Pubmed du 29/01/20

mercredi 29 janvier 2020

1. Bolton TAW, Freitas LGA, Jochaut D, Giraud AL, Van De Ville D. Neural responses in autism during movie watching : Inter-individual response variability co-varies with symptomatology. Neuroimage. 2020 : 116571.

Naturalistic movie paradigms are exquisitely dynamic by nature, yet dedicated analytical methods typically remain static. Here, we deployed a dynamic inter-subject functional correlation (ISFC) analysis to study movie-driven functional brain changes in a population of male young adults diagnosed with autism spectrum disorder (ASD). We took inspiration from the resting-state research field in generating a set of whole-brain ISFC states expressed by the analysed ASD and typically developing (TD) subjects along time. Change points of state expression often involved transitions between different scenes of the movie, resulting in the reorganisation of whole-brain ISFC patterns to recruit different functional networks. Both subject populations showed idiosyncratic state expression at dedicated time points, but only TD subjects were also characterised by episodes of homogeneous recruitment. The temporal fluctuations in both quantities, as well as in cross-population dissimilarity, were tied to contextual movie cues. The prominent idiosyncrasy seen in ASD subjects was linked to individual symptomatology by partial least squares analysis, as different temporal sequences of ISFC states were expressed by subjects suffering from social and verbal communication impairments, as opposed to nonverbal communication deficits and stereotypic behaviours. Furthermore, the temporal expression of several of these states was correlated with the movie context, the presence of faces on screen, or overall luminosity. Overall, our results support the use of dynamic analytical frameworks to fully exploit the information obtained by naturalistic stimulation paradigms. They also show that autism should be understood as a multi-faceted disorder, in which the functional brain alterations seen in a given subject will vary as a function of the extent and balance of expressed symptoms.

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2. Dizitzer Y, Meiri G, Flusser H, Michaelovski A, Dinstein I, Menashe I. Comorbidity and health services’ usage in children with autism spectrum disorder : a nested case-control study. Epidemiol Psychiatr Sci. 2020 ; 29 : e95.

AIMS : Children with autism spectrum disorder (ASD) tend to suffer from various medical comorbidities. We studied the comorbidity burden and health services’ utilisation of children with ASD to highlight potential aetiologies and to better understand the medical needs of these children. METHODS : In this nested case-control study, ASD cases and controls - matched by age, sex and ethnicity in a 1:5 ratio - were sampled from all children born between 2009 and 2016 at a tertiary medical centre. Data were obtained from the hospital’s electronic database. Comorbid diagnoses were classified according to pathophysiological aetiology and anatomical/systemic classification of disease. Standard univariate and multivariate statistics were used to demonstrate comorbidities and health services’ utilisation patterns that are significantly associated with ASD. RESULTS : ASD children had higher rates of comorbidities according to both pathophysiological and anatomical/systemic classifications (p < 0.001). The most marked significant differences were observed for : hearing impairments (OR = 4.728 ; 95% CI 2.207-10.127) and other auricular conditions (OR = 5.040 ; 95% CI 1.759-14.438) ; neurological (OR = 8.198 ; 95% CI 5.690-11.813) and ophthalmological (OR = 3.381 ; 95% CI 1.617-7.068) conditions ; and ADD/ADHD (OR = 3.246 ; 95% CI 1.811-5.818). A subgroup analysis revealed a more profound case-control difference in anaemia rates among girls than in boys (OR = 3.25 ; 95% CI 1.04-10.19 v. OR = 0.74 ; 95% CI 0.33-1.64 respectively) and an opposite trend (larger differences in males than in females in cardiovascular diseases (OR = 1.99 ; 95% CI 1.23-3.23 v. OR = 0.76 ; 95% CI 0.17-3.45, respectively)). In addition, larger case-control differences were seen among Bedouin children than in Jewish children in a number of medical comorbidities (Breslow-Day test for homogeneity of odds ratio p-value <0.05). Finally, we found that children with ASD tended to be referred to the emergency department and to be admitted to the hospital more frequently than children without ASD, even after adjusting for their comorbidity burden (aOR = 1.28 ; 95% CI 1.08-1.50 and aOR = 1.28 ; 95% CI 1.11-1.47 for >1 referrals and admissions per year, respectively). CONCLUSIONS : The findings of this study contribute to the overall understanding of comorbid conditions and health services’ utilisation for children with ASD. The higher prevalences of comorbidities and healthcare services’ utilisation for children with ASD highlight the additional medical burden associated with this condition.

