1. Adams NC, Jarrold C. {{Inhibition and the validity of the Stroop task for children with autism}}.{ J Autism Dev Disord};2009 (Aug);39(8):1112-1121.
Findings are mixed concerning inhibition in autism. Using the classic Stroop, children with autism (CWA) often outperform typically developing children (TDC). A classic Stroop and a chimeric animal Stroop were used to explore the validity of the Stroop task as a test of inhibition for CWA. During the classic Stroop, children ignored the word and named the ink colour, then vice versa. Although CWA showed less interference than TDC when colour naming, both groups showed comparable interference when word reading. During the chimeric animal task, children ignored bodies of animals and named heads, and vice versa; the groups performed comparably. Findings confirm that lower reading comprehension affects Stroop interference in CWA, potentially leading to inaccurate conclusions concerning inhibition in CWA.
2. Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET. {{Association of family history of autoimmune diseases and autism spectrum disorders}}. {Pediatrics};2009 (Aug);124(2):687-694.
OBJECTIVES: Recent studies suggest that familial autoimmunity plays a part in the pathogenesis of ASDs. In this study we investigated the association between family history of autoimmune diseases (ADs) and ASDs/infantile autism. We perform confirmatory analyses based on results from previous studies, as well as various explorative analyses. METHODS: The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression. RESULTS: A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Increased risk of ASDs was observed for children with a maternal history of rheumatoid arthritis and celiac disease. Also, increased risk of infantile autism was observed for children with a family history of type 1 diabetes. CONCLUSIONS: Associations regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASDs were confirmed from previous studies. A significant association between maternal history of celiac disease and ASDs was observed for the first time. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.
3. Benjak T, Vuletic Mavrinac G, Pavic Simetin I. {{Comparative study on self-perceived health of parents of children with autism spectrum disorders and parents of non-disabled children in Croatia}}. {Croat Med J};2009 (Aug);50(4):403-409.
AIM: To assess self-perceived health of parents of children with autism spectrum disorders (ASD) in comparison with those of parents of non-disabled children. METHODS: A total of 350 parents participated in the study: 178 parents of children with ASD (71% response rate) and 172 parents of non-disabled children matched by age, education, and place of living. Parents’ self-perceived health was assessed using the Croatian version of the health status questionnaire SF-36, while socio-demographic information, chronic medical conditions, and needs were assessed by a general questionnaire. RESULTS: For all dimensions of health, except physical health, parents of children with ASD had significantly poorer self-perceived health and reported significantly more deteriorated health in the last year than the control group (P<0.001). They also reported more psychological disorders (11% vs 4.3%), which was the largest difference in specified chronic medical conditions. Hundred twenty six (71%) parents of children with ASD thought that enhancing different policy measures (economic, social, educational) could advance their and their children’s health and well-being. CONCLUSION: Parents of children with ASD had poorer health than the control group in all components, except physical health. Because parents are the main providers of support for children with ASD, preserving parents’ good health and well-being is a precondition for an optimal care for children. Therefore, current system for treating children with ASD in Croatia should also include permanent improvement of parents’ health and well-being.
4. Bent S, Bertoglio K, Hendren RL. {{Omega-3 fatty acids for autistic spectrum disorder: a systematic review}}. {J Autism Dev Disord};2009 (Aug);39(8):1145-1154.
We conducted a systematic review to determine the safety and efficacy of omega-3 fatty acids for autistic spectrum disorder (ASD). Articles were identified by a search of MEDLINE, EMBASE, and the Cochrane Database using the terms autism or autistic and omega-3 fatty acids. The search identified 143 potential articles and six satisfied all inclusion criteria. One small randomized controlled trial (n = 13) noted non-significant improvements in hyperactivity and stereotypy. The remaining five studies were small (n = 30, 22, 19, 9, and 1) with four reporting improvements in a wide range of outcomes including language and learning skills, parental observations of general health and behavior, a clinician-administered symptom scale, and clinical observations of anxiety. Due to the limitations of evidence from uncontrolled studies and the presence of only one small randomized controlled trial, there is currently insufficient scientific evidence to determine if omega-3 fatty acids are safe or effective for ASD.
5. Benvenuto A, Moavero R, Alessandrelli R, Manzi B, Curatolo P. {{Syndromic autism: causes and pathogenetic pathways}}. {World J Pediatr};2009 (Aug);5(3):169-176.
BACKGROUND: Autism is a severe neurodevelopmental disorder known to have many different etiologies. In the last few years, significant progresses have been made in comprehending the causes of autism and their multiple impacts on the developing brain. This article aims to review the current understanding of the etiologies and the multiple pathogenetic pathways that are likely to lead to the autistic phenotype. DATA SOURCES: The PubMed database was searched with the keywords « autism » and « chromosomal abnormalities », « metabolic diseases », « susceptibility loci ». RESULTS: Genetic syndromes, defined mutations, and metabolic diseases account for less than 20% of autistic patients. Alterations of the neocortical excitatory/inhibitory balance and perturbations of interneurons’ development represent the most probable pathogenetic mechanisms underlying the autistic phenotype in fragile X syndrome and tuberous sclerosis complex. Chromosomal abnormalities and potential candidate genes are strongly implicated in the disruption of neural connections, brain growth and synaptic/dendritic morphology. Metabolic and mitochondrial defects may have toxic effects on the brain cells, causing neuronal loss and altered modulation of neurotransmission systems. CONCLUSIONS: A wide variety of cytogenetic abnormalities have been recently described, particularly in the low functioning individuals with dysmorphic features. Routine metabolic screening studies should be performed in the presence of autistic regression or suggestive clinical findings. As etiologies of autism are progressively discovered, the number of individuals with idiopathic autism will progressively shrink. Studies of genetic and environmentally modulated epigenetic factors are beginning to provide some clues to clarify the complexities of autism pathogenesis. The role of the neuropediatrician will be to understand the neurological basis of autism, and to identify more homogenous subgroups with specific biologic markers.
6. Briegel W, Schimek M, Kamp-Becker I, Hofmann C, Schwab KO. {{Autism spectrum disorders in children and adolescents with Moebius sequence}}. {Eur Child Adolesc Psychiatry};2009 (Aug);18(8):515-519.
Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups. The primary caregivers of all children and adolescents with Moebius sequence aged 6-17 years known to the German Moebius foundation were anonymously asked to complete two screening measures of ASD [Behavior and Communication Questionnaire (VSK); Marburger Asperger’s Syndrome Rating Scale (MBAS)]. For those who reached the cut-off for ASD, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, WISC-III, and Kinder-DIPS) should be administered. Minimal diagnostic criteria for Moebius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Familiar cases should be excluded. The primary caregivers of 35/46 children and adolescents (18 males, 17 females, mean age 11.5 years) sent back completed questionnaires, but only 27 subjects met inclusion criteria. According to the primary caregivers, none of these subjects showed mental retardation. Two probands (both males 9 and 16 years old) reached the cut-off of the MBAS whereas the results of the VSK did not indicate ASDs in any of the patients. The 9 year old boy could be examined personally and did not meet diagnostic criteria of ASD. ASDs might be not as frequent as reported in previous studies on patients with Moebius sequence, at least not in patients without mental retardation.
7. Broderick AA. {{Autism, « Recovery (to Normalcy), » and the Politics of Hope}}. {Intellect Dev Disabil};2009 (Aug);47(4):263-281.
This article draws on the traditions of critical discourse analysis (N. Fairclough, 1995, 2001; M. Foucault, 1972, 1980; J. P. Gee, 1999) in critically examining the discursive formation of « recovery » from autism in applied behavioral analysis (ABA) discourse and its relationship to constructs of hope. Constituted principally in the work of O. I. Lovaas (1987) and C. Maurice (1993), and central to ABA discourse on recovery, has been the construction of a particular vision of hope that has at least 2 integral conceptual elements: (a) Hope for recovery within ABA discourse is constructed in binary opposition to hopelessness, and (b) recovery within ABA discourse is discursively constructed as « recovery (to normalcy). » The author analyzes these 2 pivotal ABA texts within the context of an analysis of other uses of the term recovery in broader bodies of literature: (a) within prior autism-related literature, particularly autobiography, and (b) within literature emanating from the psychiatric survivors’ movement. If, indeed, visions of hope inform educational policy and decision making, this analysis addresses S. Danforth’s (1997) cogent query, « On what basis hope? », and asserts that moral and political commitments should be central sources of visions of hope and, therefore, inform educational policy and decision making for young children with labels of autism.
8. Brosnan M, Turner-Cobb J, Munro-Naan Z, Jessop D. {{Absence of a normal cortisol awakening response (CAR) in adolescent males with Asperger syndrome (AS)}}. {Psychoneuroendocrinology};2009 (Aug);34(7):1095-1100.
In addition to abnormalities in social and communication development, a ‘need for sameness’ and ‘resistance to change’ are features of autistic spectrum disorders first identified by Kanner in 1943. Our ability to react to change is modulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feature of which is a dramatic increase in cortisol upon waking, the Cortisol Awakening Response (CAR). This study examined whether the CAR was evident in 20 adolescent males with Asperger Syndrome (AS) and 18 age-matched typically developing (TD) controls (aged 11-16). Whilst a significant CAR was evidenced in the TD control group, this was not the case for those with AS. A normal diurnal decrease in cortisol, however, was evident in both groups. The implication that individuals with AS may have an impaired response to change in their environment due to a refractory HPA axis is discussed.
9. Burke LM, Kalpakjian CZ, Smith YR, Quint EH. {{Gynecologic Issues of Adolescents with Down Syndrome, Autism, and Cerebral Palsy}}. {J Pediatr Adolesc Gynecol};2009 (Jul 28)
STUDY OBJECTIVE: The gynecologic issues of adolescents with disabilities are understudied. The purpose of this study was to identify and compare the presenting complaints, treatments, and follow-up of adolescent girls with Down syndrome (DS), autism, and cerebral palsy (CP) presenting to a specialized gynecologic clinic for women with developmental disabilities. SETTING: Outpatient gynecology clinic. PARTICIPANTS: Forty four adolescents (<21 y); 13 with DS, 14 with autism, and 17 with CP who presented to the clinic from 1999 to 2006. INTERVENTIONS: None. MAIN OUTCOME MEASURES: A retrospective review of the electronic medical records to collect data on age at presentation to clinic, ethnicity, menstrual history, chief complaint, treatment, and follow-up. RESULTS: Mean age at presentation to clinic was 15+/-3.5 years, and age of menarche was 12.5+/-2 years; age at menarche did not significantly differ between groups. The most frequent complaints were irregular bleeding (n=10) and mood/behavioral changes (n=6). Girls with autism were significantly (chi(2)=8.89, P=.012) more likely to present with behavioral issues than the other 2 groups. Initial management for the behavior issues in the autism group included nonsteroidal anti-inflammatory drugs (NSAID), oral contraceptives, and education. CONCLUSION: The most common gynecologic complaints of adolescent girls with DS, autism, and CP centered on menstruation and mood disorders. Patients with autism were more likely to present with behavioral issues related to the onset of periods.
10. Callahan K, Shukla-Mehta S, Magee S, Wie M. {{ABA Versus TEACCH: The Case for Defining and Validating Comprehensive Treatment Models in Autism}}. {J Autism Dev Disord};2009 (Aug 1)
The authors analyzed the results of a social validation survey to determine if autism service providers including special education teachers, parents, and administrators demonstrate a preference for the intervention components of Applied Behavior Analysis or Training and Education of Autistic and other Communication Handicapped Children. They also investigated the comprehensiveness of these treatment models for use in public school programs. The findings indicate no clear preference for either model, but a significantly higher level of social validity for components inherent in both approaches. The authors discuss the need for research to define what is meant by comprehensive programming in autism.
11. Chapleau CA, Calfa GD, Lane MC, Albertson AJ, Larimore JL, Kudo S, Armstrong DL, Percy AK, Pozzo-Miller L. {{Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations}}. {Neurobiol Dis};2009 (Aug);35(2):219-233.
