1. Cunningham AB. {{Measuring Change in Social Interaction Skills of Young Children with Autism}}. {J Autism Dev Disord};2011 (Jun 3)
Designing effective treatments for improving early social behaviors in autism has been identified as a critical research need. One barrier to drawing conclusions about optimal treatments for children with autism is the use of highly varied dependent measures in the treatment literature. Contributing to this is the absence of « gold standard » assessment batteries. This is particularly true for assessing changes in social interaction impairments in very young children with autism. This paper addresses this issue by reviewing variables important in the development and evaluation of assessment measures, discussing previous studies’ choices of socially-related dependent measures, and the strengths, limitations, and research questions pertaining to them. It concludes with recommendations for measurement selection and future directions for research.
2. Foley KR, Downs J, Bebbington A, Jacoby P, Girdler S, Kaufmann WE, Leonard H. {{Change in Gross Motor Abilities of Girls and Women With Rett Syndrome Over a 3- to 4-Year Period}}. {J Child Neurol};2011 (Jun 2)
Rett syndrome is a rare but severe neurological disorder typically associated with a mutation in the MECP2 gene. We describe change in gross motor function over 3 to 4 years for 70 subjects participating in the Australian Rett Syndrome Database. Linear regression was used to assess relationships with age, genotype, and general and complex gross motor skills scores measured on the Gross Motor Scale for Rett syndrome. Skills were slightly better or maintained in approximately 40% of subjects and slightly decreased in approximately 60%. Teenagers and women who walked in 2004 were less likely to lose complex skills than those younger. Girls with a p.R294X mutation were more likely to lose complex motor skills, otherwise skill changes were spread across the mutation categories. In conclusion, small changes were observed over this period with greater stability of skills in teenagers and women with the ability to walk.
3. Herguner S, Kelesoglu FM, Tanidir C, Copur M. {{Ferritin and iron levels in children with autistic disorder}}. {Eur J Pediatr};2011 (Jun 4)
Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. Conclusion: These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.
4. Kagohara DM, Sigafoos J, Achmadi D, van der Meer L, O’Reilly MF, Lancioni GE. {{Teaching students with developmental disabilities to operate an iPod Touch((R)) to listen to music}}. {Res Dev Disabil};2011 (Jun 4)
We evaluated an intervention procedure for teaching three students with developmental disabilities to independently operate a portable multimedia device (i.e., an iPod Touch((R))) to listen to music. The intervention procedure included the use of video modeling, which was presented on the same iPod Touch((R)) that the students were taught to operate to listen to music. Four phases (i.e., baseline, intervention, fading, and follow-up) were arranged in accordance with a delayed multiple-probe across participants design. During baseline, the students performed from 25 to 62.5% of the task analyzed steps correctly. With intervention, all three students correctly performed 80-100% of the steps and maintained this level of performance when video modeling was removed and during follow-up. The findings suggest that the video modeling procedure was effective for teaching the students to independently operate a portable multimedia device to access age-appropriate leisure content.
5. Krajnc N, Zupancic N, Orazem J. {{Epilepsy Treatment in Rett Syndrome}}. {J Child Neurol};2011 (Jun 2)
Rett syndrome is a neurodevelopmental disorder predominately affecting females. The majority of patients have epilepsy in the early stages of the disease. This study evaluates the clinical course of epilepsy and the effect of antiepileptic drug treatment in Rett syndrome using retrospective data analysis. Epilepsy was present in 16 of 19 (84%) patients with Rett syndrome in this series. The mean age of seizure onset was 4 years. Remission of seizures was achieved after the first monotherapy in 56% and after the second monotherapy in 18.5% of patients. Valproate, lamotrigine, and carbamazepine were the drugs used most frequently as monotherapy. Valproate monotherapy was highly effective as 75% of treated patients achieved seizure remission. Monotherapy with lamotrigine or carbamazepine was effective in half of the treated patients. There was a clear tendency toward seizure remission after the age of 15 years.
