1. Bal E, Harden E, Lamb D, Van Hecke AV, Denver JW, Porges SW. {{Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state}}. {J Autism Dev Disord} (Mar);40(3):358-370.
Respiratory Sinus Arrhythmia (RSA), heart rate, and accuracy and latency of emotion recognition were evaluated in children with autism spectrum disorders (ASD) and typically developing children while viewing videos of faces slowly transitioning from a neutral expression to one of six basic emotions (e.g., anger, disgust, fear, happiness, sadness, and surprise). Children with ASD were slower in emotion recognition and selectively made more errors in detecting anger. ASD children had lower amplitude RSA and faster heart rate. Within the ASD group, children with higher amplitude RSA recognized emotions faster. Less severe ASD symptoms and increased gaze to the eye region in children with ASD were related to more accurate emotion recognition.
2. Belmonte MK, Gomot M, Baron-Cohen S. {{Visual attention in autism families: ‘unaffected’ sibs share atypical frontal activation}}. {J Child Psychol Psychiatry} (Mar 1);51(3):259-276.
Background: In addition to their more clinically evident abnormalities of social cognition, people with autism spectrum conditions (ASC) manifest perturbations of attention and sensory perception which may offer insights into the underlying neural abnormalities. Similar autistic traits in ASC relatives without a diagnosis suggest a continuity between clinically affected and unaffected family members. Methods: We applied fMRI in the context of a non-social task of visual attention in order to determine whether this continuity persists at the level of brain physiology. Results: Both boys with ASC and clinically unaffected brothers of people with ASC were impaired at a visual divided-attention task demanding conjunction of attributes from rapidly and simultaneously presented, spatially disjoint stimuli and suppression of spatially intervening distractors. In addition, both groups in comparison to controls manifested atypical fronto-cerebellar activation as a function of distractor congruence, and the degree of this frontal atypicality correlated with psychometric measures of autistic traits in ASC and sibs. Despite these resemblances between the ASC and sib groups, an exploratory, hypothesis-generating analysis of correlations across brain regions revealed a decrease in overall functional correlation only in the ASC group and not in the sibs. Conclusions: These results establish a neurophysiological correlate of familial susceptibility to ASC, and suggest that whilst abnormal time courses of frontal activation may reflect processes permissive of autistic brain development, abnormal patterns of functional correlation across a wider array of brain regions may relate more closely to autism’s determinants.
3. Brownlow C. {{Presenting the self: negotiating a label of autism}}. {J Intellect Dev Disabil} (Mar);35(1):14-21.
BACKGROUND: An important element in the experiences of people with autism is the key role played by therapeutic interventions. This paper examines the role of therapeutic intervention and the construction of individuals with autism in the therapeutic relationship. METHOD: The contributions to four online asynchronous discussion lists were analysed using discourse analysis over a 3-month period. FINDINGS: Two key themes identified in the data are presented. These comprise issues concerning therapeutic intervention and issues related to the employment opportunities of adults with autism. CONCLUSIONS: In this paper the notion that people with autism must change in order to accommodate the non-autistic world is discussed. The author seeks to present an alternative construction of autism as a difference rather than a deficit or deviance and to examine the negotiation of a place for a person with autism within a neurologically typical dominated society.
4. Carbone PS, Behl DD, Azor V, Murphy NA. {{The medical home for children with autism spectrum disorders: parent and pediatrician perspectives}}. {J Autism Dev Disord} (Mar);40(3):317-324.
This qualitative study examines differences between perceptions of parents and pediatricians regarding the needs of children with autism spectrum disorders (ASDs) and their families within the medical home. Two separate focus groups of parents of children with ASDs and pediatricians were conducted. Parents and pediatricians identify unmet needs within medical homes of children with ASDs. Parents perceived that physicians did not act early upon their concerns about development, and that care is less comprehensive, coordinated and family-centered than desired. Pediatricians desire to improve services but cite lack of time, training and resources as barriers. Medical homes for children with ASDs would benefit from better pediatrician ASD education and medical systems that support extended visits, care coordination and interdisciplinary collaboration.
5. Cederlund M, Hagberg B, Gillberg C. {{Asperger syndrome in adolescent and young adult males. Interview, self – and parent assessment of social, emotional, and cognitive problems}}. {Res Dev Disabil} (March – April);31(2):287-298.