Rett syndrome (RTT) is an X chromosome-linked neurodevelopmental disorder associated with the characteristic neuropathology of dendritic spines common in diseases presenting with mental retardation (MR). Here, we present the first quantitative analyses of dendritic spine density in postmortem brain tissue from female RTT individuals, which revealed that hippocampal CA1 pyramidal neurons have lower spine density than age-matched non-MR female control individuals. The majority of RTT individuals carry mutations in MECP2, the gene coding for a methylated DNA-binding transcriptional regulator. While altered synaptic transmission and plasticity has been demonstrated in Mecp2-deficient mouse models of RTT, observations regarding dendritic spine density and morphology have produced varied results. We investigated the consequences of MeCP2 dysfunction on dendritic spine structure by overexpressing ( approximately twofold) MeCP2-GFP constructs encoding either the wildtype (WT) protein, or missense mutations commonly found in RTT individuals. Pyramidal neurons within hippocampal slice cultures transfected with either WT or mutant MECP2 (either R106W or T158M) showed a significant reduction in total spine density after 48 h of expression. Interestingly, spine density in neurons expressing WT MECP2 for 96 h was comparable to that in control neurons, while neurons expressing mutant MECP2 continued to have lower spine density than controls after 96 h of expression. Knockdown of endogenous Mecp2 with a specific small hairpin interference RNA (shRNA) also reduced dendritic spine density, but only after 96 h of expression. On the other hand, the consequences of manipulating MeCP2 levels for dendritic complexity in CA3 pyramidal neurons were only minor. Together, these results demonstrate reduced dendritic spine density in hippocampal pyramidal neurons from RTT patients, a distinct dendritic phenotype also found in neurons expressing RTT-associated MECP2 mutations or after shRNA-mediated endogenous Mecp2 knockdown, suggesting that this phenotype represent a cell-autonomous consequence of MeCP2 dysfunction.
12. Cho SC, Yim SH, Yoo HK, Kim MY, Jung GY, Shin GW, Kim BN, Hwang JW, Kang JJ, Kim TM, Chung YJ. {{Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridization}}. {Psychiatr Genet};2009 (Aug);19(4):177-185.
OBJECTIVES: Autism spectrum disorder (ASD) has been thought to have strong genetic background, but major contributing genes or associated molecular-genetic pathways are yet to be identified. To explore the idiopathic ASD-associated copy number variations (CNVs), we conducted case-control study using whole-genome copy number analysis. METHODS: Whole-genome microarray-based comparative genomic hybridization was carried out on 28 children (24 boys and four girls) diagnosed as ASD and 62 Korean adults (45 males and 17 females) without any signs of abnormalities and family history of genetic disorders as normal controls. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism were used for quantitative verification of the ASD-associated CNVs. RESULTS: Thirty-eight CNVs were identified. Among them, the distributions of copy number loss CNVs on 8p23.1 (odds ratio: 5.1, 95% confidence interval: 1.7-14.5, P=0.003) and on 17p11.2 (odds ratio: uncalculable because of zero cell, P=0.008) were found to be significantly different between ASD and control groups. DEFENSIN family occurs in a cluster at 8p23.1 region. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism coherently showed reduced copy number of DEFENSIN in cases with 8p23.1 copy number loss CNV, which validated microarray-based comparative genomic hybridization results; but there are no known coding genes in the CNV on 17p11.2. CONCLUSION: Our approach as well as results can help to elucidate the genetic mechanism of idiopathic ASD.
13. Coben R, Myers TE. {{The Relative Efficacy of Connectivity Guided and Symptom Based EEG Biofeedback for Autistic Disorders}}. {Appl Psychophysiol Biofeedback};2009 (Aug 1)
Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5-23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.
14. Di Martino A, Shehzad Z, Kelly C, Roy AK, Gee DG, Uddin LQ, Gotimer K, Klein DF, Castellanos FX, Milham MP. {{Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults}}. {Am J Psychiatry};2009 (Aug);166(8):891-899.
OBJECTIVE: The Social Responsiveness Scale-Adult Version (SRS-A) measures autistic traits that are continuously distributed in the general population. Based on increased recognition of the dimensional nature of autistic traits, the authors examined the neural correlates of these traits in neurotypical individuals using the SRS-A and established a novel approach to assessing the neural basis of autistic characteristics, attempting to directly relate SRS-A scores to patterns of functional connectivity observed in the pregenual anterior cingulate cortex, a region commonly implicated in social cognition. METHOD: Resting state functional magnetic resonance imaging scans were collected for 25 neurotypical adults. All participants provided SRS-A ratings completed by an informant who had observed them in natural social settings. Whole brain-corrected connectivity analyses were then conducted using SRS-A scores as a covariate of interest. RESULTS: Across participants, a significant negative relationship between SRS-A scores and the functional connectivity of the pregenual anterior cingulate cortex with the anterior portion of the mid-insula was found. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive connectivity with the pregenual anterior cingulate cortex. In contrast, elevated levels of autistic traits were associated with negative connectivity between these two regions. CONCLUSIONS: Resting state functional connectivity of the pregenual anterior cingulate cortex-insula social network was related to autistic traits in neurotypical adults. Application of this approach in samples with autism spectrum disorders is needed to confirm whether this circuit is dimensionally related to the severity of autistic traits in clinical populations.
15. Dose M. {{Asperger Syndrome}}. {Fortschr Neurol Psychiatr};2009 (Jul 30)Das Asperger-Syndrom.
16. Downs J, Bergman A, Carter P, Anderson A, Palmer GM, Roye D, van Bosse H, Bebbington A, Larsson EL, Smith BG, Baikie G, Fyfe S, Leonard H. {{Guidelines for management of scoliosis in Rett syndrome patients based on expert consensus and clinical evidence}}. {Spine} (Phila Pa 1976);2009 (Aug 1);34(17):E607-617.
STUDY DESIGN: Modified Delphi technique. OBJECTIVE: To develop guidelines for the clinical management of scoliosis in Rett syndrome through evidence review and consensus expert panel opinion. SUMMARY OF BACKGROUND DATA: Rett syndrome is a rare disorder and clinical expertise is thus with small case series. Scoliosis is a frequent association and the evidence base dealing with scoliosis management in this syndrome is limited. Parents of affected girls and women have expressed needs for more information about scoliosis and Rett syndrome. METHODS: An initial draft of scoliosis guidelines was created based on literature review and open-ended questions where the literature was lacking. Perspectives of four parents of Rett syndrome patients informed this initial draft. Access to an online and a Microsoft Word formatted version of the draft were then sent to an international, multidisciplinary panel of clinicians via e-mail with input sought using a 2-stage modified Delphi process to reach consensus agreement. Items included clinical monitoring and intervention before the diagnosis of scoliosis; monitoring after the diagnosis of scoliosis; imaging; therapy and conservative management; bracing; and preoperative, surgical, and postoperative considerations. RESULTS: The first draft contained 71 statements, 65 questions. The second draft comprised 88 items with agreement to strong agreement achieved on 85, to form the final guideline document. A comprehensive, life-span approach to the management of scoliosis in Rett syndrome is recommended that takes into account factors such as physical activity, posture, nutritional and bone health needs. Surgery should be considered when the Cobb angle is approximately 40 degrees to 50 degrees and must be supported by specialist management of anesthesia, pain control, seizures, and early mobilization. CONCLUSION: Evidence- and consensus-based guidelines were successfully created and have the potential to improve care of a complex comorbidity in a rare condition and stimulate research to improve the current limited evidence base.
