1. Abib RT, Gaman A, Dargel AA, Tamouza R, Kapczinski F, Gottfried C, Leboyer M. {{Intracellular Pathogen Infections and Immune Response in Autism}}. {Neuroimmunomodulation}. 2018: 1-9.
BACKGROUND/AIMS: Perinatal exposure to infections during critical developmental periods is a promising area of study in autism spectrum disorder (ASD). Epidemiological data has highlighted this relationship, pointing out significant correlations between perinatal exposure to pathogens and the occurrence of ASD. The aim of this review is to critically examine the present state of the art on intracellular pathogenic infection during pregnancy and postnatally, pointing out possible correlations with the development of ASD. METHODS: We reviewed and collected studies concerning potential associations between intracellular pathogens like viral, bacterial, and parasite infection and the risk of ASD. RESULTS: We included 14 publications, considering bacterial and/or viral infection that demonstrated the potential to trigger ASD. Nine case-control studies were included and 5 of them reported an association between infections and ASD. One of the 2 cohorts investigated demonstrated that maternal infection increased the risk of ASD in the offspring. Three cross-sectional studies demonstrated that ASD patients presented with chronic infections and active neuroinflammatory processes. Most of the reports suggest inflammatory response as a common factor, and interleukin 6 appears to be a key-player in this process. CONCLUSION: The immune responses generated by organisms that cause perinatal maternal infection, i.e., bacteria, viruses, or parasites, have been associated with the development of autism in offspring. Physiological changes transmitted from the mother during chronic or acute inflammation should be further investigated so that modulatory preventive measures can be developed.
2. Andreae LC, Basson MA. {{Sex bias in autism: new insights from Chd8 mutant mice?}}. {Nat Neurosci}. 2018.
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3. Bury SM, Hedley D, Uljarevic M, Dissanayake C, Gal E. {{If you’ve employed one person with autism …: An individual difference approach to the autism advantage at work}}. {Autism}. 2018: 1362361318794937.
In this letter to the editor, we comment on the ‘autism advantage’ – the idea that superior skills associated with autism (e.g. attention to detail) present a talent in employment – an example of which is a recent discussion by Austin and Pisano. We welcome advocacy that raises awareness around the strengths and capabilities of people with autism, and also the need to reform human resource management processes that disadvantage them. However, we are concerned that, by highlighting certain stereotypes (e.g. the ‘talented nerd lacking social graces’), the heterogeneity of autism may be overlooked and support needs downplayed. Furthermore, not appreciating individual differences might result in a misalignment between work-profile and employment, pressure to outperform peers without autism and a failure to appreciate the diverse interests of people with autism. We argue that an individual differences approach will prove more sustainable for improving long-term employment outcomes.
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4. Duret P, Samson F, Pinsard B, Barbeau EB, Bore A, Soulieres I, Mottron L. {{Gyrification changes are related to cognitive strengths in autism}}. {Neuroimage Clin}. 2018; 20: 415-23.
Background: Behavioral, cognitive and functional particularities in autism differ according to autism subgroups and might be associated with domain-specific cognitive strengths. It is unknown whether structural changes support this specialization. We investigated the link between cortical folding, its maturation and cognitive strengths in autism subgroups presenting verbal or visuo-spatial peaks of abilities. Methods: We measured gyrification, a structural index related to function, in 55 autistic participants with (AS-SOD, N=27) or without (AS-NoSOD, N=28) a speech onset delay (SOD) with similar symptom severity but respectively perceptual and verbal cognitive strengths, and 37 typical adolescents and young adults matched for intelligence and age. We calculated the local Gyrification Index (lGI) throughout an occipito-temporal region of interest and independently modeled age and peak of ability effects for each group. Results: Unique gyrification features in both autistic groups were detected in localized clusters. When comparing the three groups, gyrification was found lower in AS-SOD in a fusiform visual area, whereas it was higher in AS-NoSOD in a temporal language-related region. These particular areas presented age-related gyrification differences reflecting contrasting local maturation pathways in AS. As expected, peaks of ability were found in a verbal subtest for the AS-NoSOD group and in the Block Design IQ subtest for the AS-SOD group. Conclusions: Irrespective of their direction, regional gyrification differences in visual and language processing areas respectively reflect AS-SOD perceptual and AS-NoSOD language-oriented peaks. Unique regional maturation trajectories in the autistic brain may underline specific cognitive strengths, which are key variables for understanding heterogeneity in autism.
