Feeding-Related Early Signs of Autism Spectrum Disorder: A Narrative Review.

Feeding difficulties are prevalent among individuals with autism spectrum disorder (ASD). Nevertheless, the knowledge about the association between feeding-related early signs and child development remains limited. This review aimed to describe the signs and symptoms related to feeding during child development and to explore their relevance to the diagnosis of ASD. Specialists in nutrition and/or ASD conducted a search of MEDLINE, PsycINFO, and Web of Science databases. Although studies in typically developing children demonstrate age-related variations in hunger and satiety cues, the literature about early feeding indicators in ASD is scarce. Challenges such as shortened breastfeeding duration, difficulties in introducing solid foods, and atypical mealtime behaviors are frequently observed in children with ASD. The eating difficulties experienced during childhood raise concerns for caregivers who base their feeding practices on their perceptions of food acceptance or refusal. Considering the observed associations between feeding difficulties and ASD, the importance of recognizing feeding-related signs according to developmental milestones is emphasized to alert medical professionals that deviation in the formation of feeding habits and skills could indicate the need for ASD diagnostic investigation.

Revisiting the history of autism before Kanner and Asperger: a tribute to Grunya Sukhareva.

Almost two decades before Kanner's and Asperger's works, the original paper by child psychiatrist Grunya Efimovna Sukhareva had already been written. It was published in 1926 by Sukhareva in a German scientific journal of psychiatry and neurology, with a detailed description of children who presented clinical conditions whose characteristics and evolution closely resemble autism, according to current criteria. In the present historical note, we intend to present Sukhareva's pioneering work and retrieve the meaning of her original contribution.

Quase duas décadas antes dos trabalhos de Kanner e Asperger, o artigo original da psiquiatra infantil Grunya Efimovna Sukhareva já havia sido escrito. Foi publicado por Sukhareva em 1926, em uma revista científica alemã de psiquiatria e neurologia, com uma descrição detalhada de crianças que apresentavam quadro clínico cujas características e evolução em muito se assemelham ao autismo, segundo os critérios atuais. Nesta nota histórica, pretende-se apresentar o trabalho pioneiro de Sukhareva e resgatar o significado da sua contribuição original.

Normative values to Horus® computerized posturography in children. / Valores normativos para a posturografia computadorizada Horus® em crianças.

PURPOSE: Propose normalization values of the Horus® computerized posturography platform, in children aged 4 to 6 years, without auditory and/or vestibular complaints. METHODS: Cross-sectional study, 216 children aged 4 to 6 years participated. All the children underwent to visual screening, audiological evaluation and computerized posturography, which consists of research on stability limits and seven sensory conditions. The results were statistically analyzed using the tests non-parametric Kruskal-Walli, post hoc Dunn-Bonferroni for pairwise age comparisons and the Mann-Whitney U for sex analysis. Categorical data were presented in relative frequency and quantitative data in mean and standard deviation. RESULTS: Standardization values were described for the stability limit and for the seven sensory conditions. There was a difference for the stability limit between sex at 4 years old(p<0.007) and, in the comparison between ages 4 and 5 (p=0.005) and 4 and 6 years old(p<0.001). In the residual functional balance, comparison between ages, there was a difference between 4 and 5, 4 and 6, 5 and 6 years, however for different data. The presence of statistical difference for different evaluation data also occurred in the analysis by sex. In the sensory systems, the findings between ages showed differences for the vestibular system, right and left optokinetic visual dependence, tunnel visual dependence and for the composite balance index. CONCLUSION: It was possible to establish normative values for the Horus® posturography in healthy children aged 4 to 6 years.

