The prenatal use of agmatine prevents social behavior deficits in VPA-exposed mice by activating the ERK/CREB/BDNF signaling pathway.

BACKGROUND: According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid. METHODS: In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring. RESULTS: The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. CONCLUSION: Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 and TSC2 genes, causing overactivation of the mechanistic (previously referred to as mammalian) target of rapamycin (mTOR) signaling pathway in fetal life. The mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy, intellectual disability, and autism spectrum disorder (ASD). Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic infants. DATA SOURCES: We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms "tuberous sclerosis", "autism", or "autism spectrum disorder"," animal models", "preclinical studies", "neurobiology", and "treatment". RESULTS: Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor, visual and social communication skills in the first year of life delays. Reliable genetic, cellular, electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and epilepsy. CONCLUSIONS: Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC.

The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy.

RATIONALE: Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD). The potential efficacy of metformin in preventing and/or controlling ASD behavioral deficits was also recently reported. Suppression of hippocampus autophagy was suggested as a potential pathologic mechanism in ASD. OBJECTIVES: Is metformin's ability to improve ASD clinical phenotype driven by its autophagy-enhancing properties? And does hippocampus autophagy enhancement underlie risperidone's efficacy as well? Both questions are yet to be answered. METHODS: The effectiveness of metformin on alleviation of ASD-like behavioral deficits in adolescent rats exposed prenatally to valproic acid (VPA) was compared to that of risperidone. The potential modulatory effects of risperidone on hippocampal autophagic activity were also assessed and compared to those of metformin. RESULTS: Male offspring exposed to VPA during gestation exhibited marked anxiety, social impairment and aggravation of stereotyped grooming; such deficits were efficiently rescued by postnatal risperidone or metformin therapy. This autistic phenotype was associated with suppressed hippocampal autophagy; as evidenced by reduced gene/dendritic protein expression of LC3B (microtubule-associated proteins 1 light chain 3B) and increased somatic P62 (Sequestosome 1) protein aggregates. Interestingly, compared to risperidone, the effectiveness of metformin in controlling ASD symptoms and improving hippocampal neuronal survival was well correlated to its ability to markedly induce pyramidal neuronal LC3B expression while lowering P62 accumulation. CONCLUSIONS: Our work highlights, for the first time, positive modulation of hippocampus autophagy as potential mechanism underlying improvements in autistic behaviors, observed with metformin, as well as risperidone, therapy.

Elaboração de uma cartilha informativa para familiares e cuidadores de crianças com autismo / Elaboración de un folleto informativo para familiares y cuidadores de niños con autismo / Development of an information booklet for family members and caregivers of children with autism

Objetivo: descrever a elaboração de uma cartilha informativa para familiares e cuidadores de crianças que vivem Transtorno do Espectro Autista. Método: pesquisa metodológica, realizada entre setembro de 2019 a julho de 2022 no sul do Brasil. Resultados: a elaboração envolveu a etapa teórica, validação de conteúdo e construção da cartilha denominada "Crianças autistas**: cartilha para familiares e cuidadores". Composta com seis capítulos: características do transtorno, comportamento da criança, direitos, futuro da criança com autismo e compartilhando experiências e visões. O conteúdo foi validado e para a construção da cartilha foram investigadas as preferências de dispositivos tecnológicos e layout de recursos informativos pelos familiares; após, o protótipo da cartilha passou por teste de usabilidade e navegação, hospedada no Articulate Storyline Software e está disponível para o público-alvo. Considerações finais: o processo de elaboração de recursos educativos para familiares pode auxiliar outros pesquisadores com interesse na área.

Objetivo: describir la elaboración de un folleto informativo para familiares y cuidadores de niños con Trastorno del Espectro Autista. Material y Método: investigación metodológica realizada entre septiembre de 2019 y julio de 2022 en el sur de Brasil. Resultados: la investigación incluyó una etapa teórica, la validación del contenido y la construcción de un folleto llamado "Niños autistas**: folleto para familiares y cuidadores". Consta de seis capítulos: características del trastorno, comportamiento del niño, derechos, futuro de los niños con autismo y compartir experiencias y visiones. Se validó el contenido y, para elaborar el folleto, se investigaron las preferencias de los familiares en cuanto a dispositivos tecnológicos y disposición de los recursos informativos; a continuación, el prototipo de folleto se sometió a pruebas de usabilidad y navegación, se alojó en Articulate Storyline Software y ya está a disposición del público destinatario. Consideraciones finales: el proceso de desarrollo de recursos educativos para familiares puede ayudar a otros investigadores interesados en el área.