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5. Guo Q, Yin X, Qiao M, Jia Y, Chen D, Shao J, Lebaron TW, Gao Y, Shi H, Jia B. {{Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring}}. {Frontiers in behavioral neuroscience}. 2018; 12: 170.
Due to its anti-inflammatory and anti-oxidative effects, recent research has demonstrated that molecular hydrogen can serve as a new medical approach for depression, anxiety and traumatic brain injury. However, its potential effects on neurodevelopmental diseases, such as autism are still elusive. The present study aims to investigate the potential effects of hydrogen-rich water (HRW) administration on valproic acid (VPA)-induced autistic-like behavioral deficits, and the associated underlying mechanism in adolescent mice offspring. Pregnant ICR mice were randomly divided into five groups (n = 6). One group was injected with saline (NAV group) and provided hydrogen-free water. The other four groups were injected with VPA (600 mg/kg, intraperitoneally, i.p.) on pregnant day (PND) 12.5. One group was provided with hydrogen-free water (VEH group) and the other three groups were provided HRW at different segments, postnatal day 1 (PND 1) to PND 21 (PHV group), PND 13 to PND 21 (PVS group) or from PND 13 to postnatal day 42 (PVL group). Behavioral tests, including open field, novelty suppressed feeding (NSF), hot plate, social interaction (SI) and contextual fear memory tests were conducted between postnatal day 35-42. We found that HRW administration significantly reversed the autistic-like behaviors induced by maternal VPA exposure in the adolescent offspring of both male and female adolescent offspring. Furthermore, HRW administration significantly reversed the alternation of serum levels of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), but without any effects on the BDNF levels in maternal VPA-exposed mice offspring. These data suggest the need for additional research on HRW as a potential preventive strategy for autism and related disorders. Lay Summary: Maternal VPA injection induces autistic-like behavioral deficits in adolescent mice offspring. HRW administration ameliorates autistic-like behavioral deficits. HRW administration reverses the alternation of serum levels of IL-6 and TNF-alpha induced by VPA.
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6. Jia H, Li Y, Yu D. {{Attenuation of long-range temporal correlations of neuronal oscillations in young children with autism spectrum disorder}}. {Neuroimage Clin}. 2018; 20: 424-32.
Although autism spectrum disorder (ASD) was previously found to be associated with aberrant brain structure, neuronal amplitudes and spatial neuronal interactions, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. Here, the hemoglobin concentration signals (i.e., oxy-Hb and deoxy-Hb) of young children with ASD and typically developing (TD) children were recorded via functional near infrared spectroscopy (fNIRS) when they were watching a cartoon. The long-range temporal correlations (LRTCs) of hemoglobin concentration signals were quantified using detrended fluctuation analysis (DFA). Compared with TD group, the DFA exponents of young children with ASD were significantly smaller over left temporal region for oxy-Hb signal, and over bilateral temporo-occipital regions for deoxy-Hb signals, indicating a shift-to-randomness of brain oscillations in the children with ASD. Testing the relationship between age and DFA exponents revealed that this association could be modulated by autism. The correlation coefficients between age and DFA exponents were significantly more positive in TD group, compared to those in ASD group over several brain regions. Furthermore, the DFA exponents of oxy-Hb in left temporal region were negatively correlated with autistic symptom severity. These results suggest that the decreased DFA exponent of hemoglobin concentration signals may be one of the pathologic changes in ASD, and studying the temporal structure of brain activity via fNIRS technique may provide physiological indicators for autism.
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7. Jung CR, Lin YT, Hwang BF. {{Correction: Air Pollution and Newly Diagnostic Autism Spectrum Disorders: A Population-Based Cohort Study in Taiwan}}. {PLoS One}. 2018; 13(8): e0202996.
[This corrects the article DOI: 10.1371/journal.pone.0075510.].
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8. Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P. {{Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol}. 2018.
