Pubmed du 19/04/17
1. Al-Mamari W, Idris AB, Al-Jabri M, Abdelsattar A, Al-Hinai F, Al-Hatmi M, Al-Raidan A. A Turning Point for Paediatric Developmental Services in Oman : Establishment of a national autism screening programme. Sultan Qaboos Univ Med J ;2017 (Feb) ;17(1):e125-e126.
2. Al-Mendalawi MD. Re : Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous Sclerosis Complex : Case reports and review of literature. Sultan Qaboos Univ Med J ;2017 (Feb) ;17(1):e127.
3. Alnemary FM, Alamri AS, Alamri YA. Characteristics of Arabic Websites with information on autism. Neurosciences (Riyadh) ;2017 (Apr) ;22(2):143-145.
OBJECTIVE : To explore the characteristics of Arabic websites with information on autism spectrum disorder (ASD). METHODS : The word autism in Arabic was entered into 2 popular search engines in September 2013 to locate the top 80 websites featuring the term. Websites were sorted using 10 characteristics, previously used to evaluate the characteristics of English websites with information on ASD. RESULTS : Most websites were registered using a .com top-level domain (69%), were an individual`s site, forum, or blog (44%), and were updated after September 2012 (60%) ; they contained images or texts that seemed to persuade viewers to purchase products (43%) ; they provided information with the name of author(s) (64%) ; they described the basic characteristics of ASD ; and they promoted various types of treatments, most of which lack empirical support (63%). However, few websites contained information with references to peer review resources (3%) or a warning statement that such information should not replace the opinion of a qualified professional (8%). CONCLUSION : Internet users may not find Arabic websites to be reliable sources to obtain information on ASD. Given the increased use of the internet, creation of websites that contain trusted information on ASD could potentially aid parents in accessing available services, help them learn about empirically validated interventions, and enable them to advocate for their children`s rights.
4. Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children. JAMA ;2017 (Apr 18) ;317(15):1544-1552.
Importance : Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded. Objective : To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder. Design, Setting, and Participants : Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014. Exposures : Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery. Main Outcomes and Measures : Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings. Results : There were 35906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years ; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86] ; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively ; adjusted HR, 1.60 [95% CI, 0.69-3.74]). Conclusions and Relevance : In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.
5. Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S. Fragile X syndrome : a review of clinical and molecular diagnoses. Ital J Pediatr ;2017 (Apr 19) ;43(1):39.
BACKGROUND : Fragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band : more than 99% of individuals have a CGG expansion (>200 triplets) in the 5’ UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures. DISCUSSION : FXS is a well-known condition ; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms. CONCLUSIONS : The clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden.
6. Costa LG, Chang YC, Cole TB. Developmental Neurotoxicity of Traffic-Related Air Pollution : Focus on Autism. Curr Environ Health Rep ;2017 (Apr 17)
PURPOSE OF REVIEW : Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. RECENT FINDINGS : Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions are certainly warranted.