Descriptive and comparative follow-up studies of young adult males with Asperger syndrome (AS) diagnosed in childhood, using both interview, self- and parent assessment instruments for the study of aspects of emotional well-being, social functioning, and cognitive-practical skills have not been performed in the past. One-hundred males with AS diagnosed in childhood were approached for the assessment using the Asperger Syndrome Diagnostic Interview (ASDI), (personal and parent interview), the Leiter-R-Questionnaires, the Beck Depression Inventory (BDI), and the Dysexecutive Questionnaire (DEX). About 75% of the targeted group participated. The ASDI results came out significantly different at personal vs parent interviews in several key domains. In contrast, the Leiter-R-Questionnaires, showed no significant differences across the individuals with AS and their parents in the scoring of cognitive/social and emotional/adaptive skills. The BDI proved to be an adequate screening instrument for depression in that it correctly identified the vast majority of cases with clinical depression in the AS group. The DEX results suggested an executive function deficit problem profile in males with AS as severe as that reported in groups of individuals with traumatic brain injury and schizophrenia. Interviews (personal and collateral), and self-rating and parent-rating questionnaires all have a role in the comprehensive diagnostic process in AS and other autism spectrum disorders, and could be used as adjuncts when evaluating whether or not individuals meeting diagnostic symptom criteria for the condition have sufficient problems in daily life to warrant a clinical diagnosis of AS.
6. Coben R, Linden M, Myers TE. {{Neurofeedback for autistic spectrum disorder: a review of the literature}}. {Appl Psychophysiol Biofeedback} (Mar);35(1):83-105.
There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.
7. Coben R, Myers TE. {{The relative efficacy of connectivity guided and symptom based EEG biofeedback for autistic disorders}}. {Appl Psychophysiol Biofeedback} (Mar);35(1):13-23.
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.
8. Crane L, Goddard L, Pring L. {{Brief Report: self-defining and everyday autobiographical memories in adults with autism spectrum disorders}}. {J Autism Dev Disord} (Mar);40(3):383-391.
Autobiographical memory impairments in autism spectrum disorders (ASD) have been attributed to a failure in using the self as an effective memory organisational system. To explore this hypothesis, we compared self-defining and everyday memories in adults with and without ASD. Results demonstrated that both groups were able to distinguish between self-defining and everyday memories, although the ASD group generated fewer specific memories overall. Despite qualitative similarities between the narratives of the two groups, the adults with ASD extracted less meaning from their narratives. Difficulties in eliciting meaning from memories suggests a failure in using past experiences to update the self. We therefore propose that the self-memory relationship might be static, rather than dynamic, in ASD.
9. David N, Aumann C, Bewernick BH, Santos NS, Lehnhardt FG, Vogeley K. {{Investigation of mentalizing and visuospatial perspective taking for self and other in asperger syndrome}}. {J Autism Dev Disord} (Mar);40(3):290-299.
Mentalizing refers to making inferences about other people’s mental states, whereas visuospatial perspective taking refers to inferring other people’s viewpoints. Both abilities seem vital for social functioning; yet, their exact relationship is unclear. We directly compared mentalizing and visuospatial perspective taking in nineteen adults with Asperger syndrome (AS) and fifteen control participants with the same stimulus material. Stimuli depicted virtual characters surrounded by two different objects. Virtual characters expressed a preference for one of the objects indicated by facial expression, gestures or head/body orientation. Compared to controls, participants with AS showed significantly increased reaction times and decreased accuracy for mentalizing (i.e., when inferring the virtual character’s preference from the character’s nonverbal bodily cues). By contrast, there were no significant group differences in perspective taking (i.e., by mental own-body transformations). These findings demonstrate, first, specific deficits in AS when mental states have to be inferred from nonverbal social cues. Second, visuospatial perspective taking may not necessarily be related to social impairments occurring in autism spectrum disorders.
10. Durkin MS, Maenner MJ, Newschaffer CJ. {{Estimated autism risk, older reproductive age, and parameterization}}. {Am J Public Health} (Mar);100(3):389-390; author reply 390.
11. El-Fishawy P, State MW. {{The genetics of autism: key issues, recent findings, and clinical implications}}. {Psychiatr Clin North Am} (Mar);33(1):83-105.