17. Dubischar-Krivec AM, Neumann N, Poustka F, Braun C, Birbaumer N, Bolte S. {{Calendar calculating in savants with autism and healthy calendar calculators}}. {Psychol Med};2009 (Aug);39(8):1355-1363.
BACKGROUND: Calendar calculation is the ability to quickly name the day that a given date falls on. Previous research has suggested that savant calendar calculation is based on rote memory and the use of rule-based arithmetic skills. The objective of this study was to identify the cognitive processes that distinguish calendar calculation in savant individuals from healthy calendar calculators. METHOD: Savant calendar calculators with autism (ACC, n=3), healthy calendar calculators (HCC, n=3), non-savant subjects with autism (n=6) and healthy calendar calculator laymen (n=18) were included in the study. All participants calculated dates of the present (current month). In addition, ACC and HCC also calculated dates of the past and future 50 years. RESULTS: ACC showed shorter reaction times and fewer errors than HCC and non-savant subjects with autism, and significantly fewer errors than healthy calendar calculator laymen when calculating dates of the present. Moreover, ACC performed faster and more accurate than HCC regarding past dates. However, no differences between ACC and HCC were detected for future date calculation. CONCLUSIONS: The findings may imply distinct calendar calculation strategies in ACC and HCC, with HCC relying on calendar regularities for all types of dates and an involvement of (rote) memory in ACC when processing dates of the past and the present.
18. Dworzynski K, Happe F, Bolton P, Ronald A. {{Relationship between symptom domains in autism spectrum disorders: a population based twin study}}. {J Autism Dev Disord};2009 (Aug);39(8):1197-1210.
Factor structure and relationship between core features of autism (social impairments, communication difficulties, and restricted, repetitive behaviours or interests (RRBIs)) were explored in 189 children from the Twins Early Development Study, diagnosed with autistic spectrum disorders (ASDs) using the Development and Wellbeing Assessment (DAWBA; Goodman et al. in J Child Psychol Psyc 41:645-655, 2000). A bottom-up approach (analysis 1) used principal component factor analysis of DAWBA items indicating five factors, the first three mapping on the triad. In analysis 2, applying top-down DSM-IV criteria, correlations between domains were modest, strongest between social and communication difficulties. Cross-twin cross-trait correlations suggested small shared genetic effects between RRBIs and other symptoms. These findings from a clinical sample of twins indicate a fractionation of social/communicative and RRBI symptoms in ASD.
19. Gaigg SB, Bowler DM. {{Brief report: Attenuated emotional suppression of the attentional blink in Autism Spectrum Disorder: another non-social abnormality?}} {J Autism Dev Disord};2009 (Aug);39(8):1211-1217.
Twenty-five individuals with Autism Spectrum Disorder and 25 typically developed individuals participated in an Attentional Blink paradigm to determine whether emotional words would capture attention similarly in the two groups. Whilst the emotionality of words facilitated attention in typical comparison participants, this effect was attenuated in the ASD group. The magnitude of the emotional modulation of attention in ASD also correlated significantly with participants’ VIQ, which was not observed for the comparison group. Together these observations replicate and extend the findings of Corden et al. (J Autism Develop Disord 38:1072-1080, 2008) and implicate abnormalities in emotional processes outside the broader context of social cognition in ASD. We discuss our findings in relation to possible abnormalities in amygdala function that may underlie the disorder.
20. Gamliel I, Yirmiya N, Jaffe DH, Manor O, Sigman M. {{Developmental trajectories in siblings of children with autism: cognition and language from 4 months to 7 years}}. {J Autism Dev Disord};2009 (Aug);39(8):1131-1144.
We compared the cognitive and language development at 4, 14, 24, 36, 54 months, and 7 years of siblings of children with autism (SIBS-A) to that of siblings of children with typical development (SIBS-TD) using growth curve analyses. At 7 years, 40% of the SIBS-A, compared to 16% of SIBS-TD, were identified with cognitive, language and/or academic difficulties, identified using direct tests and/or parental reports. This sub-group was identified as SIBS-A-broad phenotype (BP). Results indicated that early language scores (14-54 months), but not cognitive scores of SIBS-A-BP and SIBS-A-nonBP were significantly lower compared to the language scores of SIBS-TD, and that the rate of development was also significantly different, thus pinpointing language as a major area of difficulty for SIBS-A during the preschool years.
21. Gilger MA, Redel CA. {Autism and the gut}. {Pediatrics};2009 (Aug);124(2):796-798.
22. Goodlin-Jones B, Schwichtenberg AJ, Iosif AM, Tang K, Liu J, Anders TF. {{Six-month persistence of sleep problems in young children with autism, developmental delay, and typical development}}. {J Am Acad Child Adolesc Psychiatry};2009 (Aug);48(8):847-854.
OBJECTIVE: This study examined the persistence of sleep problems in preschool children with autism and two matched comparison groups: children with developmental delay without autism and typically developing children. Sleep problems were defined subjectively by parent report, by the Children’s Sleep Habits Questionnaire (CSHQ), and objectively by quantitative Research Diagnostic Criteria (RDC) derived from actigraphic recordings. METHOD: Children were studied on three occasions, each separated by a 3-month interval. At each assessment, the children were recorded actigraphically for 1 week, and parents completed sleep-wake diaries and the CSHQ. Descriptive statistics and odds ratios were used to assess the occurrence and stability of sleep problems within children and across groups and to explore how actigraph- and CSHQ-defined sleep problems affect parental sleep problem reports. RESULTS: Parent reports of a generic sleep problem were more prevalent than RDC- and CSHQ-defined sleep problems, especially for children with neurodevelopmental disorders. For all groups, objectively measured sleep problems were rarely persistent during the 6-month period. The children in both neurodevelopmental groups, however, had more sleep problems on one or two occasions, using actigraph and the CSHQ, than typically developing children. CONCLUSIONS: Objective and subjective measures of sleep problems in preschool-aged children produce different results. In a community sample, the rate of actigraph- and CSHQ-defined sleep problems in children with autism did not differ from rates for typically developing children, although the parent report of a generic sleep problem was significantly greater.