7. Fluegge K. Cost-effectiveness of Wait Time Reduction in Behavioral Interventions for Autism. JAMA Pediatr ;2017 (Apr 17)
8. Hu Y, Ehli EA, Boomsma DI. MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum disorder : Current progress in genetic association studies, expression profiling, and translational research. Autism Res ;2017 (Apr 17)
MicroRNAs (miRNAs) are a group of small noncoding RNA molecules, 18-25 nucleotides in length, which can negatively regulate gene expression at the post-transcriptional level by binding to messenger RNAs. About half of all identified miRNAs in humans are expressed in the brain and display regulatory functions important for many biological processes related to the development of the central nervous system (CNS). Disruptions in miRNA biogenesis and miRNA-target interaction have been related to CNS diseases, including psychiatric disorders. In this review, we focus on the role of miRNAs in autism spectrum disorder (ASD) and summarize recent findings about ASD-associated genetic variants in miRNA genes, in miRNA biogenesis genes, and miRNA targets. We discuss deregulation of miRNA expression in ASD and functional validation of ASD-related miRNAs in animal models. Including miRNAs in studies of ASD will contribute to our understanding of its etiology and pathogenesis and facilitate the discrimination between different disease subgroups. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
9. Jansen A, Dieleman GC, Smit AB, Verhage M, Verhulst FC, Polderman TJC, Posthuma D. Gene-set analysis shows association between FMRP targets and autism spectrum disorder. Eur J Hum Genet ;2017 (Apr 19)
Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding biological mechanisms are largely unknown. Our objective is to investigate the contribution of common genetic variation to biological pathways functionally involved in ASD. We conducted gene-set analyses to identify ASD-associated functional biological pathways using the statistical tools MAGMA and INRICH. Gene-set selection was based on previously reported associations with psychiatric disorders and resulted in testing of specific synaptic and glial sets, a glutamate pathway gene-set, mitochondrial gene-sets and gene-sets consisting of fragile X mental retardation protein (FMRP) targets. In total 32 gene-sets were tested. We used Psychiatric Genomics Consortium genome-wide association studies summary statistics of ASD. The study is based on the largest ASD sample to date (N=5305). We found one significantly associated gene-set consisting of FMRP-targeting transcripts (MAGMA : p corr.=0.014, INRICH : p corr.=0.031 ; all competitive P-values). The results indicate the involvement of FMRP-targeted transcripts in ASD in common genetic variation. This novel finding is in line with the literature as FMRP has been linked to fragile X syndrome, ASD and cognitive development in whole-exome sequencing and copy number variant studies. This gene-set has also been linked to Schizophrenia suggesting that FMRP-targeted transcripts might be involved in a general mechanism with shared genetic etiology between psychiatric disorders.European Journal of Human Genetics advance online publication, 19 April 2017 ; doi:10.1038/ejhg.2017.55.
10. Kanat M, Spenthof I, Riedel A, van Elst LT, Heinrichs M, Domes G. Restoring effects of oxytocin on the attentional preference for faces in autism. Transl Psychiatry ;2017 (Apr 18) ;7(4):e1097.
Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin’s effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin’s anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.
11. King BH. Association Between Maternal Use of SSRI Medications and Autism in Their Children. JAMA ;2017 (Apr 18) ;317(15):1568-1569.
12. Lammert DB, Middleton FA, Pan J, Olson EC, Howell BW. The de novo Autism Spectrum Disorder RELN R2290C Mutation Reduces Reelin Secretion and Increases Protein Disulfide Isomerase Expression. J Neurochem ;2017 (Apr 17)
Despite the recent identification of over 40 missense heterozygous RELN mutations in ASD, none of these has been functionally characterized. Reelin is an integral signaling ligand for proper brain development and postnatal synapse function - properties likely disrupted in ASD patients. We find that the R2290C mutation, which arose de novo in an affected ASD proband, and other analogous mutations in RXR domains reduce protein secretion. Closer analysis of RELN R2290C heterozygous neurospheres reveals upregulation of Protein Disulfide Isomerase A1, best known as an ER-chaperone protein, which has been linked to neuronal pathology. This effect is recapitulated in a heterozygous RELN mouse mutant that is characterized by defective Reelin secretion. These findings suggest that both a deficiency in Reelin signaling and pathologic impairment of Reelin secretion may contribute to ASD risk. This article is protected by copyright. All rights reserved.
13. Lee NA, Furrow JL, Bradley BA. Emotionally Focused Couple Therapy for Parents Raising a Child with an Autism Spectrum Disorder : A Pilot Study. J Marital Fam Ther ;2017 (Apr 17)
Many couples raising children diagnosed with an Autism Spectrum Disorder (ASD) are often resilient in confronting unique parental demands, while others experience greater risk for relational distress. Research has shown that Emotionally Focused Couple Therapy (EFT) is efficacious with couples raising chronically ill children and relevant to the relational demands of parents of children diagnosed with an ASD. This pilot study tested the effectiveness of EFT with seven couples presenting with moderate to severe distress, who were also parents of a child diagnosed with an ASD. Results demonstrated significant decreases in marital distress at posttreatment and 6-month follow-up. The study also identified several unique themes associated with couple distress and the parenting experiences of this population.