OBJETIVO: Propor valores de normatização da plataforma de posturografia computadorizada Horus®, em crianças de 4 a 6 anos, sem queixas auditivas e/ou vestibulares. MÉTODO: Estudo transversal. Participaram 216 crianças na faixa etária de 4 a 6 anos. Todas realizaram triagem visual, avaliação auditiva e posturografia computadorizada composta por pesquisa do limite de estabilidade e sete condições sensoriais. Analisaram-se os resultados estatisticamente por testes não paramétrico Kruskal-Walli, post hoc Dunn-Bonferroni para comparações par-a-par nas idades e U de Mann-Whitney para análise entre sexo. Os dados categóricos foram apresentados em frequência relativa e os dados quantitativos pela média e desvio padrão. RESULTADOS: Foram descritos valores de normatização para o limite de estabilidade e para as sete condições sensoriais. Houve diferença para o limite de estabilidade entre sexos aos 4 anos (p<0,007) e, na comparação entre as idades 4 e 5 anos (p=0,005) e 4 e 6 anos (p<0,001). No equilíbrio funcional residual, comparação entre idades, houve diferença entre 4 e 5, 4 e 6 e, 5 e 6 anos, entretanto para diferentes dados. A presença de diferença estatística para diferentes dados da avaliação, ocorreu também na análise por sexo. Nos sistemas sensoriais os achados entre idades mostraram diferença para o sistema vestibular, dependência visual optocinética direita e esquerda, dependência visual túnel e para índice de equilíbrio composto. Sugere-se que para esta população, as respostas na posturografia sejam analisadas por faixa etária e sexo. CONCLUSÃO: Foi possível estabelecer valores normativos para a posturografia Horus® em crianças hígidas na faixa etária de 4 a 6 anos.

Folic acid and autism: updated evidences.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication 'Folic acid and autism: What do we know?' and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs.

Revisiting the history of autism before Kanner and Asperger: a tribute to Grunya Sukhareva / Revisitando a história do autismo antes de Kanner e Asperger: um tributo a Grunya Sukhareva

Abstract Almost two decades before Kanner's and Asperger's works, the original paper by child psychiatrist Grunya Efimovna Sukhareva had already been written. It was published in 1926 by Sukhareva in a German scientific journal of psychiatry and neurology, with a detailed description of children who presented clinical conditions whose characteristics and evolution closely resemble autism, according to current criteria. In the present historical note, we intend to present Sukhareva's pioneering work and retrieve the meaning of her original contribution.

Resumo Quase duas décadas antes dos trabalhos de Kanner e Asperger, o artigo original da psiquiatra infantil Grunya Efimovna Sukhareva já havia sido escrito. Foi publicado por Sukhareva em 1926, em uma revista científica alemã de psiquiatria e neurologia, com uma descrição detalhada de crianças que apresentavam quadro clínico cujas características e evolução em muito se assemelham ao autismo, segundo os critérios atuais. Nesta nota histórica, pretende-se apresentar o trabalho pioneiro de Sukhareva e resgatar o significado da sua contribuição original.

Stroke in children and adolescents: Analysis of electrophysiological and behavioral assessment findings of auditory processing.

PURPOSE: This study aimed to analyze the auditory processing behavior of children and adolescents diagnosed with stroke and compare it with that of typically developing individuals. METHODS: This was an analytical cross-sectional study involving 48 participants aged between 7 and 17 years with adequate schooling for age and grade, allocated equally to two groups: Stroke (SG) and Control Groups (CG). For the SG, cases identified between 2003 and 2018 were considered. In the CG, school-aged participants with typical development were randomized. After screening for differential audiological assessment and confirmation of auditory pathway integrity at the brainstem level, binaural analyses of the auditory processing behavior were conducted using the Dichotic Digit Test (DDT), Frequency Pattern Test (FPT), and electrophysiological assessment (P300). The Shapiro-Wilk test for normality was conducted, followed by the T and Mann-Whitney tests, with a 95 % confidence level and significance offset at p < 0.05, using the SPSS software (IBM®, v. 22.) RESULTS: The CG performed better in terms of auditory processing. These differences were significant (p < 0.0001) for the binaural integration of DDT, FPT humming and Labeling, and P300 latency. The P300 results were similar; however, with a greater amplitude in the SG. CONCLUSION: This study showed that children and adolescents with stroke performed worse in electrophysiological and behavioral tests of auditory processing assessed using the auditory evoked potentials. These data reinforce the hypothesis that stroke-related lesions compromise the neural mechanisms underlying auditory processing.