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3. Egorova O, Myte R, Schneede J, Hagglof B, Bolte S, Domellof E, Ivars A’roch B, Elgh F, Ueland PM, Silfverdal SA. Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring : a study of 62 serum biomarkers. Mol Autism. 2020 ; 11 : 7.

Background : Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. Methods : Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. Results : We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase : 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. Conclusions : Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

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4. Emam B, Shahsavani A, Khodagholi F, Zarandi SM, Hopke PK, Hadei M, Behbahani H, Yarahmadi M. Effects of PM2.5 and gases exposure during prenatal and early-life on autism-like phenotypes in male rat offspring. Particle and fibre toxicology. 2020 ; 17(1) : 8.

BACKGROUND : Epidemiological studies have reported associations between elevated air pollution and autism spectrum disorders (ASD). However, we hypothesized that exposure to air pollution that mimics real world scenarios, is a potential contributor to ASD. The exact etiology and molecular mechanisms underlying ASD are not well understood. Thus, we assessed whether changes in OXTR levels may be part of the mechanism linking PM2.5/gaseous pollutant exposure and ASD. The current in-vivo study investigated the effect of exposure to fine particulate matter (PM2.5) and gaseous pollutants on ASD using behavioral and molecular experiments. Four exposure groups of Wistar rats were included in this study : 1) particulate matter and gaseous pollutants exposed (PGE), 2) gaseous pollutants only exposed (GE), 3) autism-like model (ALM) with VPA induction, and 4) clean air exposed (CAE) as the control. Pregnant dams and male pups were exposed to air pollutants from embryonic day (E0) to postnatal day (PND21). RESULTS : The average +/- SD concentrations of air pollutants were : PM2.5 : 43.8 +/- 21.1 mug/m(3), CO : 13.5 +/- 2.5 ppm, NO2 : 0.341 +/- 0.100 ppm, SO2 : 0.275 +/- 0.07 ppm, and O3 : 0.135 +/- 0.01 ppm. The OXTR protein level, catalase activity (CAT), and GSH concentrations in the ALM, PGE, and GE rats were lower than those in control group (CAE). However, the decrements in the GE rats were smaller than other groups. Also in behavioral assessments, the ALM, PGE, and GE rats demonstrated a repetitive /restricted behavior and poor social interaction, but the GE rats had weaker responses compared to other groups of rats. The PGE and GE rats showed similar trends in these tests compared to the VPA rats. CONCLUSIONS : This study suggested that exposure to ambient air pollution contributed to ASD and that OXTR protein may serve as part of the mechanism linking them.

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5. Filice F, Schwaller B, Michel TM, Grunblatt E. Profiling parvalbumin interneurons using iPSC : challenges and perspectives for Autism Spectrum Disorder (ASD). Mol Autism. 2020 ; 11(1) : 10.

Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology-and its numerous comorbid conditions-heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short : PVALB neurons) are critically implicated in the regulation of cortical networks’ activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention.New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during "neurodevelopment ex vivo."

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6. Hirokawa K, Kimura T, Ikehara S, Honjo K, Ueda K, Sato T, Iso H. Associations Between Broader Autism Phenotype and Dietary Intake : A Cross-Sectional Study (Japan Environment & Children’s Study). J Autism Dev Disord. 2020.

The purpose of the present study was to investigate associations of dietary intake including vitamin D, folate, and n-3 and n-6 polyunsaturated fatty acids (PUFA) in pregnant women with broad autism phenotype (BAP). The Japan Environment and Children’s Study is a government-funded birth cohort study. All complete data of 92,011 were analyzed. The Japanese version of the Autism Spectrum Quotient was used to assess mothers’ BAP level, and a food frequency questionnaire was used to estimate their dietary intake. Mothers with BAP consumed less vegetables, fruits, and fish and shellfish, and they consumed lower folate, vitamin C, vitamin D, and n-3 PUFA than their counterparts. Dietary intervention should be considered for pregnant women with high BAP scores.

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7. Laczmanska I, Stembalska A, Zlocinska M, Kozlowska J, Skiba P, Pesz K, Slezak R, Smigiel R, Jakubiak A, Misiak B, Sasiadek MM. Multiplex ligation-dependent probe amplification as a screening test in children with autism spectrum disorders. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2020.