Autism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding opportunities for the development of novel treatments and understanding of their natural history. Although the underlying genetic architecture of ASDs is not yet known, the literature demonstrates that it is not a monogenic disorder with mendelian inheritance, rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. This article reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of common and rare variant discoveries.
12. Gillberg C, Billstedt E, Sundh V, Gillberg IC. {{Mortality in autism: a prospective longitudinal community-based study}}. {J Autism Dev Disord} (Mar);40(3):352-357.
The purposes of the present study were to establish the mortality rate in a representative group of individuals (n = 120) born in the years 1962-1984, diagnosed with autism/atypical autism in childhood and followed up at young adult age (>or=18 years of age), and examine the risk factors and causes of death. The study group, which constituted a total population sample of children with these diagnoses, were followed up in Swedish registers. Nine (7.5%) of the 120 individuals with autism had died at the time of follow-up, a rate 5.6 times higher than expected. The mortality rate was significantly higher among the females. Associated medical disorders (including epilepsy with cognitive impairment) and accidents accounted for most of the deaths, and it was not possible to determine whether autism « per se » actually carries an increased mortality risk.
13. Golan O, Ashwin E, Granader Y, McClintock S, Day K, Leggett V, Baron-Cohen S. {{Enhancing emotion recognition in children with autism spectrum conditions: an intervention using animated vehicles with real emotional faces}}. {J Autism Dev Disord} (Mar);40(3):269-279.
This study evaluated The Transporters, an animated series designed to enhance emotion comprehension in children with autism spectrum conditions (ASC). n = 20 children with ASC (aged 4-7) watched The Transporters everyday for 4 weeks. Participants were tested before and after intervention on emotional vocabulary and emotion recognition at three levels of generalization. Two matched control groups of children (ASC group, n = 18 and typically developing group, n = 18) were also assessed twice without any intervention. The intervention group improved significantly more than the clinical control group on all task levels, performing comparably to typical controls at Time 2. We conclude that using The Transporters significantly improves emotion recognition in children with ASC. Future research should evaluate the series’ effectiveness with lower-functioning individuals.
14. Ham HS, Bartolo A, Corley M, Swanson S, Rajendran G. {{Case report: selective deficit in the production of intransitive gestures in an individual with autism}}. {Cortex} (Mar);46(3):407-409.
15. Hodge SM, Makris N, Kennedy DN, Caviness VS, Jr., Howard J, McGrath L, Steele S, Frazier JA, Tager-Flusberg H, Harris GJ. {{Cerebellum, language, and cognition in autism and specific language impairment}}. {J Autism Dev Disord} (Mar);40(3):300-316.
We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in posterior-lateral cerebellar lobule VIIIA (right side larger in unimpaired groups, left side larger in ALI and SLI), contralateral to previous findings in inferior frontal cortex language areas. Lobule VIIA Crus I was smaller in SLI than in ALI. Vermis volume, particularly anterior I-V, was decreased in language-impaired groups. Language performance test scores correlated with lobule VIIIA asymmetry and with anterior vermis volume. These findings suggest ALI and SLI subjects show abnormalities in neurodevelopment of fronto-corticocerebellar circuits that manage motor control and the processing of language, cognition, working memory, and attention.
16. Hollander E, Chaplin W, Soorya L, Wasserman S, Novotny S, Rusoff J, Feirsen N, Pepa L, Anagnostou E. {{Divalproex sodium vs placebo for the treatment of irritability in children and adolescents with autism spectrum disorders}}. {Neuropsychopharmacology} (Mar);35(4):990-998.
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests. Irritability/aggression is a significant comorbid symptom in this population, which greatly impacts burden of care. This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD. This was a 12-week randomized, double-blind, placebo-controlled trial. All efficacy measures were obtained by an independent evaluator blinded to randomization condition and side effects. A total of 55 subjects gavetheir consent and 27 were randomized in a 1 : 1 manner (mean age 9.46+/-2.46, mean nonverbal IQ 63.3+/-23.9). Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects (increased irritability). Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, which focused on irritability. Overall, 62.5% of divalproex subjects vs 9% of placebo subjects were responders (CGI-irritability OR: 16.7, Fisher’s exact p=0.008). A statistically significant improvement was also noted on the ABC-Irritability subscale (p=0.048). There was a trend for responders to have higher valproate blood levels compared with nonresponders. This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted.