Objective: to describe the development of an information booklet for family members and caregivers of children living with Autism Spectrum Disorder. Method: methodological research carried out between September 2019 and July 2022 in southern Brazil. Results: the study involved a theoretical stage, content validation and the construction of a booklet called Autistic children**: a booklet for family members and caregivers". It consists of six chapters: characteristics of the disorder, the child's behavior, rights, the future of children with autism and sharing experiences and visions. The content was validated and to build the booklet, family members' preferences for technological devices and the layout of information resources were investigated; afterwards, the prototype of the booklet underwent usability and navigation tests, was hosted on Articulate Storyline Software and is available to the target audience. Final considerations: the process of developing educational resources for family members can help other researchers with an interest in the area.

Maternal treatment with sodium butyrate reduces the development of autism-like traits in mice offspring.

Several studies indicate a relationship between maternal gut microbiota alteration and increased risk of autism spectrum disorders (ASD) in offspring. The possibility of compensating for such metabolic dysfunction at a very early stage of disease via maternal treatment has not been enough explored. Here, we examined in BTBR mouse model of ASD the effect of maternal treatment with the gut microbial metabolite butyrate (BUT) on the behavioral and synaptic plasticity deficits in juvenile and adult offspring. We show that BUT treatment of BTBR dams rescues the social and partially the repetitive behavior deficits in the offspring. In addition, maternal BUT implementation prevents the cerebellar cortex hypertrophy as well as the Purkinje cells firing and long-term synaptic plasticity deficits in BTBR mice. Our results demonstrate, for the first time, that maternal BUT treatment can improve ASD-like symptoms in offspring thus providing new directions for the early treatment of neurodevelopmental disorders.

El Cuestionario de Indicadores de Riesgo de los Trastornos de Espectro Autista durante el Primer Año de Vida (CIRTEA) para la detección precoz / The Risk Indicators Questionnaire for Autism Spectrum Disorders during the First Year of Life (CIRTEA) for early detection

El Cuestionario de Indicadores de Riesgo de los Trastornos de Espectro Autista durante el Primer Año de Vida (CIRTEA) es un instrumento descreening diseñado como una escala de desarrollo prospectiva que usa como referencia los parámetros de desarrollo típicos del menor sin alteraciones para identificar aspectos evolutivos que pudieran están relacionados con el TEA a la edad de 12 meses. El cuestionario fue puesto a pruebaen 955 bebés de 0 a 12 meses (529 niños y 426 niñas) de la provincia de Málaga. La fiabilidad test-retest y la validez externa del cuestionario fueexplorada en una muestra clínica formada por 64 bebés (41 niños, 23 niñas). La versión final está formada por 23 ítems dicotómicos organizadospor trimestres y por áreas de desarrollo referentes a lo sensorial, social y de la comunicación. Se presentan análisis descriptivos de los ítems, asícomo evidencias de su validez de contenido a través de la validación interjueces por medio del Coeficiente V de Aiken e Intervalo de Confianza y lavalidez externa a través de la correlación con el MCHAT/ES a los 12 meses (-.88) y a los 15 meses (-.89). El instrumento es sensible para captar laausencia de conductas normotípicas y de ponerlas en relación con las conductas compatibles con el Trastorno del Espectro del Autismo, mostrando un alto poder predictivo discriminando a los bebés con desarrollo típico y los casos con sospecha de TEA a una temprana edad de 12 meses. (AU)

The Risk Indicators Questionnaire for Autism Spectrum Disorders during the First Year of Life (CIRTEA) for early detection. CIRTEA is a screeninginstrument designed as a developmental scale that uses the typical developmental parameters of the child without alterations as a reference to identify aspects of development that may be related to ASD. The questionnaire was tested in 955 babies from 0 to 12 months (529 boys and 426 girls)in the province of Malaga. The test-retest reliability and external validity of the questionnaire was explored in a clinical sample consisting of 64 infants(41 boys, 23 girls). The definitive version is made up of 23 dichotomous items organized by quarters and by development areas, referring to theperceptual, social and language aspects. Descriptive analyses of the items are presented, as well as evidence of their content validity through interjudgment validation by means of the Aiken V Coefficient and Confidence Interval and the external validity through the correlation with the MCHAT/ES at 12 months (-.88) and at 15 months (-.89). The instrument is sensitive in capturing the absence of normotypic behaviors and relating them tobehaviors compatible with autism spectrum disorder, showing high predictive power for discriminating babies with typical development and caseswith suspected ASD at an early age of 12 months. (AU)

