1. Andersen CH, Thomsen PH, Nohr EA, Lemcke S. {{Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children}}. {Eur Child Adolesc Psychiatry};2017 (Jul 15)
The risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) may be influenced by environmental factors such as maternal obesity before pregnancy. Previous studies investigating those associations have found divergent results. We aim to investigate in a large birth cohort this association further in children with ADHD, ASD and comorbid ADHD and ASD. Our study population consisted of 81,892 mother-child pairs participating in the Danish National Birth Cohort (DNBC). Information about pre-pregnancy weight and height was collected in week 16 of pregnancy; the analysis was divided into groups based on BMI. Children with a clinical diagnosis of ADHD and/or ASD were identified in the Danish health registries at an average age of 13.3 years. Hazard ratios (HRs) were estimated using time-to-event analysis. Compared to normal weight mothers, the risk of having a child with ADHD was significantly increased if the mother was overweight (HR = 1.28 [95% CI 1.15;1.48]), obese (HR = 1.47 [95% CI 1.26;1.71]) or severely obese (HR = 1.95 [95% CI 1.58;2.40]). The same pattern was seen for the combined ADHD and ASD group. Regarding ASD, an increased risk was observed in underweight (HR = 1.30 [95% CI 1.01;1.69]) and obese (HR = 1.39 [95% CI 1.11;1.75]) mothers. Subgroup analysis revealed that the association in the ADHD group could mostly be attributable to the hyperactive group. Maternal obesity before pregnancy is a risk factor for ADHD in children. Maternal obesity as well as underweight may also be associated with an increased risk for ASD.
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2. Backer van Ommeren T, Koot HM, Begeer S. {{Reciprocity in autistic and typically developing children and adolescents with and without mild intellectual disabilities}}. {J Intellect Disabil Res};2017 (Aug);61(8):810-817.
The assessment of autism in individuals with mild intellectual disabilities (MID) is complicated because of the overlap between autistic traits and intellectual limitations. Impaired social emotional reciprocity is a core diagnostic criterion for autism. However, it is unknown whether reciprocal behaviour differs between MID individuals with or without an autism spectrum disorder (ASD). This study explored differences in reciprocal behaviour of 35 children and adolescents with MID (intelligence quotient 50-85): 15 with ASD (ASD-MID) and 20 with typical development (TD-MID) using the Interactive Drawing Test (IDT). ASD-MID participants showed a lower quality of reciprocal behaviour compared with TD-MID participants. The difference in quality of reciprocal behaviour between ASD-MID and TD-MID participants was not significantly related with Peabody Picture Vocabulary Test scores and thus not attributable to verbal capacity. The IDT is likely to reflect the child’s inclination to display reciprocal behaviour in everyday situations, as its scale scores were meaningfully associated with the level of social cognition assessed with the Social Responsiveness Scale. Thus, the IDT seems well suited for measuring impairments in reciprocal behaviour in children and adolescents with MID.
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3. Carlisi CO, Norman LJ, Lukito SS, Radua J, Mataix-Cols D, Rubia K. {{Comparative Multimodal Meta-analysis of Structural and Functional Brain Abnormalities in Autism Spectrum Disorder and Obsessive-Compulsive Disorder}}. {Biol Psychiatry};2017 (Jul 15);82(2):83-102.
BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped and repetitive and compulsive behaviors, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions. METHODS: A comparative meta-analysis of 62 voxel-based morphometry and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing gray matter volume and activation abnormalities between patients with ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and control subjects. Multimodal meta-analysis compared groups across voxel-based morphometry and fMRI. RESULTS: Both disorders shared reduced function and structure in the rostral and dorsomedial prefrontal cortex including the anterior cingulate. OCD patients had a disorder-specific increase in structure and function of left basal ganglia (BG) and insula relative to control subjects and ASD patients, who had reduced right BG and insula volumes versus OCD patients. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, whereas OCD patients showed temporoparietal underactivation. CONCLUSIONS: The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. Whereas the rostrodorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG and insula in OCD patients, but a reduction in ASD patients, presumably reflecting a disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor frontal control over overactive BG, and a frontostriatoinsular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in patients with ASD and OCD.
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4. Harris A, Williams JM. {{The Impact of a Horse Riding Intervention on the Social Functioning of Children with Autism Spectrum Disorder}}. {Int J Environ Res Public Health};2017 (Jul 14);14(7)
This paper reports a case-control study of a horse riding intervention for children with autism spectrum disorder (ASD). A sample of 26 children, aged 6 to 9 years, were assigned to either the intervention (n = 12) or control group conditions (n = 14). Pre- and post-tests were carried out using the Childhood Autism Rating Scale, Second Edition (CARS2) and the Aberrant Behaviour Checklist-Community Edition (ABC-C). An observational measure of compliance and behaviour during the horse riding sessions was completed for the intervention group. There was a significant reduction in the severity of ASD symptoms and hyperactivity from pre- to post-test for the intervention group only. These results indicate that the intervention improves some aspects of social functioning for children with ASD.