Preventive effects of resveratrol against early-life impairments in the animal model of autism induced by valproic acid.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive/stereotyped behaviors. Its prevalence is increasing, affecting one in 36 children in the United States. The valproic acid (VPA) induced animal model of ASD is a reliable method for investigating cellular, molecular, and behavioral aspects related to the disorder. Trans-Resveratrol (RSV), a polyphenol with anti-inflammatory and antioxidant effects studied in various diseases, has recently demonstrated the ability to prevent cellular, molecular, sensory, and social deficits in the VPA model. In this study, we examined the effects of prenatal exposure to VPA and the potential preventive effects of RSV on the offspring. Method: We monitored gestational weight from embryonic day 6.5 until 18.5 and assessed the onset of developmental milestones and morphometric parameters in litters. The generalized estimating equations (GEE) were used to analyze longitudinal data. Results: Exposure to VPA during rat pregnancy resulted in abnormal weight gain fold-changes on embryonic days 13.5 and 18.5, followed by fewer animals per litter. Additionally, we discovered a positive correlation between weight variation during E15.5-E18.5 and the number of rat pups in the VPA group. Conclusion: VPA exposure led to slight length deficiencies and delays in the onset of developmental milestones. Interestingly, the prenatal RSV treatment not only prevented most of these delays but also led to the early onset of certain milestones and improved morphometric characteristics in the offspring. In summary, our findings suggest that RSV may have potential as a therapeutic intervention to protect against the negative effects of prenatal VPA exposure, highlighting its importance in future studies of prenatal neurodevelopmental disorders.

HLA-G*14 bp indel variant in autism spectrum disorder in a population from southern Brazil.

Altered immune response during pregnancy has been associated with ASD susceptibility. HLA-G is expressed by the trophoblast at the maternal/fetal interface and induces allogenic tolerance toward the fetus. A 14-bp insertion in the HLA-G 3'UTR (rs371194629) was associated with reduced levels of HLA-G. We aimed to assess the influence of the HLA-G*14 bp indel variant in ASD susceptibility and symptomatology in a Brazilian admixed sample. The insertion genotype (14 bp+/14 bp+) was firstly associated with hetero aggression, but statistical significance was lost after correction (p = 0.035, pcorrected = 0.35). No association between the HLA-G variant and susceptibility to ASD or differential clinical manifestations were observed.

Exploring potential impacts of pregnancy-related maternal immune activation and extracellular vesicles on immune alterations observed in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders usually observed in early life, with impacts on behavioral and social skills. Incidence of ASD has been dramatically increasing worldwide, possibly due to increase in awareness/diagnosis as well as to genetic and environmental triggers. Currently, it is estimated that ∼1% of the world population presents ASD symptoms. In addition to its genetic background, environmental and immune-related factors also influence the ASD etiology. In this context, maternal immune activation (MIA) has recently been suggested as a component potentially involved in ASD development. In addition, extracellular vesicles (EVs) are abundant at the maternal-fetal interface and are actively involved in the immunoregulation required for a healthy pregnancy. Considering that alterations in concentration and content of EVs have also been associated with ASD, this article raises a debate about the potential roles of EVs in the processes surrounding MIA. This represents the major differential of the present review compared to other ASD studies. To support the suggested correlations and hypotheses, findings regarding the roles of EVs during pregnancy and potential influences on ASD are discussed, along with a review and update concerning the participation of infections, cytokine unbalances, overweight and obesity, maternal anti-fetal brain antibodies, maternal fever, gestational diabetes, preeclampsia, labor type and microbiota unbalances in MIA and ASD.

Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders mainly characterized by repetitive, restrictive and stereotypical behaviors, and impaired communication skills. Several lines of evidence indicate that alterations of the immune system account for ASD development, including the presence of brain-reactive antibodies, abnormal T cell activation, altered cytokine levels in brain, cerebrospinal fluid and peripheral blood circulation, increased levels of circulating monocytes, and dysregulation in Natural Killer (NK) cells activity. Regarding NK cells, a lower cytotoxic activity, a higher level of activation and an increased number of these cells in individuals with ASD have been described. In 2019, a study showed that NK cells derived from patients with ASD show a characteristic pattern of NKG2C overexpression, highlighting the importance of the NK cell pathway in ASD. In fact, the study of genes related to NK cell activity has proven to be an excellent research target, both in terms of susceptibility as well as a marker for the different clinical manifestations observed in ASD individuals. Here, we evaluated the influence of KLRC2 gene deletion as well as KLRK1 rs1049174 and rs2255336 variants in a cohort of 185 children diagnosed with ASD and their respective biological parents in southern Brazil. Of note, this is the first study concerning genetic variants of the KLRC2 and KLRK1 genes in an ASD sample. The KLRC2 gene deletion (p = 0.001; pc = 0.009), KLRK1 rs1049174 (p = 0.005; pc = 0.045) and KLRK1 rs2255336 (p = 0.001; pc = 0.009) were associated with epilepsy in ASD patients. The results indicate that KLRC2 deletion, KLRK1 rs2255336, and KLRK1 rs1049174 could be involved in epilepsy manifestation in ASD patients, possibly impacting the NK dysregulation already described in ASD and epileptic patients.

Mismatch Negativity in Children and Adolescents with Autism Spectrum Disorder

Abstract Introduction Individuals with autism spectrum disorder (ASD) have abnormalities in auditory perception and sensitivity. The mismatch negativity (MMN) component of the evoked potential demonstrates a brain detection response to an auditory change due to memory, and enables the identification of changes in the auditory system. Objectives To analyze MMN responses in children and adolescents with ASD and compare them with those of a control group. Methods Cross-sectional and comparative study. The sample was composed of 68 children and adolescents, divided into study group (SG), which contained those diagnosed with ASD, and the control group (CG), which contained those with typical development, normal hearing thresholds, and without hearing complaints. All participants were submitted to peripheral and central electrophysiological auditory evaluations. For the electrophysiological auditory evaluation and MMN recording, the electrodes were fixed in the following positions: Fz (active electrode), M1 and M2 (reference electrodes), and on the forehead (ground electrode). Auditory stimuli were presented in both ears simultaneously, with a frequency of 1,000 Hz for the frequent stimulus, and of 2,000 Hz for the rare stimulus, in an intensity of 80 dBNA. Results Latency and amplitude values were increased in the SG, with a statistically significant difference in comparison with the CG. In the MMN analysis, there was no statistically significant difference in the comparison between right and left ears and between genders. Conclusions Children and adolescents with ASD had higher latency and amplitude values in the MMN component than the individuals in the CG.

Mismatch Negativity in Children and Adolescents with Autism Spectrum Disorder.

Introduction Individuals with autism spectrum disorder (ASD) have abnormalities in auditory perception and sensitivity. The mismatch negativity (MMN) component of the evoked potential demonstrates a brain detection response to an auditory change due to memory, and enables the identification of changes in the auditory system. Objective To analyze MMN responses in children and adolescents with ASD and compare them with those of a control group. Methods Cross-sectional and comparative study. The sample was composed of 68 children and adolescents, divided into study group (SG), which contained those diagnosed with ASD, and the control group (CG), which contained those with typical development, normal hearing thresholds, and without hearing complaints. All participants were submitted to peripheral and central electrophysiological auditory evaluations. For the electrophysiological auditory evaluation and MMN recording, the electrodes were fixed in the following positions: Fz (active electrode), M1 and M2 (reference electrodes), and on the forehead (ground electrode). Auditory stimuli were presented in both ears simultaneously, with a frequency of 1,000 Hz for the frequent stimulus, and of 2,000 Hz for the rare stimulus, in an intensity of 80 dBNA. Results Latency and amplitude values were increased in the SG, with a statistically significant difference in comparison with the CG. In the MMN analysis, there was no statistically significant difference in the comparison between right and left ears and between genders. Conclusion Children and adolescents with ASD had higher latency and amplitude values in the MMN component than the individuals in the CG.

