1. Atladottir HO, Henriksen TB, Schendel DE, Parner ET. {{Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study}}. {Pediatrics}. 2012.
OBJECTIVES:Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring.METHODS:We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD.RESULTS:Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.CONCLUSIONS:Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.
Lien vers le texte intégral (Open Access ou abonnement)
2. Balestrieri E, Arpino C, Matteucci C, Sorrentino R, Pica F, Alessandrelli R, Coniglio A, Curatolo P, Rezza G, Macciardi F, Garaci E, Gaudi S, Sinibaldi-Vallebona P. {{HERVs Expression in Autism Spectrum Disorders}}. {PLoS One}. 2012; 7(11): e48831.
BACKGROUND: Autistic Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder, resulting from complex interactions among genetic, genomic and environmental factors. Here we have studied the expression of Human Endogenous Retroviruses (HERVs), non-coding DNA elements with potential regulatory functions, and have tested their possible implication in autism. METHODS: The presence of retroviral mRNAs from four HERV families (E, H, K and W), widely implicated in complex diseases, was evaluated in peripheral blood mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV-H, HERV-W and HERV-K families in PBMCs at the time of sampling and after stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR. Differences between groups were evaluated using statistical methods. RESULTS: The percentage of HERV-H and HERV-W positive samples was higher among ASD patients compared to HCs, while HERV-K was similarly represented and HERV-E virtually absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W are differentially expressed in the two groups, with HERV-H being more abundantly expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs compared to healthy controls. PMBCs from ASDs also showed an increased potential to up-regulate HERV-H expression upon stimulation in culture, unlike HCs. Furthermore we report a negative correlation between expression levels of HERV-H and age among ASD patients and a statistically significant higher expression in ASD patients with Severe score in Communication and Motor Psychoeducational Profile-3. CONCLUSIONS: Specific HERV families have a distinctive expression profile in ASD patients compared to HCs. We propose that HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder.
Lien vers le texte intégral (Open Access ou abonnement)
3. Ben-David E, Shifman S. {{Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism}}. {Mol Psychiatry}. 2012.
Lien vers le texte intégral (Open Access ou abonnement)
4. Estes A, Olson E, Sullivan K, Greenson J, Winter J, Dawson G, Munson J. {{Parenting-related stress and psychological distress in mothers of toddlers with autism spectrum disorders}}. {Brain Dev}. 2012.
Background:Parents of children with autism spectrum disorders (ASDs) are at risk for higher stress levels than parents of children with other developmental disabilities and typical development. Recent advances in early diagnosis have resulted in younger children being diagnosed with ASDs but factors associated with parent stress in this age group are not well understood. Aims: The present study examined parenting-related stress and psychological distress in mothers of toddlers with ASD, developmental delay without ASD (DD), and typical development. The impact of child problem behavior and daily living skills on parenting-stress and psychological distress were further investigated. Methods: Participants were part of a larger research study on early ASD intervention. Results: Parent self-report of parenting-related stress and psychological distress was utilized. Parents of toddlers with ASD demonstrated increased parenting-related stress compared with parents of toddlers with DD and typical development. However, psychological distress did not differ significantly between the groups. Child behavior problems, but not daily living skills emerged as a significant predictor of parenting-related stress and psychological distress. This was true for both mothers of children with ASD and DD. Conclusions: These finding suggest that parents’ abilities to manage and reduce behavior problems is a critical target for interventions for young children with ASD and DD in order to improve child functioning and decrease parenting-related stress.
Lien vers le texte intégral (Open Access ou abonnement)
5. Kim SY, Burris J, Bassal F, Koldewyn K, Chattarji S, Tassone F, Hessl D, Rivera SM. {{Fear-Specific Amygdala Function in Children and Adolescents on the Fragile X Spectrum: A Dosage Response of the FMR1 Gene}}. {Cereb Cortex}. 2012.
Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
6. McDougle CJ, Carlezon WA, Jr. {{Neuroinflammation and autism: toward mechanisms and treatments}}. {Neuropsychopharmacology}. 2013; 38(1): 241-2.
Lien vers le texte intégral (Open Access ou abonnement)
7. Paul K, Venkitaramani D, Cox C. {{Dampened dopamine-mediated neuromodulation in prefrontal cortex of Fragile X mice}}. {J Physiol}. 2012.
FFragile X Syndrome (FXS) is the most common form of inheritable mental retardation caused by transcriptional silencing of the Fmr1 gene resulting in the absence of fragile X mental retardation protein (FMRP). The role of this protein in neurons is complex and its absence gives rise to diverse alterations in neuronal function leading to neurological disorders including mental retardation, hyperactivity, cognitive impairment, obsessive-compulsive behavior, seizure activity, and autism. FMRP regulates mRNA translation at dendritic spines where synapses are formed, and thus, the lack of FMRP can lead to disruptions in synaptic transmission and plasticity. Many of these neurological deficits in FXS likely involve the prefrontal cortex, and in this study, we have focused on modulatory actions of dopamine (DA) in the medial prefrontal cortex (mPFC). Our data shows that dopamine produces a long-lasting enhancement of evoked inhibitory postsynaptic currents (IPSCs) mediated by D1 type receptors seen in wild type (WT) mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice. The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show significant disruption of dopaminergic modulation of synaptic transmission in the Fmr1 KO mice and this alteration in inhibitory activity may provide insight into potential targets for the rescue of deficits associated with FXS.
Lien vers le texte intégral (Open Access ou abonnement)
8. Power RA, Kyaga S, Uher R, Maccabe JH, Langstrom N, Landen M, McGuffin P, Lewis CM, Lichtenstein P, Svensson AC. {{Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings}}. {Arch Gen Psychiatry}. 2012: 1-8.
CONTEXT It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants. OBJECTIVES To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants. DESIGN We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population. SETTING Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register. PARTICIPANTS In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden. MAIN OUTCOME MEASURES Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status. RESULTS Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals. CONCLUSIONS Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.
Lien vers le texte intégral (Open Access ou abonnement)
9. Ryland HK, Hysing M, Posserud MB, Gillberg C, Lundervold AJ. {{Autism spectrum symptoms in children with neurological disorders}}. {Child Adolesc Psychiatry Ment Health}. 2012; 6(1): 34.
ABSTRACT: BACKGROUND: The aims of the present study were to assess symptoms associated with an autism spectrum disorder (ASD) in children with neurological disorders as reported by parents and teachers on the Autism Spectrum Screening Questionnaire (ASSQ), as well the as the level of agreement between informants for each child. METHODS: The ASSQ was completed by parents and teachers of the 5730 children (11–13 years) who participated in the second wave of the Bergen Child Study (BCS), an on-going longitudinal population-based study. Out of these children, 496 were reported to have a chronic illness, including 99 whom had a neurological disorder. The neurological disorder group included children both with and without intellectual disabilities. RESULTS: Children with neurological disorders obtained significantly higher parent and teacher reported ASSQ scores than did non-chronically ill children and those with other chronic illnesses (p<.01; ES = .50-1.01), and 14.1 % were screened above the positive cutoff score for ASD according to their combined parent and teacher ASSQ scores. Parent/teacher agreement over ASSQ scores for children with neurological disorders was moderate to high for the total score and for three sub scores generated from a factor analysis, and low to moderate for single items. CONCLUSIONS: The ASSQ identifies a high rate of ASD symptoms in children with neurological disorders, and a large number of children screened in the positive range for ASD. Although a firm conclusion awaits further clinical studies, the present results suggest that health care professionals should be aware of potential ASD related problems in children with neurological disorders, and should consider inclusion of the ASSQ or similar screening instruments as part of their routine assessment of this group.