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5. Hodges JL, Yu X, Gilmore A, Bennett H, Tjia M, Perna JF, Chen CC, Li X, Lu J, Zuo Y. {{Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome}}. {Biol Psychiatry};2017 (Jul 15);82(2):139-149.
BACKGROUND: Fragile X syndrome (FXS) is the most common type of mental retardation attributable to a single-gene mutation. It is caused by FMR1 gene silencing and the consequent loss of its protein product, fragile X mental retardation protein. Fmr1 global knockout (KO) mice recapitulate many behavioral and synaptic phenotypes associated with FXS. Abundant evidence suggests that astrocytes are important contributors to neurological diseases. This study investigates astrocytic contributions to the progression of synaptic abnormalities and learning impairments associated with FXS. METHODS: Taking advantage of the Cre-lox system, we generated and characterized mice in which fragile X mental retardation protein is selectively deleted or exclusively expressed in astrocytes. We performed in vivo two-photon imaging to track spine dynamics/morphology along dendrites of neurons in the motor cortex and examined associated behavioral defects. RESULTS: We found that adult astrocyte-specific Fmr1 KO mice displayed increased spine density in the motor cortex and impaired motor-skill learning. The learning defect coincided with a lack of enhanced spine dynamics in the motor cortex that normally occurs in response to motor skill acquisition. Although spine density was normal at 1 month of age in astrocyte-specific Fmr1 KO mice, new spines formed at an elevated rate. Furthermore, fragile X mental retardation protein expression in only astrocytes was insufficient to rescue most spine or behavioral defects. CONCLUSIONS: Our work suggests a joint astrocytic-neuronal contribution to FXS pathogenesis and reveals that heightened spine formation during adolescence precedes the overabundance of spines and behavioral defects found in adult Fmr1 KO mice.
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6. Kuiper MWM, Verhoeven EWM, Geurts HM. {{Heart rate variability predicts inhibitory control in adults with autism spectrum disorders}}. {Biol Psychol};2017 (Jul 15)
Several studies suggest that inhibition difficulties among people with ASD might be related to atypical cardiac vagal control. We examined how low versus high baseline heart rate variability (HRV) influences prepotent response inhibition in 31 males with autism spectrum disorder (ASD; mean age: 32.2; mean IQ: 107.8) compared to 39 typically developing (TD) males (mean age: 30.5; mean IQ: 102.0) by administering a stop signal task. Moreover, we examined whether adding an affective manipulation would alter findings and whether this manipulation affected HRV. Findings indicated that baseline HRV influenced inhibition in ASD males. Specifically, an ASD subgroup with low baseline HRV performed significantly worse compared to an ASD subgroup with high baseline HRV. No influence of baseline HRV was found in TD males. The affective manipulation did negatively influence performance and also altered HRV. Although replication is required, these first findings indicate that baseline cardiac vagal control seems to affect inhibitory control in males with ASD.
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7. Lashewicz BM, Shipton L, Lien K. {{Meta-synthesis of fathers’ experiences raising children on the autism spectrum}}. {J Intellect Disabil};2017 (Jan 01):1744629517719347.
Parents raising children with autism have distinct experiences that influence their well-being, relationships, engagement with the public, and interaction with education and healthcare systems. However, experiences of fathers of children with autism have been largely overlooked by researchers. This meta-synthesis is our synthesis of qualitative accounts of fathers’ experiences and we included peer reviewed and gray literature articles that: (1) reported primary qualitative research, (2) included fathers of children with autism as participants, and (3) reported qualitative findings on the first-hand experiences of fathers of children with autism. Studies were appraised for quality and many theoretical and methodological deficiencies identified. Six studies met quality appraisal criteria and three main themes of findings from these studies were generated: (1) adaptation and concern with the future, (2) the importance of cultural context, and (3) reverence for one’s child and new opportunities. Fathers’ experiences illuminate a need for father-oriented resources that recognize fathers’ value in children’s lives.
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8. Ptomey LT, Willis EA, Lee J, Washburn RA, Gibson CA, Honas JJ, Donnelly JE. {{The feasibility of using pedometers for self-report of steps and accelerometers for measuring physical activity in adults with intellectual and developmental disabilities across an 18-month intervention}}. {J Intellect Disabil Res};2017 (Aug);61(8):792-801.