Intervenciones cognitivo-conductuales para reducir conductas autolesivas en niños y jóvenes con TEA: Una revisión sistemática / Cognitive-behavioural interventions to decrease self-injurious behaviours in children and young people with ASD: A Systematic Review

Las conductas autolesivas en niños y jóvenes con Trastorno del Espectro Autista (TEA) entrañan riesgos para su integridad física, afectan a sucalidad de vida, la de sus familias y dificultan su integración en el ámbito escolar y social, integración ya de por sí limitada por las característicaspropias de este tipo de trastornos. Aunque hay pocos estudios sobre autolesiones en esta población, en general se ha visto que, a mayor afectacióny menor nivel cognitivo, las conductas autolesivas son más frecuentes que en casos más leves. El objetivo de este trabajo fue revisar la eficaciade las intervenciones de tipo cognitivo-conductual para la reducción de conductas autolesivas en niños y jóvenes con TEA. Para ello se realizaronbúsquedas en PsycINFO, Scopus y Google Scholar. La revisión incluyó estudios en lengua inglesa o española sobre intervenciones de tipo cognitivo-conductual para reducir conductas autolesivas en niños y jóvenes con TEA; con muestras formadas por personas TEA entre 1 y 30 años quepresentaban conductas autolesivas; y realizados entre 1970 y 2022. De los 228 estudios identificados, solo 7 cumplieron los criterios de inclusión.Los estudios incluidos en la presente revisión incluyeron participantes entre los 3 y los 26 años diagnosticados con TEA y fueron publicados entre1974 y 2015, evidenciando la eficacia de las intervenciones cognitivo-conductuales. Aunque dichos estudios muestran resultados positivos tras lasintervenciones, su número es escaso, por lo que es necesario seguir investigando sobre la eficacia de las intervenciones de carácter cognitivo-conductual para reducir conductas autolesivas en niños y jóvenes con TEA. (AU)

Self-injurious behaviours in children and young people with Autism Spectrum Disorder (ASD) imply risks to their physical integrity and affect their quality of lifeand that of their families. In addition, they hinder their integration into the school and social environments, this being limited by the characteristics ofthis type of disorder. Although there is little information about self-harm in this population, in general it has been seen that the greater the affectationand the lower the cognitive level, the more prevalent self-injurious behaviours are. The aim of this study was to review the efficacy of cognitive-behavioral interventions for the reduction of self-injurious behaviors in children and youth with ASD. For it, we searched PsycINFO, Scopus and GoogleScholar. The review included studies in English or Spanish languages on cognitive-behavioral interventions to reduce self-injurious behaviors inchildren and youth with ASD; with samples consisting of individuals with ASD between 1 and 30 years of age presenting self-injurious behaviors;and conducted between 1970 and 2022. Of the 228 studies identified, only 7 met the inclusion criteria. The included studies included participantsbetween the ages of 3 and 26 years diagnosed with ASD and were published between 1974 and 2015, evidencing the efficacy of cognitive-behavioral interventions. Although these studies show positive post-intervention results, they are scarce in number. Further research is therefore neededon the effectiveness of behavioural and cognitive interventions to reduce self-injurious behaviours in children and young people with ASD. (AU)

Portable HEPA filter air cleaner use during pregnancy and children's autistic behaviors at four years of age: The UGAAR randomized controlled trial.

BACKGROUND: Developmental exposure to airborne particulate matter (PM) may increase children's risk of developing autism spectrum disorder. We quantified the impact of reducing PM exposure during pregnancy on the development of autistic traits in children. We also assessed associations between indoor fine PM (PM2.5) concentrations during pregnancy and autistic traits. METHODS: In this parallel-group randomized controlled trial, we randomized 540 non-smoking pregnant women to receive HEPA filter air cleaners or to a control group, which did not receive air cleaners. We administered the Social Responsiveness Scale (SRS-2) to caregivers when children were a median of 48 months (range: 48 to 51 months). Our primary outcome was the SRS-2 total T-score. We imputed missing data using multiple imputation with chained equations and our primary analysis was by intention to treat. In secondary analyses, we estimated associations between full pregnancy and trimester-specific indoor PM2.5 concentrations and T-scores. RESULTS: We enrolled participants at a median of 11 weeks' gestation. Our analysis included 478 children (233 control, 245 intervention). The intervention reduced average indoor PM2.5 concentrations by 29 % (95 % CI: 21, 37 %). The mean SRS-2 total T-score was 0.5 units lower (95 % CI: -2.5, 1.5) among intervention participants, with evidence of larger benefits for children at the high end of the T-score distribution. An interquartile range (9.6 µg/m3) increase in indoor PM2.5 during pregnancy was associated with 1.8-unit (95 % CI: 0.3, 3.2) increase in mean SRS-2 total T-score. Effect estimates for PM2.5 concentrations by trimester were smaller and confidence intervals spanned no effect. CONCLUSION: Reducing indoor PM during pregnancy had little impact on mean autism-related behavior scores in children. However, indoor PM2.5 concentrations during pregnancy were associated with higher scores. Exposure to particulate matter during pregnancy may influence the development of autistic traits in childhood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01741051.