Stroke in children and adolescents: Analysis of electrophysiological and behavioral assessment findings of auditory processing

Abstract Purpose: This study aimed to analyze the auditory processing behavior of children and adolescents diagnosed with stroke and compare it with that of typically developing individuals. Methods: This was an analytical cross-sectional study involving 48 participants aged between 7 and 17 years with adequate schooling for age and grade, allocated equally to two groups: Stroke (SG) and Control Groups (CG). For the SG, cases identified between 2003 and 2018 were considered. In the CG, school-aged participants with typical development were randomized. After screening for differential audiological assessment and confirmation of auditory pathway integrity at the brainstem level, binaural analyses of the auditory processing behavior were conducted using the Dichotic Digit Test (DDT), Frequency Pattern Test (FPT), and electrophysiological assessment (P300). The Shapiro-Wilk test for normality was conducted, followed by the T and Mann-Whitney tests, with a 95 % confidence level and significance offset at p < 0.05, using the SPSS software (IBM®, v. 22.) Results: The CG performed better in terms of auditory processing. These differences were significant (p < 0.0001) for the binaural integration of DDT, FPT humming and Labeling, and P300 latency. The P300 results were similar; however, with a greater amplitude in the SG. Conclusion: This study showed that children and adolescents with stroke performed worse in electrophysiological and behavioral tests of auditory processing assessed using the auditory evoked potentials. These data reinforce the hypothesis that stroke-related lesions compromise the neural mechanisms underlying auditory processing.

The effect of the "K" technique on levels of anxiety and salivar cortisol in adolescents / O efeito da técnica "K" nos níveis de ansiedade e cortisol salivar em adolescentes / El efecto de la técnica "K" sobre la ansiedad y los niveles de cortisol salivales en adolescentes

This research presents theoretical arguments of a new approach called Technique "K," which aims to reduce student's anxiety before a cognitive challenge. Through a randomized, controlled clinical trial, we evaluate the Beck Anxiety Inventory and salivary cortisol. We compared the results in the last year of high school, who were facing school tests, before and after the application of the "K" technique (intervention group) and placebo (control group). Statistical analyses consisted of using the Chisquare, Spearman and the Wilcoxon test. The principal component analysis observed in the case group, - 10.50 (-18.25; -4.75), was statistically higher than the control group, -6.00 (-8.75; -1.25). It is not possible to identify statistical significance (p = 0.462) in the variation of salivary cortisol concentration. The results suggest the effectiveness of the "K" technique in managing anxiety in high school students. Although, future research is needed to extend the preliminary data obtained in this study

Esta pesquisa apresenta argumentos teóricos de uma nova abordagem denominada Técnica "K", visando reduzir a ansiedade do aluno diante de um desafio cognitivo. Por meio de um ensaio clínico randomizado e controlado, avaliamos o Inventário de Ansiedade de Beck e o cortisol salivar. Comparamos os resultados dos alunos, que estavam enfrentando provas escolares, antes e após a aplicação da técnica "K" (grupo intervenção) e placebo (grupo controle). As análises estatísticas consistiram na utilização do Qui-quadrado, Spearman e teste de Wilcoxon. A análise de componentes principais observada no grupo caso, -10,50 (-18,25; -4,75), foi estatisticamente superior ao grupo controle, -6,00 (-8,75; -1,25). Não é possível identificar significância estatística (p = 0,462) na variação da concentração de cortisol salivar. Os resultados sugerem a eficácia da técnica "K" no manejo da ansiedade em estudantes do ensino médio. No entanto, pesquisas futuras são necessárias para estender os dados preliminares obtidos neste estudo

Esta investigación presenta argumentos teóricos para un nuevo enfoque denominado Técnica "K", con el objetivo de reducir la ansiedad de los estudiantes frente a un desafío cognitivo. A través de un ensayo clínico aleatorizado y controlado, evaluamos el Inventario de Ansiedad de Beck y el cortisol salival. Comparamos los resultados de los estudiantes, que se enfrentaban a pruebas escolares, antes y después de la aplicación de la técnica "K" (grupo de intervención) y placebo (grupo control). Los análisis estadísticos consistieron en utilizar la prueba de Chicuadrado, Spearman y Wilcoxon. El análisis de componentes principales observado en el grupo de casos, -10,50 (-18,25; -4,75), fue estadísticamente superior al grupo control, -6,00 (-8,75; -1,25). No es posible identificar significación estadística (p = 0,462) en la variación de la concentración de cortisol salival. Los resultados sugieren la efectividad de la técnica "K" en el manejo de la ansiedad en estudiantes de secundaria. Sin embargo, se necesitan futuras investigaciones para ampliar los datos preliminares obtenidos en este estudio

Resveratrol Treatment of Autism Spectrum Disorder-A Pilot Study.