17. Kopp S, Beckung E, Gillberg C. {{Developmental coordination disorder and other motor control problems in girls with autism spectrum disorder and/or attention-deficit/hyperactivity disorder}}. {Res Dev Disabil} (March – April);31(2):350-361.
Examine the rate, predictors, and effect on daily life skills of developmental coordination disorder (DCD) and other motor control difficulties in school age girls with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD), in preschool age girls with ASD referred to a neuropsychiatric clinic, and in a community sample of school age girls. The girls (131 in total) were examined with standardised test of motor function and parent interviews and questionnaires. The school girls were compared with 57 age-and IQ-matched girls from the community. DCD was diagnosed in 25% of clinic school girls with ASD, in 32% of those with ADHD, and in 80% of the clinic preschool girls with ASD. Parents reported more motor problems in the school age clinic group. Agreement between a brief motor screening test and a full comprehensive motor examination was moderate to good in the clinic group. Young age, autistic symptomatology, and low performance IQ predicted more motor coordination problems. Motor coordination problems were related to lower ability in daily life skills even when the effect of PIQ was controlled for. A large minority of school girls with ASD and/or ADHD, and a majority of preschool girls with ASD meet full diagnostic criteria for DCD. Their motor problems contribute to reduced activity in daily life even when the effects of IQ have been partialled out.
18. Matson JL, Mahan S, Hess JA, Fodstad JC. {{Effect of developmental quotient on symptoms of inattention and impulsivity among toddlers with Autism Spectrum Disorders}}. {Res Dev Disabil} (March – April);31(2):464-469.
The effect of developmental quotient on symptoms of inattention and impulsivity was examined among 198 toddlers with Autism Spectrum Disorders. There were two levels of developmental quotient: (1) low (less than or equal to 70; n=80), and (2) typical (greater than 70; n=118). Symptoms of inattention and impulsivity were assessed using 14 items that comprise the BISCIUT-Part 2 inattention/impulsivity subscale. There was no significant effect of developmental quotient on these items representing inattention and impulsivity when severity of Autism Spectrum Disorder symptoms was controlled for. However, the covariate, severity of Autism Spectrum Disorder symptoms, was significantly related to 12 of the 14 items. Percent endorsement of impairment of symptoms relating to inattention and impulsivity for the low and typical developmental quotient groups is also listed. Implications of the results are also discussed.
19. McCarthy J, Hemmings C, Kravariti E, Dworzynski K, Holt G, Bouras N, Tsakanikos E. {{Challenging behavior and co-morbid psychopathology in adults with intellectual disability and autism spectrum disorders}}. {Res Dev Disabil} (March – April);31(2):362-366.
We investigated the relationship between challenging behavior and co-morbid psychopathology in adults with intellectual disability (ID) and autism spectrum disorders (ASDs) (N=124) as compared to adults with ID only (N=562). All participants were first time referrals to specialist mental health services and were living in community settings. Clinical diagnoses were based on ICD-10 criteria and presence of challenging behavior was assessed with the Disability Assessment Schedule (DAS-B). The analyses showed that ASD diagnosis was significantly associated with male gender, younger age and lower level of ID. Challenging behavior was about four times more likely in adults with ASD as compared to non-ASD adults. In those with challenging behavior, there were significant differences in co-morbid psychopathology between ASD and non-ASD adults. However, after controlling for level of ID, gender and age, there was no association between co-morbid psychopathology and presence of challenging behavior. Overall, the results suggest that presence of challenging behavior is independent from co-morbid psychopathology in adults with ID and ASD.
20. McCleery JP, Ceponiene R, Burner KM, Townsend J, Kinnear M, Schreibman L. {{Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders}}. {J Child Psychol Psychiatry} (Mar 1);51(3):277-286.