BACKGROUND: Improving physical activity in adults with intellectual and developmental disabilities (IDDs) is recommended to improve weight loss and general health. However, in order to determine the success of physical activity interventions, identification of feasible methods for assessment of physical activities is necessary. The purpose of this study is to assess the feasibility of adults with IDD to track daily steps and wear an accelerometer. METHODS: Overweight/obese adults with mild to moderate IDD followed a diet and physical activity program for 18 months. All participants were asked to wear a pedometer and track steps daily by using a pedometer and to provide accelerometer data for 7 days at baseline, 6, 12 and 18 months. Adherence to the pedometer protocol and plausibility of the number of recorded steps were assessed, and these measures along with average wear time of the accelerometer were recorded. RESULTS: Data were collected from 149 participants (36.5 +/- 12.2 years of age, 57% female). Participants recorded a step value on 81.5% of days across the 18-month study, with 40.9% of written days classified as plausible. When wearing the accelerometer, 26.8% of participants met the recommended 4-day/10-h wear time criterion at baseline, and 22.6, 24.8 and 18.8% met the criterion at 6, 12 and 18 months, respectively. CONCLUSIONS: Adults with IDD will adhere reasonably well to wearing a pedometer long term, but may be unable to record the step data accurately. Furthermore, adults with IDD have poor compliance with accelerometer protocols, and future studies should determine if a shorter wear time protocol would produce valid data in this population.
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9. Soghomonian JJ, Zhang K, Reprakash S, Blatt GJ. {{Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism}}. {Autism Res};2017 (Jul 14)
Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez-Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin-expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post-mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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10. 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 (Jul 15);121:79-88.
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 5-HT7R and add compelling preclinical evidence of the potential therapeutic value of LP-211 as a pharmacological approach for this devastating neurodevelopmental disorder.
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11. Wang JY, Trivedi AM, Carrillo NR, Yang J, Schneider A, Giulivi C, Adams P, Tassone F, Kim K, Rivera SM, Lubarr N, Wu CY, Irwin RW, Brinton RD, Olichney JM, Rogawski MA, Hagerman RJ. {{Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome}}. {Neurotherapeutics};2017 (Jul 13)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks. All patients completed baseline and follow-up studies, though MRI scans were not collected from 1 patient because of MRI contraindications. The MRI scans from previous visits, along with scans from 8 age-matched male controls, were also included to establish patients’ baseline condition as a reference. Functional outcomes included quantitative measurements of tremor and ataxia and neuropsychological evaluations. Brain activity consisted of event-related potential N400 word repetition effect during a semantic memory processing task. Structural MRI outcomes comprised volumes of the hippocampus, amygdala, and fluid-attenuated inversion recovery hyperintensities, and microstructural integrity of the corpus callosum. The results of the study showed that allopregnanolone infusions were well tolerated in all subjects. Before treatment, the patients disclosed impairment in executive function, verbal fluency and learning, and progressive deterioration of all MRI measurements. After treatment, the patients demonstrated improvement in executive functioning, episodic memory and learning, and increased N400 repetition effect amplitude. Although MRI changes were not significant as a group, both improved and deteriorated MRI measurements occurred in individual patients in contrast to uniform deterioration before the treatment. Significant correlations between baseline MRI measurements and changes in neuropsychological test scores indicated the effects of allopregnanolone on improving executive function, learning, and memory for patients with relatively preserved hippocampus and corpus callosum, while reducing psychological symptoms for patients with small hippocampi and amygdalae. The findings show the promise of allopregnanolone in improving cognitive functioning in patients with FXTAS and in partially alleviating some aspects of neurodegeneration. Further studies are needed to verify the efficacy of allopregnanolone for treating FXTAS.
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12. Wikramanayake M, Mandy W, Shahper S, Kaur S, Kolli S, Osman S, Reid J, Jefferies Sewell K, Fineberg N. {{Autism Spectrum Disorders in Adult Outpatients with Obsessive Compulsive Disorder in the UK}}. {Int J Psychiatry Clin Pract};2017 (Jul 14):1-22.
BACKGROUND: Patients with obsessive compulsive disorder (OCD) frequently show traits of autism spectrum disorders (ASD). This is one of the first studies to explore the clinical impact of the overlap between OCD and ASD as a categorical diagnosis. METHODS: A cross-sectional survey in 73 adult outpatients with DSM-IV OCD. Autistic traits were measured using the Autism-Spectrum Quotient (AQ). A clinical estimate ASD diagnosis was made by interview using DSM-IV-TR criteria. OCD patients with and without autistic traits or ASD were compared on demographic and clinical parameters and level of OCD treatment-resistance based on treatment history. RESULTS: Thirty-four (47%) patients scored above the clinical threshold on the AQ (> =26) and 21 (27.8%) met diagnostic criteria for ASD. These diagnoses had not been made before. Patients with autistic traits showed a borderline significant increase in OCD symptom-severity (Yale-Brown Obsessive Compulsive Scale (Y-BOCS); p=.054) and significantly increased impairment of insight (Brown Assessment of Beliefs Scale; p=.01). There was a positive correlation between AQ and Y-BOCS scores (p =.04), but not with OCD treatment resistance. CONCLUSION: There is a high prevalence of previously undiagnosed ASD in patients with OCD. ASD traits are associated with greater OCD symptom-severity and poor insight.