23. Hamilton AF. {{Goals, intentions and mental states: challenges for theories of autism}}. {J Child Psychol Psychiatry};2009 (Aug);50(8):881-892.
The ability to understand the goals and intentions behind other people’s actions is central to many social interactions. Given the profound social difficulties seen in autism, we might expect goal understanding to be impaired in these individuals. Two influential theories, the ‘broken mirror’ theory and the mentalising theory, can both predict this result. However, a review of the current data provides little empirical support for goal understanding difficulties; several studies demonstrate normal performance by autistic children on tasks requiring the understanding of goals or intentions. I suggest that this conclusion forces us to reject the basic broken mirror theory and to re-evaluate the breadth of the mentalising theory. More subtle theories which distinguish between different types of mirroring and different types of mentalising may be able to account for the present data, and further research is required to test and refine these theories.
24. Haswell CC, Izawa J, L RD, S HM, Shadmehr R. {{Representation of internal models of action in the autistic brain}}. {Nat Neurosci};2009 (Aug);12(8):970-972.
Children with autism spectrum disorder (ASD) have deficits in motor control, imitation and social function. Does a dysfunction in the neural basis of representing internal models of action contribute to these problems? We measured patterns of generalization as children learned to control a novel tool and found that the autistic brain built a stronger than normal association between self-generated motor commands and proprioceptive feedback; furthermore, the greater the reliance on proprioception, the greater the child’s impairments in social function and imitation.
25. Honda H, Shimizu Y, Nitto Y, Imai M, Ozawa T, Iwasa M, Shiga K, Hira T. {{Extraction and Refinement Strategy for detection of autism in 18-month-olds: a guarantee of higher sensitivity and specificity in the process of mass screening}}. {J Child Psychol Psychiatry};2009 (Aug);50(8):972-981.
BACKGROUND: For early detection of autism, it is difficult to maintain an efficient level of sensitivity and specificity based on observational data from a single screening. The Extraction and Refinement (E&R) Strategy utilizes a public children’s health surveillance program to produce maximum efficacy in early detection of autism. In the extraction stage, all cases at risk of childhood problems, including developmental abnormality, are identified; in the refinement stage, cases without problems are excluded, leaving only cases with conclusive diagnoses. METHODS: The city of Yokohama, Japan, conducts a routine child health surveillance program for children at 18 months in which specialized public health nurses administer YACHT-18 (Young Autism and other developmental disorders CHeckup Tool), a screening instrument to identify children at risk for developmental disorders. Children who screen positive undergo further observation, and those without disorders are subsequently excluded. To study the efficacy of early detection procedures for developmental disorders, including autism, 2,814 children born in 1988, examined at 18 months of age, and not already receiving treatment for diseases or disorders were selected. RESULTS: In the extraction stage, 402 (14.3%) children were identified for follow-up. In the refinement stage, 19 (.7%) of these were referred to the Yokohama Rehabilitation Center and diagnosed with developmental disorders. The extraction stage produced four false negatives, bringing total diagnoses of developmental disorders to 23 (.8%) – including 5 with autistic disorder and 9 with pervasive developmental disorder – not otherwise specified (PDDNOS). Sensitivity was 60% for autistic disorder and 82.6% for developmental disorders. Specificity for developmental disorders rose to 100% with the E&R Strategy. Picture cards used in YACHT-18 provided a finer screen that excluded some false positive cases. CONCLUSIONS: An extraction and refinement methodology utilizing child health surveillance programs achieve high efficacy for early detection of autism.
26. Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ. {{Incidence of gastrointestinal symptoms in children with autism: a population-based study}}. {Pediatrics};2009 (Aug);124(2):680-686.
OBJECTIVE: To determine whether children with autism have an increased incidence of gastrointestinal symptoms compared with matched control subjects in a population-based sample. DESIGN/METHODS: In a previous study including all of the residents of Olmsted County, Minnesota, aged <21 years between 1976 and 1997, we identified 124 children who fulfilled criteria on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for a research diagnosis of autism. Two matched control subjects were identified for each case subject. Through the Rochester Epidemiology Project, all medical diagnoses, are indexed for computerized retrieval. Gastrointestinal diagnoses before 21 years of age were grouped into 5 categories: (1) constipation; (2) diarrhea; (3) abdominal bloating, discomfort, or irritability; (4) gastroesophageal reflux or vomiting; and (5) feeding issues or food selectivity. The cumulative incidence of each category was calculated by using the Kaplan-Meier method. Cox proportional hazards models were fit to estimate the risk ratios (case subjects versus control subjects) and corresponding 95% confidence intervals. RESULTS: Subjects were followed to median ages of 18.2 (case subjects) and 18.7 (control subjects) years. Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category. CONCLUSIONS: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.
27. James SJ, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW. {{Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism}}. {Faseb J};2009 (Aug);23(8):2374-2383.
Research into the metabolic phenotype of autism has been relatively unexplored despite the fact that metabolic abnormalities have been implicated in the pathophysiology of several other neurobehavioral disorders. Plasma biomarkers of oxidative stress have been reported in autistic children; however, intracellular redox status has not yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG) in cell extracts and isolated mitochondria as a measure of intracellular redox capacity. The results indicated that the GSH/GSSG redox ratio was decreased and percentage oxidized glutathione increased in both cytosol and mitochondria in the autism LCLs. Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.
28. Jou RJ, Minshew NJ, Melhem NM, Keshavan MS, Hardan AY. {{Brainstem volumetric alterations in children with autism}}. {Psychol Med};2009 (Aug);39(8):1347-1354.
BACKGROUND: Although several studies have examined brainstem volume in autism, results have been mixed and no investigation has specifically measured gray- and white-matter structures. The aim of this investigation was to assess gray- and white-matter volumes in children with autism. METHOD: Subjects included 22 right-handed, non-mentally retarded boys with autism and 22 gender- and age-matched controls. Magnetic resonance imaging (MRI) scans were obtained using a 1.5-T scanner and volumetric measurements were performed using the BRAINS2 software package. Gray- and white-matter volumes were measured using a semi-automated segmentation process. RESULTS: There were no significant differences in age and total brain volume (TBV) between the two groups but full-scale IQ was higher in controls. A decrease in brainstem gray-matter volume was observed in the autism group before and after controlling for TBV. No significant differences were observed in white-matter volume. A significant relationship was observed between brainstem gray-matter volume and oral sensory sensitivity as measured by the Sensory Profile Questionnaire (SPQ). CONCLUSIONS: Findings from this study are suggestive of brainstem abnormalities in autism involving gray-matter structures with evidence supporting the existence of a relationship between these alterations and sensory deficits. These results are consistent with previous investigations and support the existence of disturbances in brainstem circuitry thought to be implicated in the sensory dysfunction observed in autism.