Background: Autism is a pervasive developmental disorder characterized by deficits in social-emotional, social-communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension. However, it is not known whether these semantic deficits are confined to the verbal domain or represent a more general problem with semantic processing. The focus of the current study was to investigate verbal and meaningful nonverbal semantic processing in high-functioning children with autism (mean age = 5.8 years) using event-related potentials (ERPs). Method: ERPs were recorded while children attended to semantically matching and mismatching picture-word and picture-environmental sound pairs. Results: ERPs of typically developing children exhibited evidence of semantic incongruency detection in both the word and environmental sound conditions, as indexed by elicitation of an N400 effect. In contrast, children with ASD showed an N400 effect in the environmental sound condition but not in the word condition. Conclusions: These results provide evidence for a deficiency in the automatic activation of semantic representations in children with ASD, and suggest that this deficit is somewhat more selective to, or more severe in, the verbal than the nonverbal domain.
21. Monk CS, Weng SJ, Wiggins JL, Kurapati N, Louro HM, Carrasco M, Maslowsky J, Risi S, Lord C. {{Neural circuitry of emotional face processing in autism spectrum disorders}}. {J Psychiatry Neurosci} (Mar);35(2):105-114.
Background: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. Methods: Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. Results: In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. Limitations: The small sample size may have affected our ability to detect additional group differences. Conclusion: When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.
22. Mostafa GA, Al Shehab A, Fouad NR. {{Frequency of CD4+CD25high Regulatory T Cells in the Peripheral Blood of Egyptian Children With Autism}}. {J Child Neurol} (Mar);25(3):328-335.
Autoimmunity may have a role in autism, although the origins of autoimmunity in autism are unknown. CD4( +)CD25(high) regulatory T cells play an important role in the establishment of immunological self-tolerance, thereby preventing autoimmunity. The authors are the first to study the frequency of CD4(+)CD25( high) regulatory T cells in the blood of 30 autistic and 30 age- and sex-matched healthy children. Patients with autism had significantly lower frequency of CD4(+)CD25(high) regulatory T cells than healthy children (P < .001). These cells were deficient in 73.3% of children with autism. Autistic patients with allergic manifestations (40%) and those with a family history of autoimmunity (53.3%) had a significantly lower frequency of CD4(+)CD25(high) regulatory T cells than those without (P < .01 and P < .001, respectively). In conclusion, CD4(+)CD25( high) regulatory T cells are deficient in many children with autism. Deficiency of these cells may contribute to autoimmunity in a subgroup of children with autism. Consequently, CD4(+)CD25(high) regulatory T cells could be new potential therapeutic targets in these patients.
23. Oosterling IJ, Wensing M, Swinkels SH, van der Gaag RJ, Visser JC, Woudenberg T, Minderaa R, Steenhuis MP, Buitelaar JK. {{Advancing early detection of autism spectrum disorder by applying an integrated two-stage screening approach}}. {J Child Psychol Psychiatry} (Mar 1);51(3):250-258.
Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence base for this approach. Methods: The integrated early detection programme encompassed: 1) training relevant professionals to recognise early signs of autism and to use the Early Screening of Autistic Traits Questionnaire (ESAT; Dietz, Swinkels et al., 2006; Swinkels, van Daalen, van Engeland, & Buitelaar, 2006), 2) using a specific referral protocol, and 3) building a multidisciplinary diagnostic team. The programme was evaluated in a controlled study involving children in two regions (N = 2793, range 0-11 years). The main outcome variables were a difference in mean age at ASD diagnosis and a difference in the proportion of children diagnosed before 36 months. Results: ASD was diagnosed 21 months (95% CI 9.6, 32.4) earlier in the experimental region than in the control region during the follow-up period, with the mean age at ASD diagnosis decreasing by 19.5 months (95% CI 10.5, 28.5) from baseline in the experimental region. Children from the experimental region were 9.4 times (95% CI 2.1, 41.3) more likely than children from the control region to be diagnosed before age 36 months after correction for baseline measurements. Most of these early diagnosed children had narrowly defined autism with mental retardation. Conclusions: The integrated early detection programme appears to be clinically relevant and led to the earlier detection of ASD, mainly in children with a low IQ.
24. Ozgen HM, Hop JW, Hox JJ, Beemer FA, van Engeland H. {{Minor physical anomalies in autism: a meta-analysis}}. {Mol Psychiatry} (Mar);15(3):300-307.
Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences play a causal role. Despite the compelling evidence for a strong heritability, the etiology and molecular mechanisms underlying autism remain unclear. High phenotypic variability and genetic heterogeneity confounds the identification of susceptibility genes. The lack of robust indicators to tackle this complexity in autism has led researchers to seek for novel diagnostic tools to create homogenous subgroups. Several studies have indicated that patients with autism have higher rates of minor physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however, the results have been inconsistent. Using the cumulative data from seven studies on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data provide evidence of a large mean effect size and statistical significance for MPAs in autism. It covers the studies using multiple research methods till June 2007. The current results from seven studies suggested a significant association of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide the strongest evidence to date about the close association between MPAs and autism. Our results emphasize the importance of MPAs in the identification of heterogeneity in autism and suggest that the success of future autism genetics research will be exploited by the use of MPAs. Implications for the design of future studies on MPAs in autism are discussed and suggestions for further investigation of these important markers are proposed. Clarifying this relation might improve understanding of risk factors and molecular mechanisms in autism.
25. Posserud M, Lundervold AJ, Lie SA, Gillberg C. {{The prevalence of autism spectrum disorders: impact of diagnostic instrument and non-response bias}}. {Soc Psychiatry Psychiatr Epidemiol} (Mar);45(3):319-327.
BACKGROUND: A large part of the variability in rates of autism spectrum disorders (ASD) across studies is non-aetiologic, and can be explained by differences in diagnostic criteria, case-finding method, and other issues of study design. AIM: To investigate the effects on ASD prevalence of two methodological issues; non-response bias and case ascertainment. We compared the findings of using a semi-structured parent interview versus in-depth clinical assessment, including an ASD specific interview. We further explored whether including information on non-responders affected the ASD prevalence estimate. METHOD: A total population of 7- to 9-year olds (N = 9,430) was screened for ASD with the autism spectrum screening questionnaire (ASSQ) in the Bergen Child Study (BCS). Children scoring above the 98th percentile on parent and/or teacher ASSQ were invited to participate in the second and subsequently in the third phase of the BCS where they were assessed for ASD using the Development and Well-Being Assessment (DAWBA), and the Diagnostic Interview for Social and Communication disorders (DISCO), respectively. RESULTS: Clinical assessment using DISCO confirmed all DAWBA ASD cases, but also diagnosed additional cases. DISCO-generated minimum prevalence for ASD was 0.21%, whereas estimated prevalence was 0.72%, increasing to 0.87% when adjusting for non-responders. The DAWBA estimate for the same population was 0.44%. CONCLUSION: Large variances in prevalence rates across studies can be explained by methodological differences. Both information about assessment method and non-response are crucial when interpreting prevalence rates of ASD.
26. Rodman JL, Gilbert KA, Grove AB, Cunningham M, Levenson S, Wajsblat L. {{Efficacy of brief quantitative measures of play for screening for autism spectrum disorders}}. {J Autism Dev Disord} (Mar);40(3):325-333.
Quick and effective screening measures are needed for detecting Autism Spectrum Disorder (ASD). Thirty typically developing children and 30 children with ASD aged 24-68 months were used. This study explored if the ASD group would exhibit less object exploration, diversity of play, and turn-taking than the typically developing group. Older children with ASD performed less turn-taking. On all other measures, IQ accounted for more of the difference between groups than diagnosis. Implications of these results for future research are discussed.
27. Rosenberg RE, Mandell DS, Farmer JE, Law JK, Marvin AR, Law PA. {{Psychotropic medication use among children with autism spectrum disorders enrolled in a national registry, 2007-2008}}. {J Autism Dev Disord} (Mar);40(3):342-351.
Patterns of current psychotropic medication use among 5,181 children with autism spectrum disorders (ASD) enrolled in a Web-based registry were examined. Overall, 35% used at least one psychotropic medication, most commonly stimulants, neuroleptics, and/or antidepressants. Those who were uninsured or exclusively privately insured were less likely to use >or=3 medications than were those insured by Medicaid. Psychiatrists and neurologists prescribed the majority of psychotropic medications. In multivariate analysis, older age, presence of intellectual disability or psychiatric comorbidity, and residing in a poorer county or in the South or Midwest regions of the United States increased the odds of psychotropic medication use. Factors external to clinical presentation likely affect odds of psychotropic medication use among children with ASD.
28. Silverman JL, Tolu SS, Barkan CL, Crawley JN. {{Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP}}. {Neuropsychopharmacology} (Mar);35(4):976-989.
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two suggested treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums, and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR after treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism.