14. Mackus M, Kruijff D, Otten LS, Kraneveld AD, Garssen J, Verster JC. Differential Gender Effects in the Relationship between Perceived Immune Functioning and Autistic Traits. Int J Environ Res Public Health ;2017 (Apr 12) ;14(4)
Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD). The current study explores the relationship between perceived immune functioning and experiencing ASD traits in healthy young adults. N = 410 students from Utrecht University completed a survey on immune functioning and autistic traits. In addition to a 1-item perceived immune functioning rating, the Immune Function Questionnaire (IFQ) was completed to assess perceived immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was completed to examine variation in autistic traits, including the domains "social insights and behavior", "difficulties with change", "communication", "phantasy and imagination", and "detail orientation". The 1-item perceived immune functioning score did not significantly correlate with the total AQ score. However, a significant negative correlation was found between perceived immune functioning and the AQ subscale "difficulties with change" (r = -0.119, p = 0.019). In women, 1-item perceived immune functioning correlated significantly with the AQ subscales "difficulties with change" (r = -0.149, p = 0.029) and "communication" (r = -0.145, p = 0.032). In men, none of the AQ subscales significantly correlated with 1-item perceived immune functioning. In conclusion, a modest relationship between perceived immune functioning and several autistic traits was found.
15. Mezzacappa A, Lasica PA, Gianfagna F, Cazas O, Hardy P, Falissard B, Sutter-Dallay AL, Gressier F. Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure : A Systematic Review and Meta-analysis. JAMA Pediatr ;2017 (Apr 17)
Importance : Several studies have examined the links between prenatal exposure to antidepressants and autism spectrum disorders (ASDs) in children, with inconsistent results, especially regarding the impact of the trimester of exposure. Objective : To perform a systematic review of the literature and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception. Data Sources : PubMed, EMBASE, and PsycINFO databases up to May 2016 were searched in June 2016 for observational studies. For the meta-analyses, data were analyzed on RevMan version 5.2 using a random-effect model. For the review, studies were included if they had been published and were cohort or case-control studies, and for the meta-analysis, studies were included if they were published studies and the data were not derived from the same cohorts. Study Selection : We included all the studies that examined the association between ASDs and antenatal exposure to antidepressants. Data Extraction and Synthesis : Three reviewers independently screened titles and abstracts, read full-text articles, and extracted data. The quality of the studies was also assessed. Main Outcomes and Measures : Primary outcome was the association between antidepressants during pregnancy and ASDs. Secondary outcomes were the associations between antidepressants in each individual trimester or before pregnancy and ASDs. Results : Our literature search identified 10 relevant studies with inconsistent results. For prenatal exposure, the meta-analysis on the 6 case-control studies (117737 patients) evidenced a positive association between antidepressant exposure and ASDs (odds ratio [OR], 1.81 ; 95% CI, 1.49-2.20). The association was weaker when controlled for past maternal mental illness (OR, 1.52 ; 95% CI, 1.09-2.12). A similar pattern was found whatever the trimester of exposure considered (first trimester : OR, 2.09, 95% CI,1.66-2.64 ; second : OR, 2.00, 95% CI, 1.55-2.59 ; and third : OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental illness : first trimester : OR, 1.79 ; 95% CI, 1.27-2.52, second : OR, 1.67, 95% CI, 1.14-2.45 ; and third : OR, 1.54, 95% CI, 0.82-2.90). No association was found when the 2 cohort studies were pooled (772331 patients) for the whole pregnancy (hazard ratio, 1.26 ; 95% CI, 0.91-1.74) or for the first trimester. In addition, preconception exposure to antidepressants was significantly associated with an increased risk for ASDs (OR controlled for past maternal illness, 1.77 ; 95% CI, 1.49-2.09). Conclusions and Relevance : There is a significant association between increased ASD risk and maternal use of antidepressants during pregnancy ; however, it appears to be more consistent during the preconception period than during each trimester. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for ASDs. Future studies should address the problem of this potential confounder.
16. Oberlander TF, Zwaigenbaum L. Disentangling Maternal Depression and Antidepressant Use During Pregnancy as Risks for Autism in Children. JAMA ;2017 (Apr 18) ;317(15):1533-1534.