29. Kennedy DP. {{Neural correlates of autistic traits in the general population: insights into autism}}. {Am J Psychiatry};2009 (Aug);166(8):849-851.
30. Kilpinen H, Ylisaukko-oja T, Rehnstrom K, Gaal E, Turunen JA, Kempas E, von Wendt L, Varilo T, Peltonen L. {{Linkage and linkage disequilibrium scan for autism loci in an extended pedigree from Finland}}. {Hum Mol Genet};2009 (Aug 1);18(15):2912-2921.
Population isolates, such as Finland, have proved beneficial in mapping rare causative genetic variants due to a limited number of founders resulting in reduced genetic heterogeneity and extensive linkage disequilibrium (LD). We have here used this special opportunity to identify rare alleles in autism by genealogically tracing 20 autism families into one extended pedigree with verified genealogical links reaching back to the 17th century. In this unique pedigree, we performed a dense microsatellite marker genome-wide scan of linkage and LD and followed initial findings with extensive fine-mapping. We identified a putative autism susceptibility locus at 19p13.3 and obtained further evidence for previously identified loci at 1q23 and 15q11-q13. Most promising candidate genes were TLE2 and TLE6 clustered at 19p13 and ATP1A2 at 1q23.
31. Klein-Tasman BP, Phillips KD, Lord C, Mervis CB, Gallo FJ. {{Overlap with the autism spectrum in young children with Williams syndrome}}. {J Dev Behav Pediatr};2009 (Aug);30(4):289-299.
OBJECTIVE: The sociocommunicative abnormalities of young children with Williams syndrome (WS) with limited language were compared with those of children with clinical diagnoses of autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), or nonspectrum developmental disability. METHOD: Participants were 30 children with WS and individually matched groups of participants with autism (n = 28), PDD-NOS (n = 17), and mixed etiology nonspectrum developmental disabilities (n = 16). The autism, PDD-NOS, and mixed etiology groups were matched individually to the children with WS for age, sex, and developmental level. All participants were administered the Autism Diagnostic Observation Schedule Module 1 and the Mullen Scales of Early Learning. RESULTS: As a group, children with WS with limited language showed fewer sociocommunicative abnormalities than children with autism, about the same level as children with PDD-NOS, and more abnormalities in reciprocity social interaction than participants in the mixed etiology group. Examination of the subgroup of participants with WS matched and compared with children with PDD-NOS indicated that half of the children showed fewer abnormalities than their individual matches with PDD-NOS, whereas half of the children with WS showed more abnormalities than their matches with PDD-NOS. CONCLUSION: Sociocommunicative difficulties are present for many children with WS and overlap with the autism spectrum. The results of this investigation suggest that these abnormalities are not accounted for by developmental delay alone, and care should be taken to avoid diagnostic overshadowing in young children with WS.
32. Koenig K, De Los Reyes A, Cicchetti D, Scahill L, Klin A. {{Group intervention to promote social skills in school-age children with pervasive developmental disorders: reconsidering efficacy}}. {J Autism Dev Disord};2009 (Aug);39(8):1163-1172.
A consistent result in the evaluation of group-delivered intervention to promote social reciprocity in children with PDDs is that outcome data are inconclusive. Lack of robust evidence of efficacy confounds understanding of these interventions and their value to the field. It is conceivable that the construct of impaired social reciprocity in PDD presents unique circumstances that require special consideration when evaluating the evidence base. Social reciprocity and impairment in social functioning are complex constructs, which require a multi-dimensional, multi-method approach to intervention and measurement of gains. The existing paradigm for evaluating the evidence base of intervention may need modification to permit a more intricate analysis of the extant research, and increase the sophistication of future research.
33. Koyama T, Tachimori H, Sawamura K, Koyama A, Naganuma Y, Makino H, Takeshima T. {{Mental health literacy of autism spectrum disorders in the Japanese general population}}. {Soc Psychiatry Psychiatr Epidemiol};2009 (Aug);44(8):651-657.
OBJECTIVE: We aimed to clarify the public’s mental health literacy of autism spectrum disorders (ASD). METHODS: Using a vignette of a young child, 500 Japanese participants were asked their perspectives, such as causes and appropriate coping strategies. For each response from those respondents who correctly identified the child as having autism, we tested the effects of sex and generation. RESULTS: Two hundred twenty-nine respondents (45.8%) correctly identified the child as having autism. Significantly (P < 0.05) more females planned practical coping strategies such as contacting public agencies, whereas males had relatively more irrelevant perceptions, for example, significantly more males attributed ASD to social environment. Significantly more young respondents expected psychiatric treatments such as antipsychotic administration to be effective, and more seniors estimated low that the prevalence is approximately 0.01% or less. CONCLUSIONS: The mental health literacy of ASD among the Japanese public appears to be acceptable but there is still much room for improvement. Females showed more accurate knowledge, possibly reflecting gender roles. Some young people are not likely to know of the impact of psychiatric treatment, and seniors appear to be unaware of the current broadened recognition of ASD. Continued efforts to disseminate accurate information are required, particularly among males.
34. Lane AE, Young RL, Baker AE, Angley MT. {{Sensory Processing Subtypes in Autism: Association with Adaptive Behavior}}. {J Autism Dev Disord};2009 (Jul 31)
Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes were differentiated by taste and smell sensitivity and movement-related sensory behavior. Further, sensory processing subtypes predicted communication competence and maladaptive behavior. The findings of this study lay the foundation for the generation of more specific hypotheses regarding the mechanisms of sensory processing dysfunction in autism, and support the continued use of sensory-based interventions in the remediation of communication and behavioral difficulties in autism.
35. Langstrom N, Grann M, Ruchkin V, Sjostedt G, Fazel S. {{Risk factors for violent offending in autism spectrum disorder: a national study of hospitalized individuals}}. {J Interpers Violence};2009 (Aug);24(8):1358-1370.