Prenatal folic acid supplementation and autism spectrum disorder in 3-year-old offspring: the Japan environment and children's study.

OBJECTIVE: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring. METHODS: We used data from the Japan Environment and Children's Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg). RESULTS: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819-1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840-1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921-1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885-1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake. CONCLUSIONS: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

Perinatal supplementation with omega-3 fatty acids corrects the aberrant social and cognitive traits observed in a genetic model of autism based on FMR1 deletion in rats.

Background and objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which no treatments exist. Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most frequent monogenic cause of ASD. Given the lack of pharmacological treatments for ASD, increasing interest is devoted to non-pharmacological approaches, including dietary interventions. Omega-3 polyunsaturated fatty acids (PUFAs) are critical for neurobehavioraldevelopment. This study had two aims: 1. To validatethe recently developed Fmr1-Δexon 8 rat model of FXS; 2. To assess the impact of omega-3 PUFAs dietary supplementation during pregnancy and lactation on the altered behavior displayed by Fmr1-Δexon 8 rats.Methods: Female Fmr1-Δexon 8 and wild-type Sprague-Dawley rats were fed with either an omega-3 PUFAs enriched diet or with an isocaloric control diet during pregnancy and lactation. Behavioral experiments were carried out on the infant (Postnatal days (PNDs) 9 and 13), juvenile (PND 35) and adult (PND 90) male offspring.Results: Fmr1-Δexon 8 pups showed hypolocomotion, reduced ultrasonic vocalizations (USVs) emission and impaired social discrimination compared to wild-type controls. Juvenile and adult Fmr1-Δexon 8 rats showed deficits in the social and cognitive domains, that were counteracted by perinatal omega-3 PUFAs supplementation.Conclusion: Our results support the validity of the Fmr1-Δexon 8 rat model to mimic key autistic-like features and support an important role of omega-3 PUFAs during of neurodevelopment. Although the mechanisms underlying the beneficial effects of omega-3 PUFAs supplementation in ASD needs to be clarified, this dietary intervention holds promise to mitigate core and comorbid autistic features.

How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

Parent-Mediated Interventions for Infants under 24 Months at Risk for Autism Spectrum Disorder: A Systematic Review of Randomized Controlled Trials.

Prodromal symptoms of Autism Spectrum Disorder (ASD) have been detected within the first year of life. This review evaluated evidence from randomized controlled trials (RCTs) of parent-mediated interventions for infants under 24 months who are at risk for ASD. Electronic databases, including grey literature, were searched up till November 2019. Seven RCTs were identified. There was substantial heterogeneity in recruitment, outcome measures and effect size calculations. Interventions did not reduce the risk of later ASD diagnosis and post-intervention effects on infant outcomes were inconsistent, with five studies reporting significant improvements across both treatment and control groups. Moderate level of evidence of intervention effects on parental interaction skills and the small number of RCTs, and significant limitations restrict generalizability across studies.

Breastmilk Feeding during the First 4 to 6 Months of Age and Childhood Disease Burden until 10 Years of Age.

BACKGROUND: Breastfeeding is recommended due to its beneficial effects on human health. However, the effect of breastfeeding on health differs, resulting in various childhood diseases. OBJECTIVE: Our purpose was to investigate the association between breastfeeding at least in the first 4 months and the subsequent development of 15 certainly defined childhood diseases until 10 years of age, the all-cause hospitalization rate and growth at 6-7 years of age. METHODS: Participants included propensity-score matched 188,052 children born between January 2008 and December 2009, who were followed up till 10 years of age. Data were taken from the National Investigation of birth Cohort in Korea study 2008 database. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression. RESULTS: Compared to formula feeding, breastfeeding was associated with decreased risks of febrile convulsion, attention deficit hyperactivity disorder and autism spectrum disorder, pneumonia, acute bronchiolitis, hypertrophic pyloric stenosis, asthma, all-cause hospitalization, overweight/obesity and short stature. Exclusive breastfeeding at 4 to 6 months of age had similar results to exclusive breastfeeding over 6 months of age. CONCLUSIONS: Breastfeeding in early infancy reduces the risk for various childhood diseases, all-cause hospitalization rate, obesity, and short stature during childhood.