BACKGROUND : Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders, characterized by the presence of various symptoms related to deficits in communication and social interactions as well as stereotyped and repetitive behavior. Increasing evidence indicates the contribution of genetic factors in the etiology of ASDs. Genetic diagnosis in ASDs is based on identifying chromosome aberrations, microaberrations and point mutations in specific genes. One of the diagnostic tools is multiplex ligase-dependent probe amplification (MLPA) with a set of probes dedicated to ASDs (SALSA MLPA P343 Autism-1 ; MRC-Holland BV, Amsterdam, the Netherlands) targeting the genes located in the regions 15q11-q13, 16p11 and the SHANK3 gene in the 22q13 region. OBJECTIVES : Our study included 240 patients referred to the clinical genetics unit because of ASDs and/or developmental delay and/or an intellectual disability. Before genetic testing, the patients underwent a comprehensive medical work-up. MATERIAL AND METHODS : Multiplex ligase-dependent probe amplification was performed in 256 DNA samples from 240 probands and 16 family members using the SALSA MLPA P343 Autism-1 probe mix (MRC-Holland BV) according to the manufacturer’s protocol. RESULTS : We obtained 234 normal results and 22 abnormal results (15 probands and 7 abnormal results for probands’ parents or siblings). We diagnosed 1 16p11 microdeletion syndrome and 1 16p11 microduplication syndrome. We also found 3 deletions and 1 duplication in 15q13 region including 2 or 3 genes and 9 single probe alterations in the regions examined (1 duplication and 7 deletions). CONCLUSIONS : Due to the low costs, MLPA test may be a good tool for the genetic screening of ASD patients.

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8. Laverty C, Oliver C, Moss J, Nelson L, Richards C. Persistence and predictors of self-injurious behaviour in autism : a ten-year prospective cohort study. Mol Autism. 2020 ; 11 : 8.

Background : Self-injurious behaviours, such as head banging, hair pulling, skin picking and scratching, are common in individuals with autism. Despite high prevalence rates, there is a paucity of longitudinal research to refine models of risk and mechanism and inform service planning. In this longitudinal study, we investigated self-injury in a cohort of individuals with autism over 10 years to identify behavioural and demographic characteristics associated with persistent self-injury. Methods : Carers of 67 individuals with autism completed questionnaires relating to the presence of self-injury and relevant risk markers at T 1 (mean [SD] age in years 13.4 [7.7]) and T 3 (mean [SD] age in years 23.9 [7.7]) 10 years later. Forty-six of these also took part at T 2 (3 years after initial participation). Analysis assessed demographic and behavioural risk markers for self-injury, as well as the predictive value of items assessed at T 1and T 2. Results : Self-injury was persistent in 44% of individuals over the 10-year period, with behavioural characteristics of impulsivity (p < .001) and overactivity (p = .002), identified as risk markers for persistence. A predictive model of self-injury was derived from LASSO analysis, with baseline impulsivity, interest and pleasure, stereotyped behaviour, social communication and adaptive functioning predicting self-injury over 10 years. Conclusions : In this unique longitudinal investigation into the persistence of self-injury in a non-clinical sample of individuals with autism over a 10 year period, we have identified a novel, robust and stable profile of behavioural characteristics associated with persistent self-injury. Findings support an early intervention strategy targeted towards individuals identified to be at a higher risk of developing self-injurious behaviour.

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9. Masri AT, Khatib F, Al Qudah A, Nafi O, Almomani M, Bashtawi M, Alomari F, Qutifan S, Qutifan A. Parental use of conventional and complementary therapy for autism in Jordan. Complement Ther Med. 2020 ; 48 : 102275.

OBJECTIVE : We investigated parental use of conventional therapies and complementary and alternative medicine (CAM) for children with autism in Jordan. METHOD : This prospective cross-sectional study was conducted from February 2018 through December 2018 at the paediatric neurology clinics of three tertiary referral hospitals in Jordan. The accompanying parent was interviewed to complete a structured questionnaire. RESULTS : 274 parents were interviewed. The most common medications used were those to treat hyperactivity (150 ; 54.7 %), anticonvulsants (60 ; 21.9 %), and sleep aids (6 ; 2.1 %). CAM was used by 129 parents (47.0 %). A casein-free diet was the most commonly used dietary modification (24 ; 8.7 %), while fish oil (Omega-3) was the most common supplement used (96 ; 35.0 %). Hyperbaric oxygen, chelation therapy, and antifungal treatment were also occasionally used. Higher parental education levels and access to rehabilitation services correlated with higher CAM use (p < 0.05).