6. Lukose R, Schmidt E, Wolski TP, Jr., Murawski NJ, Kulesza RJ, Jr. {{Malformation of the superior olivary complex in an animal model of autism}}. {Brain Res};2011 (May 13)
Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.
7. Motil KJ, Barrish JO, Lane J, Geerts SP, Annese F, McNair L, Percy AK, Skinner SA, Neul JL, Glaze DG. {{Vitamin D Deficiency is Prevalent in Females with Rett Syndrome}}. {J Pediatr Gastroenterol Nutr};2011 (May 30)
OBJECTIVES:: To determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D [25(OH)D] levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in females with Rett syndrome (RTT). STUDY DESIGN:: Retrospective review of the medical records of 284 females with RTT to determine serum 25(OH)D and parathyroid hormone levels, nutritional status, dietary sources of vitamin D, exposure to anticonvulsants, degree of mobility, and MECP2 status. RESULTS:: Twenty percent of females who were tested (n = 157) had 25(OH)D levels <50 nmol/L. Multivitamin supplements, vitamin D fortified milk, and commercial formulas were consumed by 40%, 52%, and 54%. Anticonvulsants were used by 57% and 39% ambulated independently. Median 25(OH)D levels were lower in individuals who did not receive multivitamin supplements (p < 0.05) or commercial formulas (p < 0.001) than in those who did. Median 25(OH)D levels differed (p < 0.01) among racial and ethnic groups, but the number in some groups was small. Nutritional status, use of anticonvulsants, degree of mobility, and MECP2 status did not influence 25(OH)D levels. CONCLUSION:: Vitamin D deficiency is prevalent in females with RTT. The use of multivitamin supplements or commercial formulas is associated with improved vitamin D levels. Attention to vitamin D may enhance bone mineral deposition and reduce the frequency of bone fractures in these individuals.
8. Oliveras-Rentas RE, Kenworthy L, Roberson RB, 3rd, Martin A, Wallace GL. {{WISC-IV Profile in High-Functioning Autism Spectrum Disorders: Impaired Processing Speed is Associated with Increased Autism Communication Symptoms and Decreased Adaptive Communication Abilities}}. {J Autism Dev Disord};2011 (Jun 3)
Changes in the Wechsler Intelligence Scales for Children-IV (WISC-IV) may affect the IQ profile characteristic of autism spectrum disorders (ASD). Moreover, the association of particular component cognitive abilities (unlike overall IQ) with symptomatology and adaptive functioning in ASD remains unclear. This archival study characterizes the WISC-IV IQ profile among 56 high-functioning (IQ > 70) children with ASD and correlates WISC-IV performance with ASD and ADHD symptomatology and adaptive functioning. The ASD WISC-IV profile included strengths on Matrix Reasoning and Similarities, weaknesses on Comprehension (which correlated negatively with social symptoms) and the subtests comprising the Processing Speed Index (Coding, Symbol Search). Processing speed task performance correlated negatively with communication symptoms and positively with communication abilities, indicating its importance to functional outcomes in ASD.
9. Pacey LK, Tharmalingam S, Hampson DR. {{Subchronic Administration and Combination Metabotropic Glutamate and GABAB Receptor Drug Therapy in Fragile X Syndrome}}. {J Pharmacol Exp Ther};2011 (Jun 2)
The most common cause of inherited mental retardation, Fragile X Syndrome (FXS), results from a triplet repeat expansion in the FMR1 gene and loss of the mRNA binding protein, fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through Group I metabotropic glutamate receptors (mGluRs) is enhanced. We previously proposed a mechanism whereby the audiogenic seizures exhibited by FMR1 null mice result from an imbalance in excitatory mGluR and inhibitory GABAB receptor signaling (Pacey et al., 2009). Here we tested the mGluR5 positive allosteric modulator CDPPB, the mGluR5 inverse agonist MPEP, and GABAB receptor agonists, alone and in combination on receptor protein expression and audiogenic seizures in FMR1 mice. Single doses of MPEP (30 mg/kg), the GABABR orthosteric agonist R-baclofen (1 mg/kg), or the GABABR positive allosteric modulator GS-39783 (30 mg/kg), reduced the incidence of seizures. However, when administered subchronically (daily injections for 6 days), MPEP retained its anticonvulsant activity while R-baclofen and GS-39783 did not. When administered at lower doses that had no effect when given alone, a single injection of MPEP plus R-baclofen also reduced seizures, but the effect was lost after subchronic administration. Surprisingly, subchronic treatment with R-baclofen also induced tolerance to a single high dose of MPEP. These data demonstrate that tolerance develops rapidly to the anti-seizure properties of R-baclofen alone and R-baclofen co-administered with MPEP, but not with MPEP alone. Our findings suggest that cross-talk between the G-protein signaling pathways of these receptors affects drug efficacy after repeated treatment.