17. Parker W, Hornik CD, Bilbo S, Holzknecht ZE, Gentry L, Rao R, Lin SS, Herbert MR, Nevison CD. The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism. J Int Med Res ;2017 (Apr) ;45(2):407-438.
The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.
18. Patowary A, Nesbitt R, Archer M, Bernier R, Brkanac Z. Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder. Autism Res ;2017 (Apr 17)
Autism is a complex genetic disorder where both de-novo and inherited genetics factors play a role. Next generation sequencing approaches have been extensively used to identify rare variants associated with autism. To date, all such studies were focused on nuclear genome ; thereby leaving the role of mitochondrial DNA (mtDNA) variation in autism unexplored. Recently, analytical tools have been developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA sequence derived from whole-exome sequencing in 10 multiplex families. In one of the families we have identified two variants of interest in MT-ND5 gene that were previously determined to impair mitochondrial function. In addition in a second family we have identified two VOIs ; mtDNA variant in MT-ATP6 and nuclear DNA variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain Complex. Our findings provide further support for the role of mitochondria in ASD and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets a stage for further comprehensive genetic investigations of the role of mitochondria in autism. Autism Res 2017. (c) 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
19. Penner M. Cost Effectiveness of Wait Time Reduction in Behavioral Interventions for Autism-Reply. JAMA Pediatr ;2017 (Apr 17)
20. Su X, Yuan W, Chen J, Miao M, Olsen J, Pedersen LH, Liang H, Li J. Prenatal exposure to beta2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring. Pharmacoepidemiol Drug Saf ;2017 (Apr 19)
PURPOSE : We aimed to examine the risk of autism spectrum disorders (ASDs) in the offspring who were exposed to maternal use of beta2-adrenoreceptor agonist (beta2AA) during pregnancy. METHODS : This is a population-based cohort study including all live singleton births in Denmark from 1 January 1997 to 31 December 2008. Children born to mothers who used beta2AA during pregnancy were categorized as exposed, and all other children were included in the unexposed group. Cases of ASDs were identified from the Danish Psychiatric Central Register and the Danish Patient Register. Incidence rate ratio (IRR) and 95% confidence interval were estimated by Poisson regression models. RESULTS : Among 751 888 children in the cohort, 9098 (1.21%) received a diagnosis of ASDs. We observed an increased risk of ASDs in the exposed children (IRR = 1.28, 1.11-1.47), especially for those who were exposed during the second trimester period (IRR = 1.38, 1.14-1.67). However, when extending the exposure time window to 1 year prior to pregnancy, we observed a similar association in children born to women who received beta2AA treatment during pregnancy (IRR = 1.33, 1.11-1.59) to that in children born to women who received beta2AA treatment 1 year prior to pregnancy (IRR = 1.35, 1.17-1.56). CONCLUSION : Our finding suggested that children born to women who used beta2AA during pregnancy have an increased risk of ASDs in later life, which is more likely due to underlying maternal diseases rather than the exposure to beta2AA itself. However, further study, which would better differentiate the effects between indication and medicine, is needed to corroborate the finding. Copyright (c) 2017 John Wiley & Sons, Ltd.
21. Sujan AC, Rickert ME, Oberg AS, Quinn PD, Hernandez-Diaz S, Almqvist C, Lichtenstein P, Larsson H, D’Onofrio BM. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA ;2017 (Apr 18) ;317(15):1553-1562.
