Autism spectrum disorder (ASD) is a common comorbidity of epilepsy and seizures and/or epileptiform activity are observed in a significant proportion of ASD patients. Current research also implies that autistic traits can be observed to a various degree in mice and rats with seizures. This suggests that there are shared mechanisms in both ASD and epilepsy syndromes. Here, we first review the standard, validated methods used to assess autistic traits in animal models as well as their limitations with regards to epilepsy models. We then discuss two of the potential pathological processes that could be shared between ASD and epilepsy. We first focus on functional implications of neuroinflammation including changes to excitable networks mediated by inflammatory regulators. Finally we examine mechanisms at the cellular and network level involved in neuronal excitability, timing and network coordination that may directly lead to behavioral disturbances present in both epilepsy and ASD. This mini-review summarizes the work first presented at an Investigators Workshop at the 2016 American Epilepsy Society meeting.

The real impact of reactive oxygen species, antioxidant enzymes, mitochondrial dysfunction and chronic inflammation on the development of autism spectrum disorders (ASD) remains unclear, and even controversial. In this study we compared the plasma levels of antioxidant enzymes and their cofactors, markers of oxidative damage, and the respiratory burst in peripheral blood polymorphonuclear leukocytes (PMNL) as surrogate marker of chronic inflammation obtained from 10 children (4-10 year old) who met DSM-5 criteria and their siblings. We demonstrated diminished superoxide dismutase (SOD) and enhanced catalase (CAT) activities resulting in a markedly decreased SOD/CAT ratio and enhanced carbonyl content in the plasma of ASD patients. A strong correlation was present between SOD and CAT activities in the control group, which was not noted in ASD patients. Moreover, in autistic patients, we observed negative correlation between SOD activity on one side, and carbonyl content in plasma, 8-Hydroxy-2-deoxyguanosin content in urine, and respiratory burst intensity in PMNL on the other side. At the same time, low SOD level in autistic children was positively correlated with the magnesium content in the packed RBCs, which might indicate the involvement of the mitochondrial MnSOD in ASD pathogenesis, and therefore the consequent partaking of mitochondrial dysfunction in the development of ASD. Altogether, these results indicate that decreased antioxidant capacity and increased oxidative stress in ASD patients may have functional consequence in terms of increased superoxide leakage, oxidative protein damage, chronic inflammatory response, and, finally, neuronal cell abnormal functioning or death.

Data from children with ASD who are learning Indo-European languages indicate that (a) they vary hugely in their expressive language skills and (b) their pragmatic/socially-based language is more impaired than their structural language. We investigate whether similar patterns of language development exist for Mandarin-exposed children with ASD. Parent report data of the Putonghua Communicative Development Inventory-Toddler Form were collected from 160 17-83-month-old children with ASD. These children with ASD demonstrated similar levels of variability as Western children with ASD. In particular, they could be divided into three distinct subgroups (high verbal, middle verbal, low verbal), all of which manifested relative strengths in lexical and grammatical language compared to pragmatic usage of decontextualized language.

Vitamin C deficiency is anecdotal in developed countries, mainly associated with underling clinical morbidities as autism or neurological impairment. Chronic insufficient dietary supply is responsible for vascular fragility and impaired bone formation, resulting in gingival bleeding, petechial lesions, articular and bone pain or limb swelling. Children may present anorexia, irritability, failure to thrive, limping or refusal to walk. Accordingly, pediatric scurvy is frequently misdiagnosed with osteomyelitis, septic arthritis, bone and soft tissue tumor, leukemia, bleeding disorders, and rheumatologic conditions. We report the case of a 3-years old child developing scurvy as consequence of strict selective diet; extensive and invasive investigations were undertaken before the correct diagnosis was considered. Despite being considered a rare condition, scurvy still exists nowadays, even in children with no apparent risk factors living in wealthy families. The increasing popularity of dietary restriction for children, especially those with allergies, may potentially enhance the occurrence of scurvy in apparently healthy children. Appropriate dietary anamnesis is fundamental in order to highlight potential nutritional deficit and to avoid unnecessary invasive diagnostic procedures. Patients without considerable risk factors may benefit from psychological support in order to investigate possible eating disorders.