OBJECTIVES: Considering autism spectrum disorder (ASD) as a neurodevelopmental condition associated with immune system impairments, we aimed to evaluate the potential benefits, efficacy, tolerability, and safety of the anti-inflammatory, antioxidant, and neuroprotective trans -resveratrol (RSV) in behavioral impairments and in a set of 8 microRNAs (miR) related to the immune system in pediatric subjects with ASD. METHODS: This is an open-label pilot trial over a 3 months (90 days) study follow-up period designed to assess the effect of 200 mg/d RSV on 5 boys aged 10 to 13 (11.8 ± 1.1) years diagnosed with ASD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition . RESULTS: The RSV treatment significantly reduced the Aberrant Behavior Checklist total score ( P = 0.042) and Irritability ( P = 0.041), with no alteration in Stereotypical Behavior ( P = 0.066), Hyperactivity ( P = 0.068), and Lethargy/Social Withdrawal ( P = 0.078) subscales. On the Clinical Global Impression scale, 3 individuals showed marked improvement in behavior; one showed mild improvement, and the other had no changes. The RSV treatment increased the miR-195-5p ( P = 0.043), an important modulator of targets related to inflammatory and immunological pathways. RSV administration did not present adverse effects and did not alter clinical laboratory results. CONCLUSIONS: RSV is a safe molecule for administrating in the pediatric population, able to modulate behavior alterations and molecules associated with the immune system, becoming a promising therapeutic strategy for large-scale studies in ASD, to investigate both behavioral and molecular approaches.

Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.

The role of T-cells in neurobehavioural development: Insights from the immunodeficient nude mice.

Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations.

Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months.

OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.

Resveratrol prevents brain edema, blood-brain barrier permeability, and altered aquaporin profile in autism animal model.

Autism spectrum disorder can present a plethora of clinical conditions associated with the disorder, such as greater brain volume in the first years of life in a significant percentage of patients. We aimed to evaluate the brain water content, the blood-brain barrier permeability, and the expression of aquaporin 1 and 4, and GFAP in a valproic acid-animal model, assessing the effect of resveratrol. On postnatal day 30, Wistar rats of the valproic acid group showed greater permeability of the blood-brain barrier to the Evans blue dye and a higher proportion of brain water volume, prevented both by resveratrol. Prenatal exposition to valproic acid diminished aquaporin 1 in the choroid plexus, in the primary somatosensory area, in the amygdala region, and in the medial prefrontal cortex, reduced aquaporin 4 in medial prefrontal cortex and increased aquaporin 4 levels in primary somatosensory area (with resveratrol prevention). Valproic acid exposition also increased the number of astrocytes and GFAP fluorescence in both primary somatosensory area and medial prefrontal cortex. In medial prefrontal cortex, resveratrol prevented the increased fluorescence. Finally, there was an effect of resveratrol per se on the number of astrocytes and GFAP fluorescence in the amygdala region and in the hippocampus. Thus, this work demonstrates significant changes in blood-brain barrier permeability, edema formation, distribution of aquaporin 1 and 4, in addition to astrocytes profile in the animal model of autism, as well as the use of resveratrol as a tool to investigate the mechanisms involved in the pathophysiology of autism spectrum disorder.

Zika Virus Infection Associated with Autism Spectrum Disorder: A Case Report.

INTRODUCTION: The aim of this case was to investigate the association of the Zika virus infection in utero with the autism spectrum disorder (ASD) as clinical outcome that presented no congenital anomalies. METHODS: ASD was diagnosed in the second year of life by different child neurologists and confirmed by DSM-5 and ASQ. After that, an extensive clinical, epidemiological, and genetic evaluations were performed, with main known ASD causes ruled out. RESULTS: An extensive laboratorial search was done, with normal findings. SNP array identified no pathogenic variants. Normal neuroimaging and EEG findings were also obtained. ZIKV (Zika virus) IgG was positive, while IgM was negative. Other congenital infections were negative. The exome sequencing did not reveal any pathogenic variant in genes related to ASD. CONCLUSION: Accordingly, this report firstly associates ZIKV exposure to ASD.