Importance : Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective : To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants : This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures : Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures : Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results : Among 1580629 offspring (mean gestational age, 279 days ; 48.6% female ; 1.4% [n = 22544] with maternal first-trimester self-reported antidepressant use) born to 943776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55] ; small for gestational age OR, 1.15 [95% CI, 1.06-1.25] ; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26] ; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons. Conclusions and Relevance : Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
22. Tsao PC, Lee YS, Jeng MJ, Hsu JW, Huang KL, Tsai SJ, Chen MH, Soong WJ, Kou YR. Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder : a nationwide population-based longitudinal study. Eur Child Adolesc Psychiatry ;2017 (Apr 17)
In this retrospective nationwide population-based case-control study, we investigated the impact of congenital heart disease (CHD) on the development of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), which remains unclear. Children aged <18 years that were diagnosed with CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from the National Health Insurance Research Database in Taiwan. Non-CHD controls (n = 14,208) matched for age and sex (1:4) were selected from the same dataset. All subjects were observed until December 31, 2011 or their death. Comorbid perinatal conditions and early developmental disorders (EDD) that were diagnosed before ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the control group. Multivariate Cox regression analysis revealed that the CHD group had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95% confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after adjusting for confounding comorbidities. EDD, but not perinatal comorbidities were also independent risk factors for ADHD and ASD after adjustment. Subgroup analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD (HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD than in non-CHD subjects without EDD. These findings suggested that CHD at birth and EDD during early childhood were two independent risk factors for ADHD and ASD and that concurrent CHD and EDD might additively increase these risks.
23. Valenti D, de Bari L, Vigli D, Lacivita E, Leopoldo M, Laviola G, Vacca RA, De Filippis B. Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome. Neuropharmacology ;2017 (Apr 15)
Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that neurobehavioral and brain molecular alterations can be rescued in a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family, crucially involved in the regulation of brain structural plasticity and cognitive processes, can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective agonist. The present study extends previous findings by demonstrating that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial respiratory chain impairment, oxidative phosphorylation deficiency and the reduced energy status in the brain of heterozygous female mice from two highly validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211 treatment completely restored the radical species overproduction by brain mitochondria in the MeCP2-308 model and partially recovered the oxidative imbalance in the more severely affected MeCP2-Bird model. These results provide the first evidence that RTT brain mitochondrial dysfunction can be rescued targeting the brain serotonin receptor 7 and add compelling preclinical evidence of the potential therapeutic value of LP-211 as a pharmacological approach for this devastating neurodevelopmental disorder.
24. Vilidaite G, Yu M, Baker DH. Internal noise estimates correlate with autistic traits. Autism Res ;2017 (Apr 17)
Previous neuroimaging research has reported increased internal (neural) noise in sensory systems of autistic individuals. However, it is unclear if this difference has behavioural or perceptual consequences, as previous attempts at measuring internal noise in ASD psychophysically have been indirect. Here, we use a "gold standard" psychophysical double-pass paradigm to investigate the relationship between internal noise and autistic traits in the neurotypical population (n = 43). We measured internal noise in three tasks (contrast perception, facial expression intensity perception, and number summation) to estimate a global internal noise factor using principal components analysis. This global internal noise was positively correlated with autistic traits (rs = 0.32, P = 0.035). This suggests that increased internal noise is associated with the ASD phenotype even in subclinical populations. The finding is discussed in relation to the neural and genetic basis of internal noise in ASD. Autism Res 2017,. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
25. Westwood H, Mandy W, Simic M, Tchanturia K. Assessing ASD in Adolescent Females with Anorexia Nervosa using Clinical and Developmental Measures : a Preliminary Investigation. J Abnorm Child Psychol ;2017 (Apr 17)
The aim of this study was to use standardised, clinical assessment tools to explore the presence of Autism Spectrum Disorder (ASD) symptoms in a sample of adolescent females with Anorexia Nervosa (AN), receiving either day-patient or inpatient treatment for their eating disorder and to determine whether any such symptoms were present during the early developmental period, a requirement for a diagnosis of ASD. Using a cross-sectional design, 40 females aged between 12 and 18 were recruited from inpatient and day-patient eating disorder services. All participants had a diagnosis of AN and were assessed for symptoms of ASD using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2). If participants scored at or above clinical cut-off on the ADOS-2, their parents were asked to complete the Developmental, Dimensional and Diagnostic Interview, short version (3Di-sv). Of the 40 participants assessed, 21 scored above cut-off on the ADOS-2. When developmental history was obtained, only four participants scored above cut-off on all sub-scales of the 3Di-sv, thus meeting full research criteria for ASD. This study suggests that 10% of adolescents with AN from inpatient or day-patient settings may have diagnosable ASD, while a further 40% may show symptoms of ASD, which may arise from the ill-state of AN or are not supported by parental report.