OBJECTIVE: A recent double-blind randomized placebo-controlled study demonstrated 3-month efficacy and safety of a novel pediatric-appropriate prolonged-release melatonin (PedPRM) for insomnia in children and adolescents with autism spectrum disorder (ASD) and neurogenetic disorders (NGD) with/without attention-deficit/hyperactivity disorder comorbidity. Long-term efficacy and safety of PedPRM treatment was studied. METHODS: A prospective, open-label efficacy and safety follow-up of nightly 2, 5, or 10 mg PedPRM in subjects who completed the 13-week double-blind trial (51 PedPRM; 44 placebo). Measures included caregiver-reported Sleep and Nap Diary, Composite Sleep Disturbance Index (CSDI), caregiver’s Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and quality of life (WHO-5 Well-Being Index). RESULTS: Ninety-five subjects (74.7% males; mean [standard deviation] age, 9 [4.24]; range, 2-17.5 years) received PedPRM (2/5 mg) according to the double-blind phase dose, for 39 weeks with optional dose adjustment (2, 5, or 10 mg/day) after the first 13 weeks. After 52 weeks of continuous treatment (PedPRM-randomized group) subjects slept (mean [SE]) 62.08 (21.5) minutes longer (p = 0.007); fell asleep 48.6 (10.2) minutes faster (p < 0.001); had 89.1 (25.5) minutes longer uninterrupted sleep episodes (p = 0.001); 0.41 (0.12) less nightly awakenings (>50% decrease; p = 0.001); and better sleep quality (p < 0.001) compared with baseline. The placebo-randomized group also improved with PedPRM. Altogether, by the end of 39-week follow-up, regardless of randomization assignment, 55/72 (76%) of completers achieved overall improvement of >/=1 hour in total sleep time (TST), sleep latency or both, over baseline, with no evidence of decreased efficacy. In parallel, CSDI child sleep disturbance and caregivers’ satisfaction of their child’s sleep patterns (p < 0.001 for both), PSQI global (p < 0.001), and WHO-5 (p = 0.001) improved in statistically significant and clinically relevant manner (n = 72) compared with baseline. PedPRM was generally safe; most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2% of patients). CONCLUSION: PedPRM, an easily swallowed formulation shown to be efficacious versus placebo, is an efficacious and safe option for long-term treatment (up to 52 weeks reported here) of children with ASD and NGD who suffer from insomnia and subsequently improves caregivers' quality of life. Lien vers le texte intégral (Open Access ou abonnement)
9. Park BY, Misra DP, Moye J, Miller RK, Croen L, Fallin MD, Walker C, Newschaffer CJ, Salafia CM. {{Placental gross shape differences in a high autism risk cohort and the general population}}. {PLoS One}. 2018; 13(8): e0191276.
A growing body of evidence suggests that prenatal environment is important in Autism Spectrum Disorder (ASD) etiology. In this study, we compare placental shape features in younger siblings of children with ASD, who themselves are at high ASD risk, to a sample of low risk peers. Digital photographs of the fetal placenta surface and of the sliced placental disk from 129 high ASD risk newborns and from 267 newborns in the National Children’s Study Vanguard pilot were analysed to extract comparable measures of placental chorionic surface shape, umbilical cord displacement and disk thickness. Placental thickness measures were moderately higher in siblings of ASD cases. The placentas of ASD-case siblings were also rounder and more regular in perimeter than general population placentas. After stratification by sex, these across-group differences persisted for both sexes but were more pronounced in females. No significant differences were observed in cord insertion measures. Variations in placental shape features are generally considered to reflect flexibility in placental growth in response to changes in intrauterine environment as the placenta establishes and matures. Reduced placental shape variability observed in high ASD risk siblings compared to low-risk controls may indicate restricted ability to compensate for intrauterine changes.
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10. Stacey TL, Froude EH, Trollor J, Foley KR. {{Leisure participation and satisfaction in autistic adults and neurotypical adults}}. {Autism}. 2018: 1362361318791275.
