the Italian identity in the country, moving towards regionalization and specialist knowledge of ethnic differences

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders

Motor Skills as Moderators of Core Symptoms in Autism Spectrum Disorders: Preliminary Data From an Exploratory Analysis With Artificial Neural Networks

Motor disturbances have been widely observed in children with autism spectrum disorder (ASD), and motor problems are currently reported as associated features supporting the diagnosis of ASD in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Studies on this issue reported disturbances in different motor domains, including both gross and fine motor areas as well as coordination, postural control, and standing balance. However, they failed to clearly state whether motor impairments are related to demographical and developmental features of ASD. Both the different methodological approaches assessing motor skills and the heterogeneity in clinical features of participants analyzed have been implicated as contributors to variance in findings. However, the non-linearity of the relationships between variables may account for the inability of the traditional analysis to grasp the core problem suggesting that the “single symptom approach analysis” should be overcome. Artificial neural networks (ANNs) are computational adaptive systems inspired by the functioning processes of the human brain particularly adapted to solving non-linear problems. This study aimed to apply the ANNs to reveal the entire spectrum of the relationship between motor skills and clinical variables. Thirty-two male children with ASD [mean age: 48.5 months (SD: 8.8); age range: 30–60 months] were recruited in a tertiary care university hospital. A multidisciplinary comprehensive diagnostic evaluation was associated with a standardized assessment battery for motor skills, the Peabody Developmental Motor Scale-Second Edition. Exploratory analyses were performed through the ANNs. The findings revealed that poor motor skills were a common clinical feature of preschoolers with ASD, relating both to the high level of repetitive behaviors and to the low level of expressive language. Moreover, unobvious trends among motor, cognitive and social skills have been detected. In conclusion, motor abnormalities in preschoolers with ASD were widespread, and the degree of impairment may inform clinicians about the severity of ASD core symptoms. Understanding motor disturbances in children with ASD may be relevant to clarify neurobiological basis and ultimately to guide the development of tailored treatments