10. Shandal V, Sundaram SK, Chugani DC, Kumar A, Behen ME, Chugani HT. {{Abnormal Brain Protein Synthesis in Language Areas of Children With Pervasive Developmental Disorder: A L-[1-11C]-Leucine PET Study}}. {J Child Neurol};2011 (Jun 2)
This study was performed to evaluate the cerebral protein synthesis rate of language brain regions in children with developmental delay with and without pervasive developmental disorder. The authors performed L-[1-(11)C]-leucine positron emission tomography (PET) on 8 developmental delay children with pervasive developmental disorder (mean age, 76.25 months) and 8 developmental delay children without pervasive developmental disorder (mean age, 77.63 months). They found a higher protein synthesis rate in developmental delay children with pervasive developmental disorder in the left posterior middle temporal region (P = .014). There was a significant correlation of the Gilliam Autism Rating Scale autism index score with the protein synthesis rate of the left posterior middle temporal region (r = .496, P = .05). In addition, significant asymmetric protein synthesis (right > left) was observed in developmental delay children without pervasive developmental disorder in the middle frontal and posterior middle temporal regions (P = .03 and P = .04, respectively). In conclusion, abnormal language area protein synthesis in developmentally delayed children may be related to pervasive symptoms.
11. Suda M, Takei Y, Aoyama Y, Narita K, Sakurai N, Fukuda M, Mikuni M. {{Autistic Traits and Brain Activation during Face-to-Face Conversations in Typically Developed Adults}}. {PLoS One};2011;6(5):e20021.
BACKGROUND: Autism spectrum disorders (ASD) are characterized by impaired social interaction and communication, restricted interests, and repetitive behaviours. The severity of these characteristics is posited to lie on a continuum that extends into the general population. Brain substrates underlying ASD have been investigated through functional neuroimaging studies using functional magnetic resonance imaging (fMRI). However, fMRI has methodological constraints for studying brain mechanisms during social interactions (for example, noise, lying on a gantry during the procedure, etc.). In this study, we investigated whether variations in autism spectrum traits are associated with changes in patterns of brain activation in typically developed adults. We used near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technique that uses near-infrared light, to monitor brain activation in a natural setting that is suitable for studying brain functions during social interactions. METHODOLOGY: We monitored regional cerebral blood volume changes using a 52-channel NIRS apparatus over the prefrontal cortex (PFC) and superior temporal sulcus (STS), 2 areas implicated in social cognition and the pathology of ASD, in 28 typically developed participants (14 male and 14 female) during face-to-face conversations. This task was designed to resemble a realistic social situation. We examined the correlations of these changes with autistic traits assessed using the Autism-Spectrum Quotient (AQ). PRINCIPAL FINDINGS: Both the PFC and STS were significantly activated during face-to-face conversations. AQ scores were negatively correlated with regional cerebral blood volume increases in the left STS during face-to-face conversations, especially in males. CONCLUSIONS: Our results demonstrate successful monitoring of brain function during realistic social interactions by NIRS as well as lesser brain activation in the left STS during face-to-face conversations in typically developed participants with higher levels of autistic traits.