Leisure participation is important for well-being and has been attributed to improved quality of life for autistic individuals. Rigorous studies exploring the leisure participation of autistic adults are sparse. This study aimed to compare the type of leisure activity and frequency of participation between autistic adults and neurotypical adults as well as compare and identify factors associated with their leisure satisfaction. Data for 145 autistic and 104 neurotypical adults were obtained from time point one of the Australian Longitudinal Study of Adults with Autism. The primary outcome measure used was the Leisure Satisfaction Scale. Autistic adults were less satisfied with their leisure overall (mean = 3.29, standard deviation = 0.75) compared with neurotypical adults (mean = 3.69, standard deviation = 0.55). Multiple linear regression revealed being younger and reporting less depressive symptoms were significantly associated with higher leisure satisfaction in autistic but not neurotypical adults. Engagement in solitary leisure activities was comparable across participants, but socialising in person was predominated by neurotypical adults. Leisure activity preferences of autistic adults’ and the frequency of their leisure participation are important factors for clinicians to understand when working with this population and tailoring well-being interventions.
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11. Takahashi H, Nakamura T, Kim J, Kikuchi H, Nakahachi T, Ishitobi M, Ebishima K, Yoshiuchi K, Ando T, Stickley A, Yamamoto Y, Kamio Y. {{Acoustic Hyper-Reactivity and Negatively Skewed Locomotor Activity in Children With Autism Spectrum Disorders: An Exploratory Study}}. {Frontiers in psychiatry}. 2018; 9: 355.
Investigation of objective and quantitative behavioral phenotypes along with neurobiological endophenotypes might lead to increased knowledge of the mechanisms that underlie autism spectrum disorders (ASD). Here, we investigated the association between locomotor dynamics and characteristics of the acoustic startle response (ASR) and its modulation in ASD (n = 14) and typically developing (TD, n = 13) children. The ASR was recorded in response to acoustic stimuli in increments of 10 dB (65-105 dB SPL). We calculated the average ASR magnitude for each stimulus intensity and peak-ASR latency. Locomotor activity was continuously measured with a watch-type actigraph. We examined statistics of locomotor activity, such as mean activity levels and the skewness of activity. Children with ASD had a significantly greater ASR magnitude in response to a weak acoustic stimulus, which reflects acoustic hyper-reactivity. The skewness of all-day activity was significantly more negative in children with ASD than those with TD. Skewness of daytime activity was also more negative, although only of borderline statistical significance. For all children, the higher mean and more negatively skewed daytime activity, reflecting hyperactivity that was associated with sporadic large daytime « troughs, » was significantly correlated with acoustic hyper-reactivity. The more negatively skewed locomotor activity occurring in the daytime was also associated with impaired sensorimotor gating, examined as prepulse inhibition at a prepulse intensity of 70 dB. This comprehensive investigation of locomotor dynamics and the ASR extends our understanding of the neurophysiology that underlies ASD.
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12. Wiggins LD, Rubenstein E, Daniels J, DiGuiseppi C, Yeargin-Allsopp M, Schieve LA, Tian LH, Sabourin K, Moody E, Pinto-Martin J, Reyes N, Levy SE. {{A Phenotype of Childhood Autism Is Associated with Preexisting Maternal Anxiety and Depression}}. {Journal of abnormal child psychology}. 2018.
This study explored whether ASD phenotypes in the child were associated with a history of anxiety or depression in the mother. We hypothesized that an ASD profile in children characterized by mild delays and increased rates of dysregulation would be associated with preexisting maternal anxiety or depression. Participants were 672 preschool children with ASD and their mothers. Children were classified as ASD after a comprehensive developmental evaluation. Mothers reported whether a healthcare provider ever diagnosed them with anxiety or depression before the birth of their child. Four child ASD phenotypes were derived from latent class analysis: Mild Language Delay with Cognitive Rigidity (Type 1), Significant Developmental Delay with Repetitive Motor Behaviors (Type 2), General Developmental Delay (Type 3), and Mild Language and Motor Delay with Dysregulation (i.e., aggression, anxiety, depression, emotional reactivity, inattention, somatic complaints, and sleep problems) (Type 4). Type 2 ASD served as the referent category in statistical analyses. Results showed that 22.6% of mothers reported a diagnosis of anxiety or depression before the birth of their child. Maternal anxiety or depression was associated with 2.7 times the odds (95% confidence interval: 1.4, 5.3) of Type 4 or Dysregulated ASD in the child; maternal anxiety and depression was associated with 4.4 times the odds (95% confidence interval: 1.4, 14.0) of Type 4 or Dysregulated ASD in the child. Our findings suggest an association between Dysregulated ASD in the child and anxiety and depression in the mother. These findings can enhance screening methods and inform future research efforts.