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10. Matsuo K, Yabuki Y, Fukunaga K. 5-aminolevulinic acid inhibits oxidative stress and ameliorates autistic-like behaviors in prenatal valproic acid-exposed rats. Neuropharmacology. 2020 : 107975.

Autism spectrum disorders (ASDs) constitute a neurodevelopmental disorder characterized by social deficits, repetitive behaviors, and learning disability. Oxidative stress and mitochondrial dysfunction are associated with ASD brain pathology. Here, we used oxidative stress in prenatal valproic acid (VPA)-exposed rats as an ASD model. After maternal VPA exposure (600mg/kg, p.o.) on embryonic day (E) 12.5, temporal analyses of oxidative stress in the brain using an anti-4-hydroxy-2-nonenal antibody revealed that oxidative stress was increased in the hippocampus after birth. This was accompanied by aberrant enzymatic activity in the mitochondrial electron transport chain and reduced adenosine triphosphate (ATP) levels in the hippocampus. VPA-exposed rats exhibited impaired spatial reference and object recognition memory alongside impaired social behaviors and repetitive behaviors. ASD-like behaviors including learning and memory were rescued by chronic oral administration of 5-aminolevulinic acid (5-ALA ; 30mg/kg/day) and intranasal administration of oxytocin (OXT ; 12mug/kg/day), a neuropeptide that improves social behavior in ASD patients. 5-ALA but not OXT treatment ameliorated oxidative stress and mitochondrial dysfunction in the hippocampus of VPA-exposed rats. Fewer parvalbumin-positive interneurons were observed in VPA-exposed rats. Both 5-ALA and OXT treatments augmented the number of parvalbumin-positive interneurons. Collectively, our results indicate that oral 5-ALA administration ameliorated oxidative stress and mitochondrial dysfunction, suggesting that 5-ALA administration improves ASD-like neuropathology and behaviors via mechanisms different to those of OXT.

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11. Salaeva D, Tarasoff LA, Brown HK. Health care utilisation in infants and young children born to women with intellectual and developmental disabilities : A systematic review and meta-analysis. J Intellect Disabil Res. 2020.

BACKGROUND : Mothers with intellectual and developmental disabilities (IDD) experience socio-economic and health disparities which could impact their offspring’s health care utilisation. We systematically reviewed evidence on health care utilisation in infants and young children of women with and without IDD. METHODS : MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from inception to October 2019 for studies examining preventive care, immunisations, emergency department visits, and hospitalisations. Data extraction and quality assessment were performed using standardised tools. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models for outcomes with data available from >/=3 studies. RESULTS : Four articles describing three cohort studies and one cross-sectional study met our criteria. Maternal IDD status was associated with increased neonatal intensive care unit admission rates (pooled OR 2.03 ; 95% CI 1.31, 3.13). There were no differences in immunisation rates or hospitalisations. CONCLUSIONS : Few studies have examined the impact of maternal IDD status on health care utilisation in their infants and young children. More high-quality studies are needed.

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12. Samadi SA. Parental Beliefs and Feelings about Autism Spectrum Disorder in Iran. Int J Environ Res Public Health. 2020 ; 17(3).

BACKGROUND : This study provides information on beliefs that parents of children with autism hold in Iran. The main focus is on their beliefs about the cause and the way that this condition is explained based on the first signs that made them be concerned for their children. METHOD : To attain the aims of this study, 43 parents of children with ASD (27 mothers and 16 fathers) were recruited and interviewed in two sessions in their home. A mixed method approach was used to understand Iranian parents’ reaction to receive diagnosis for their children. RESULTS : Based on findings for the identification, description, and treatment of ASD in Iran, it is argued that since Iranian parents had their special justification regarding their experience with ASD, early child development and interventions must be understood within cultural context. Culturally informed research on ASD is vital to boost awareness of the importance of understanding parental concerns and their need for educational and psychological services in countries in which autism is less known, undiagnosed, misdiagnosed, or even stigmatized. Understanding the difference in ASD meaning across cultures urges stakeholders such as service providers and policymakers to accept and appreciate cultural and individual diversities in the present century.