The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies. Opinions on the initial failures of DBS trials for some psychiatric diseases point to a certain lack of finesse in using an Open Loop DBS (OLDBS) system in these dynamic, cyclical pathologies. OLDBS delivers monomorphic input into dysfunctional brain circuits with modulation of that input via human interface at discrete time points with no interim modulation or adaptation to the changing circuit dynamics. Closed Loop DBS (CLDBS) promises dynamic, intrinsic circuit modulation based on individual physiologic biomarkers of dysfunction. Discussed here are several psychiatric diseases which may be amenable to CLDBS paradigms as the neurophysiologic dysfunction is stochastic and not static. Post-Traumatic Stress Disorder (PTSD) has several peripheral and central physiologic and neurologic changes preceding stereotyped hyper-activation behavioral responses. Biomarkers for CLDBS potentially include skin conductance changes indicating changes in the sympathetic nervous system, changes in serum and central neurotransmitter concentrations, and limbic circuit activation. Chemical dependency and addiction have been demonstrated to be improved with both ablation and DBS of the Nucleus Accumbens and as a serendipitous side effect of movement disorder treatment. Potential peripheral biomarkers are similar to those proposed for PTSD with possible use of environmental and geolocation based cues, peripheral signs of physiologic arousal, and individual changes in central circuit patterns. Non-substance addiction disorders have also been serendipitously treated in patients with OLDBS for movement disorders. As more is learned about these behavioral addictions, DBS targets and effectors will be identified. Finally, discussed is the use of facial recognition software to modulate activation of inappropriate responses for psychiatric diseases in which misinterpretation of social cues feature prominently. These include Autism Spectrum Disorder, PTSD, and Schizophrenia-all of which have a common feature of dysfunctional interpretation of facial affective clues. Technological advances and improvements in circuit-based, individual-specific, real-time adaptable modulation, forecast functional neurosurgery treatments for heretofore treatment-resistant behavioral diseases.

Adults diagnosed with autism are at significantly increased risk of suicidal thoughts, suicidal behaviours and dying by suicide. However, it is unclear whether any validated tools are currently available to effectively assess suicidality in autistic adults in research and clinical practice. This is crucial for understanding and preventing premature death by suicide in this vulnerable group. This two stage systematic review therefore aimed to identify tools used to assess suicidality in autistic and general population adults, evaluate these tools for their appropriateness and measurement properties, and make recommendations for appropriate selection of suicidality assessment tools in research and clinical practice. Three databases were searched (PsycInfo, Medline and Web of Knowledge). Four frequently used suicidality assessment tools were identified, and subsequently rated for quality of the evidence in support of their measurement properties using the COSMIN checklist. Despite studies having explored suicidality in autistic adults, none had utilised a validated tool. Overall, there was lack of evidence in support of suicidality risk assessments successfully predicting future suicide attempts. We recommend adaptations to current suicidality assessment tools and priorities for future research, in order to better conceptualise suicidality and its measurement in autism.

There is a growing research interest on the antenatal features of children with neurodevelopmental disorders. Indeed, it has been proved that the neurodevelopment is, at least partly, affected by processes occurring in fetal life and that the early neurodevelopmental disorders identification is essential to optimize long-term outcomes. This systematic review aims to summarize findings on antenatal ultrasound data, which are or might be considered early risk indexes of postnatal social impairments. We conducted systematic searches in Pubmed and PsychINFO databases to identify studies including fetal ultrasound measurements and postnatal neurodevelopmental outcome assessment. The bibliographic search included 3203 articles but after the assessment of the eligibility conducted by two independent researchers, only 26 studies were selected. Some alterations in ultrasound antenatal measurements (such as biophysical data, nuchal thickness and enlargement of cerebral ventricles) have been associated to autism spectrum disorder. However, data are still limited, controversial and not specific. Reported data are here discussed to strongly support studies on fetuses at high risk for autism spectrum disorder.