Maternal folic acid supplementation prevents autistic behaviors in a rat model induced by prenatal exposure to valproic acid.

Maternal vitamin supplementation has been demonstrated to reduce the risks of a number of neurodevelopmental diseases in children. Autism spectrum disorder (ASD) is a group of neurodevelopment defects with high prevalence but without satisfactory therapy. The present work detected the effects of pregnancy supplementation with folic acid (FA) at different doses on rat models of ASD induced by prenatal exposure to valproic acid (VPA), an anti-epileptic increasing the risk of ASD when administered during pregnancy. The results show that maternal FA supplementation at a high dose (4 mg kg-1) prevented the delay in growth and development, and the deficits in social communicative behaviors and repetitive behaviors, possibly by restoring the increased dendritic spine density and rectifying the over-expression of synaptic proteins associated with excitatory neurons and the lower expression with inhibitory ones. The results provided experimental evidence suggesting a possible role of maternal FA supplementation in preventing ASD.

LF-rTMS ameliorates social dysfunction of FMR1-/- mice via modulating Akt/GSK-3ß signaling.

Autism spectrum disorders (ASD) are a group of neurological disorders which affect approximately 1% of children around the world. Social dysfunction is one of the two core syndromes of ASD, and still lacks effective treatment. Transcranial magnetic stimulation (TMS) is a noninvasive and safe procedure that uses magnetic fields to modulate neural activity. Whether it were effective in modulating social function remains unclear. By using 3-chamber test, ultrasonic vocalization recording and Western-blotting, we demonstrated that FMR1 (fragile X mental retardation protein) mutant mice, a model of ASD, exhibited obvious defects in social preference and ultrasonic communication. In addition, we detected increase of p-Akt (S473) and p-GSK-3ß (S9), and decrease of p-PSD-95 (T19) in the anterior cingulate cortex (ACC) of FMR1-/- mice. Treating FMR1-/- mice with 1 Hz repetitive TMS (rTMS) exerted a long lasting effect in improving both the ultrasonic communication and social preference, as well as restoring the levels of Akt/GSK-3ß activity and spine density in the FMR1-/-ACC. Our data, for the first time, demonstrated a beneficial effect of low frequency rTMS (LF-rTMS) on the social function of FMR1-/- mice and an involvement of Akt/GSK-3ß signaling in this process, indicating LF-rTMS as a potential therapeutic strategy for ASD patients.

[Immunopsychiatry and SARS-CoV-2 pandemic: Links and possible consequences]. / Immuno-psychiatrie et pandémie de SARS-CoV-2 : liens et possibles conséquences.

OBJECTIVE: The SARS-CoV-2 (or COVID-19) pandemic has been propagating since December 2019, inducing a drastic increase in the prevalence of anxious and depressive disorders in the general population. Psychological trauma can partly explain these disorders. However, since psychiatric disorders also have an immuno-inflammatory component, the direct effects of the virus on the host's immune system, with a marked inflammatory response, but also the secondary inflammation to these psychosocial stressors, may cause the apparition or the worsening of psychiatric disorders. We describe here the probable immunopsychiatric consequences of the SARS-CoV-2 pandemic, to delineate possible screening actions and care that could be planned. METHOD: Data from previous pandemics, and existing data on the psychopathological consequences of the SARS-CoV-2 pandemic, allowed us to review the possible immunopsychiatric consequences of the SARS-CoV-2 pandemic, on the gestational environment, with the risk of consecutive neurodevelopmental disorders for the fetus on one hand, on the children and adults directly infected being at increased risks of psychiatric disorders on the other hand. RESULTS: As in previous pandemics, the activation of the immune system due to psychological stress and/or to infection during pregnancy, might lead to an increased risk of neurodevelopmental disorders for the fetus (schizophrenia and autism spectrum disorders). Furthermore, in individuals exposed to psychological trauma and/or infected by the virus, the risk of psychiatric disorders, especially mood disorders, is probably increased. CONCLUSION: In this context, preventive measures and specialized care are necessary. Thus, it is important to propose a close follow-up to the individuals who have been infected by the virus, in order to set up the earliest care possible. Likewise, in pregnant women, screening of mood disorders during the pregnancy or the postpartum period must be facilitated. The follow-up of the babies born during the pandemic must be strengthened to screen and care for possible neurodevelopmental disorders.