Little is known about risk factors for violence among individuals with autism spectrum disorder (ASD). This study uses data from Swedish longitudinal registers for all 422 individuals hospitalized with autistic disorder or Asperger syndrome during 1988-2000 and compares those committing violent or sexual offenses with those who did not. Thirty-one individuals with ASD (7%) were convicted of violent nonsexual crimes and two of sexual offenses. Violent individuals with ASD are more often male and diagnosed with Asperger syndrome rather than autistic disorder. Furthermore, comorbid psychotic and substance use disorders are associated with violent offending. We conclude that violent offending in ASD is related to similar co-occurring psychopathology as previously found among violent individuals without ASD. Although this study does not answer whether ASDs are associated with increased risk of violent offending compared with the general population, careful risk assessment and management may be indicated for some individuals with Asperger syndrome.
36. Lee PS, Yerys BE, Della Rosa A, Foss-Feig J, Barnes KA, James JD, VanMeter J, Vaidya CJ, Gaillard WD, Kenworthy LE. {{Functional connectivity of the inferior frontal cortex changes with age in children with autism spectrum disorders: a fcMRI study of response inhibition}}. {Cereb Cortex};2009 (Aug);19(8):1787-1794.
Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.
37. Lidstone JS, Fernyhough C, Meins E, {{Whitehouse AJ. Brief report: Inner speech impairment in children with autism is associated with greater nonverbal than verbal skills}}. {J Autism Dev Disord};2009 (Aug);39(8):1222-1225.
We present a new analysis of Whitehouse, Maybery, and Durkin’s (2006, Experiment 3) data on inner speech in children with autism (CWA). Because inner speech development is thought to depend on linguistically mediated social interaction, we hypothesized that children with both autism and a nonverbal > verbal (NV > V) skills profile would show the greatest inner speech impairment. CWA and typically developing controls (n = 23 in each group) undertook a timed mathematical task-switching test, known to benefit from inner speech use. Participants completed the task with and without articulatory suppression (AS), which disrupts inner speech. The hypothesis was supported: AS interference varied with cognitive profile among CWA but not among controls. Only the NV > V autism group showed no AS interference, indicating an inner speech impairment.
38. Lubisch N, Roskos R, Berkenbosch JW. {{Dexmedetomidine for procedural sedation in children with autism and other behavior disorders}}. {Pediatr Neurol};2009 (Aug);41(2):88-94.
Dexmedetomidine has been increasingly in use for pediatric noninvasive procedural sedation. This retrospective study examined experience in children with autism and other neurobehavioral disorders, populations often difficult to sedate. Records of children with autism or neurobehavioral disorders sedated with dexmedetomidine at Chris Evert Children’s Hospital and Kosair Children’s Hospital were reviewed. Demographic and sedation-related data were collected, including sedative doses, time to sedation, efficacy, and complications. Comparisons of sedative doses, efficacy between autism and neurobehavioral patients, and analysis of age-related factors were performed. In all, 315 patients were sedated, most commonly for magnetic resonance imaging. Mean induction and total dexmedetomidine doses were 1.4 +/- 0.6 and 2.6 +/- 1.6 microg/kg, respectively, with no differences between autism and neurobehavior patients. Most patients (90%) patients received concomitant midazolam. There was an age-related decrease in dexmedetomidine dose, independent of midazolam use. Seven patients required intervention for hypotension, bradycardia, or both, and only one adverse respiratory event (obstruction requiring nasopharyngeal airway placement) occurred. There were two episodes of overt recovery-related agitation. All but four procedures were successfully completed (4/315, or 98.7%). Dexmedetomidine with or without midazolam was an effective sedative in this population. The regimen appeared to be well tolerated with few adverse events, including recovery-related agitation, and appears to be an attractive option for this population.
39. Mattila ML, Jussila K, Kuusikko S, Kielinen M, Linna SL, Ebeling H, Bloigu R, Joskitt L, Pauls D, Moilanen I. {{When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism spectrum disorders in primary school-aged children?}} {Eur Child Adolesc Psychiatry};2009 (Aug);18(8):499-509.
The aims of this study were, firstly, to study the association between parents’ and teachers’ ratings for the Finnish version of the Autism Spectrum Screening Questionnaire (ASSQ), secondly, to find out whether the original cut-off scores of the ASSQ identify primary school-aged children with Asperger syndrome (AS) or autism by using the Finnish ASSQ, and thirdly, to evaluate the validity of the ASSQ. Parents and/or teachers of higher-functioning (full-scale intelligence quotient > or = 50) 8-year-old total population school children (n = 4,408) and 7-12-year-old outpatients with AS/autism (n = 47) completed the Finnish version of the ASSQ. Agreement between informants was slight. In the whole total population, low positive correlation was found between parents’ and teachers’ ratings, while in the sample of high-scoring children the correlation turned out to be negative. A cut-off of 30 for parents’ and teacher’s summed score and 22 for teachers’ single score is recommended. A valid cut-off for parents’ single score could not been estimated. The clinicians are reminded that the ASSQ is a screening instrument, not a diagnosing instrument. The importance of using both parents’ and teachers’ ratings for screening in clinical settings is underlined.
40. Milshtein S, Yirmiya N, Oppenheim D, Koren-Karie N, Levi S. {{Resolution of the Diagnosis Among Parents of Children with Autism Spectrum Disorder: Associations with Child and Parent Characteristics}}. {J Autism Dev Disord};2009 (Jul 31)
Resolution with the diagnosis of one’s child involves coming to terms with and accepting the diagnosis and its implications. Parental resolution with the diagnosis was examined among 61 mothers and 60 fathers of 61 children with autism spectrum disorders aged 2-17 years. We investigated resolution rates and subtypes, and associations between resolution status and child characteristics (CA, gender, MA, adaptive behavior, diagnosis type, time elapsed since diagnosis) and parent characteristics (age, gender, IQ, broad autism phenotype index, special needs’ impact on family). Nearly half of the parents were classified as resolved. Maternal but not paternal resolution status was associated with reported negative impact of raising a child with a disability on family life, but not with other characteristics of the child or the parent.
41. Mitchell SR, Reiss AL, Tatusko DH, Ikuta I, Kazmerski DB, Botti JA, Burnette CP, Kates WR. {{Neuroanatomic alterations and social and communication deficits in monozygotic twins discordant for autism disorder}}. {Am J Psychiatry};2009 (Aug);166(8):917-925.