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13. Sihombing NRB, Cai S, Wong DPW, Guan M, Chong SS, Faradz SMH, Winarni TI. Repeat expansion and methylation-sensitive triplet-primed polymerase chain reaction for fragile X mental retardation 1 gene screening in institutionalised intellectually disabled individuals. Singapore medical journal. 2020.

INTRODUCTION : Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID. METHODS : A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax Identification, Sizing and Methylation Status Kits. RESULTS : Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%. CONCLUSION : Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.

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14. Southwell DG, Seifikar H, Malik R, Lavi K, Vogt D, Rubenstein JL, Sohal VS. Interneuron transplantation rescues social behavior deficits without restoring wild-type physiology in a mouse model of autism with excessive synaptic inhibition. J Neurosci. 2020.

Manipulations that enhance GABAergic inhibition have been associated with improved behavioral phenotypes in autism models, suggesting that autism may be treated by correcting underlying deficits of inhibition. Interneuron transplantation is a method for increasing recipient synaptic inhibition, and it has been considered a prospective therapy for conditions marked by deficient inhibition, including neuropsychiatric disorders. It is unknown, however, whether interneuron transplantation may be therapeutically effective only for conditions marked by reduced inhibition, and it is also unclear whether transplantation improves behavioral phenotypes solely by normalizing underlying circuit defects. To address these questions, we studied the effects of interneuron transplantation in male and female mice lacking the autism-associated gene, Pten, in GABAergic interneurons. Pten mutant mice exhibit social behavior deficits, elevated synaptic inhibition in prefrontal cortex, abnormal baseline and social interaction-evoked electrocencephalogram (EEG) signals, and an altered composition of cortical interneuron subtypes. Transplantation of wild type embryonic interneurons from the medial ganglionic eminence into the prefrontal cortex of neonatal Pten mutants rescued social behavior despite exacerbating excessive levels of synaptic inhibition. Furthermore, transplantation did not normalize recipient EEG signals measured during baseline states. Interneuron transplantation can thus correct behavioral deficits even when those deficits are associated with elevated synaptic inhibition. Moreover, transplantation does not exert therapeutic effects solely by restoring wild type circuit states. Our findings indicate that interneuron transplantation could offer a novel cell-based approach to autism treatment, while challenging assumptions that effective therapies must reverse underlying circuit defects.Significance StatementImbalances between neural excitation and inhibition are hypothesized to contribute to the pathophysiology of autism. Interneuron transplantation is a method for altering recipient inhibition, and it has been considered a prospective therapy for neuropsychiatric disorders, including autism. Here the authors have examined the behavioral and physiological effects of interneuron transplantation in a mouse genetic model of autism. They demonstrate that transplantation rescues recipient social interaction deficits without correcting a common measure of recipient inhibition, or circuit-level physiological measures. These findings demonstrate interneuron transplantation can exert therapeutic behavioral effects without necessarily restoring wild type circuit states, while highlighting the potential of interneuron transplantation as an autism therapy.

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15. Vovou F, Hull L, Petrides KV. Mental health literacy of ADHD, autism, schizophrenia, and bipolar disorder : a cross-cultural investigation. Journal of mental health (Abingdon, England). 2020 : 1-11.

Background : Mental health literacy (MHL) is linked to help-seeking behaviours. Although lay people are not always well aware of mental health conditions, few international campaigns and interventions have been developed to raise awareness across cultures.Aims : To investigate MHL cross-culturally and to identify factors that are associated with MHL.Method : Using an online survey, 506 participants (103 Greek, 108 UK, 146 USA, 149 other nationality) read and labelled five vignettes of individuals with Autism, ADHD, Schizophrenia, Bipolar disorder and a healthy control. Factors influencing response, confidence and accuracy were compared across all participants, and the effect of various demographics on accurate labelling was compared between countries.Results : Recognition rates were higher than in previous investigations : 75.5% of participants recognised the Healthy vignette, 71.1% ADHD, 61.7% Autism, 56.6% Schizophrenia and 31.6% Bipolar. MHL varied across different countries, with religion, language spoken, and education having the greatest effects. Personal experience of mental illness partially affected MHL.Conclusions : MHL is relatively high for some mental health conditions, but public knowledge of other conditions is still poor. Factors influencing MHL vary across countries.

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