OBJECTIVE: Investigating neuroanatomic differences in monozygotic twins who are discordant for autism can help unravel the relative contributions of genetics and environment to this pervasive developmental disorder. The authors used magnetic resonance imaging (MRI) to investigate several brain regions of interest in monozygotic twins who varied in degree of phenotypic discordance for narrowly defined autism. METHOD: The subjects were 14 pairs of monozygotic twins between the ages of 5 and 14 years old and 14 singleton age- and gender-matched typically developing comparison subjects. The monozygotic twin group was a cohort of children with narrowly defined autistic deficits and their co-twins who presented with varying levels of autistic deficits. High-resolution MRIs were acquired and volumetric/area measurements obtained for the frontal lobe, amygdala, and hippocampus and subregions of the prefrontal cortex, corpus callosum, and cerebellar vermis. RESULTS: No neurovolumetric/area differences were found between twin pairs. Relative to typically developing comparison subjects, dorsolateral prefrontal cortex volumes and anterior areas of the corpus callosum were significantly altered in autistic twins, and volumes of the posterior vermis were altered in both autistic twins and co-twins. Intraclass correlation analysis of brain volumes between children with autism and their co-twins indicated that the degree of within-pair neuroanatomic concordance varied with brain region. In the group of subjects with narrowly defined autism only, dorsolateral prefrontal cortex, amygdala, and posterior vermis volumes were significantly associated with the severity of autism based on scores from the Autism Diagnostic Observation Schedule-Generic. CONCLUSIONS: These findings support previous research demonstrating alterations in the prefrontal cortex, corpus callosum, and posterior vermis in children with autism and further suggest that alterations are associated with the severity of the autism phenotype. Continued research involving twins who are concordant and discordant for autism is essential to disentangle the genetic and environmental contributions to autism.
42. Mohammad NS, Jain JM, Chintakindi KP, Singh RP, Naik U, Akella RR. {{Aberrations in folate metabolic pathway and altered susceptibility to autism}}. {Psychiatr Genet};2009 (Aug);19(4):171-176.
OBJECTIVE: To investigate whether genetic polymorphisms are the underlying causes for aberrations in folate pathway that was reported in autistic children. BASIC METHODS: A total of 138 children diagnosed as autistic based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria and Autism Behavior Checklist scoring and 138 age and sex matched children who are nonautistic were tested for five genetic polymorphisms, that is, cytosolic serine hydroxyl methyl transferase (SHMT1 C1420T), methylene tetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), methionine synthase reductase (MTRR A66G), methionine synthase (MS A2756G) using PCR-restriction fragment length polymorphism methods. Fisher’s exact test and logistic regression analysis were used for statistical analyses. RESULTS: MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (16.3 vs. 6.5%) with 2.79-fold increased risk for autism [95% confidence interval (CI): 1.58-4.93]. The frequencies of MTRR 66A allele (12.7 vs. 21.0%) and SHMT 1420T allele (27.9 vs. 45.3%) were lower in autistic group compared with nonautistic group with odds ratios 0.55 (95% CI: 0.35-0.86) and 0.44 (95% CI: 0.31-0.62), respectively, indicating reduced risk. MTHFR 1298C-allele frequency was similar in both the groups (53.3 vs. 53.6%) and hence individually not associated with any risk. However, this allele was found to act additively in the presence of MTHFR 677T allele as evidenced by 8.11-fold (95% CI: 2.84-22.92) risk associated with MTHFR 677CT+TT/1298AC+CC genotypes cumulatively. CONCLUSION: MTHFR C677T is a risk factor, whereas MTRR A66G and SHMT C1420T polymorphisms reduce risk for autism. MTHFR A1298C acts additively in increasing the risk for autism.
43. Moore TR, Symons FJ. {{Adherence to behavioral and medical treatment recommendations by parents of children with autism spectrum disorders}}. {J Autism Dev Disord};2009 (Aug);39(8):1173-1184.
The extent to which parents of children with intellectual or developmental disabilities are adherent to prescribed treatments has not been investigated. In this treatment adherence study, parents (n = 220) of children with autism spectrum disorders were surveyed regarding implementation of recommended treatments to manage problem behavior of their children living at home. Overall adherence to medical treatment recommendations was significantly greater than adherence to behavioral treatment recommendations (p < .002). Of the behavioral treatment recommendations, parents reported greater adherence to reinforcement (81.7%) than punishment (68.9%). Child diagnosis (p < .002) and the diagnosis x marital status interaction (p < .05) were significantly associated with reported adherence to behavioral and medical treatment, respectively. Results are discussed in light of the need to address adherence enhancement and measurement methods.
44. Motil KJ, Morrissey M, Caeg E, Barrish JO, Glaze DG. {{Gastrostomy placement improves height and weight gain in girls with Rett syndrome}}. {J Pediatr Gastroenterol Nutr};2009 (Aug);49(2):237-242.
BACKGROUND: Growth failure and undernutrition complicate the clinical course of girls with Rett syndrome (RTT). These abnormalities are, in part, the consequence of oral motor dysfunction and inadequate dietary intake. OBJECTIVE: To determine whether gastrostomy placement for nutritional therapy alters the natural history of growth failure and undernutrition in RTT. HYPOTHESIS: We hypothesized that gastrostomy placement for nutritional therapy reverses the decline in height, weight, and body mass index (BMI) z scores in RTT. METHODS: Standard stadiometric and anthropometric measures were obtained to derive height, weight, and BMI z scores and estimates of fat-free mass (FFM) and body fat in a cohort of girls (n = 92) with RTT before and after gastrostomy placement. Methyl-CpG-binding protein 2 (MECP2) mutations and the presence or absence of a fundoplication were recorded. RESULTS: The differences in height (n = 73), weight (n = 81), and BMI (n = 81) z score slopes before and after gastrostomy placement were 1.31 + 2.06 (P < 0.001), 2.38 +/- 3.18 (P < 0.001), and 3.25 +/- 3.32 (P < 0.001), respectively. FFM and body fat (n = 43) increased after gastrostomy by 41 +/- 27 g/cm height (P < 0.001) and 7.5% +/- 5.7% body weight (P < 0.001), respectively. The differences in height, weight, and BMI z score slopes were similar regardless of the age at which the gastrostomy was placed. The differences in height, weight, and BMI z score slopes, as well as the change in FFM and body fat dep