29. Spek AA, Scholte EM, Van Berckelaer-Onnes IA. {{Theory of mind in adults with HFA and Asperger syndrome}}. {J Autism Dev Disord} (Mar);40(3):280-289.
Theory of mind was assessed in 32 adults with HFA, 29 adults with Asperger syndrome and 32 neurotypical adults. The HFA and Asperger syndrome groups were impaired in performance of the Strange stories test and the Faux-pas test and reported more theory of mind problems than the neurotypical adults. The three groups did not differ in performance of the Eyes test. Furthermore, correlations between the Eyes test and the three other theory of mind tests were low or absent. Therefore one can question the ability of the Eyes test to measure theory of mind. Of all theory of mind tests used, the self-report questionnaire had the largest discriminating power in differentiating the two disorder groups from the neurotypical group.
30. Tanweer T, Rathbone CJ, Souchay C. {{Autobiographical memory, autonoetic consciousness, and identity in Asperger syndrome}}. {Neuropsychologia} (Mar);48(4):900-908.
Previous results from research on individuals with Asperger syndrome (AS) suggest a diminished ability for recalling episodic autobiographical memory (AM). The primary aim of this study was to explore autobiographical memory in individuals with Asperger syndrome and specifically to investigate whether memories in those with AS are characterized by fewer episodic ‘remembered’ events (due to a deficit in autonoetic consciousness). A further aim was to examine whether such changes in AM might also be related to changes in identity, due to the close relationship between memory and the self and to the established differences in self-referential processes in AS. Eleven adults with AS and fifteen matched comparison participants were asked to recall autobiographical memories from three lifetime periods and for each memory to give either a remember response (autonoetic consciousness) or a know response (noetic consciousness). The pattern of results shows that AS participants recalled fewer memories and that these memories were more often rated as known, compared to the comparison group. AS participants also showed differences in reported identity, generating fewer social identity statements and more abstract, trait-linked identities. The data support the view that differences in both memory and reported personal identities in AS are characterized by a lack of specificity.
31. Wachtel LE, Griffin M, Reti IM. {{Electroconvulsive therapy in a man with autism experiencing severe depression, catatonia, and self-injury}}. {J Ect} (Mar);26(1):70-73.
We report the successful use of electroconvulsive therapy in a 19-year-old man with autism and mild mental retardation who developed severe depression with repeated suicide attempts, multiple symptoms of catatonia, and life-threatening repetitive self-injurious behaviors. After 3 years of failed psychotropic and behavioral interventions in inpatient settings, the patient demonstrated excellent remission of symptoms with bilateral electroconvulsive therapy.
32. White SW, Albano AM, Johnson CR, Kasari C, Ollendick T, Klin A, Oswald D, Scahill L. {{Development of a cognitive-behavioral intervention program to treat anxiety and social deficits in teens with high-functioning autism}}. {Clin Child Fam Psychol Rev} (Mar);13(1):77-90.
Anxiety is a common co-occurring problem among young people with autism spectrum disorders (ASD). Characterized by deficits in social interaction, communication problems, and stereotyped behavior and restricted interests, this group of disorders is more prevalent than previously realized. When present, anxiety may compound the social deficits of young people with ASD. Given the additional disability and common co-occurrence of anxiety in ASD, we developed a manual-based cognitive-behavioral treatment program to target anxiety symptoms as well as social skill deficits in adolescents with ASD [Multimodal Anxiety and Social Skills Intervention: MASSI]. In this paper, we describe the foundation, content, and development of MASSI. We also summarize data on treatment feasibility based on a pilot study that implemented the intervention.
33. Williams D, Happe F. {{Representing intentions in self and other: studies of autism and typical development}}. {Dev Sci} (Mar);13(2):307-319.
Two experiments were conducted to explore the extent to which individuals with Autism Spectrum Disorder (ASD), as well as young typically developing (TD) children, are explicitly aware of their own and others’ intentions. In Experiment 1, participants with ASD were significantly less likely than age- and ability-matched comparison participants to correctly recognize their own knee-jerk reflex movements as unintentional. Performance on this knee-jerk task was associated with performance on measures of false belief understanding, independent of age and verbal ability, in both participants with ASD and TD children. In Experiment 2, participants with ASD were significantly less able than comparison participants to correctly recognize their own or another person’s mistaken actions as unintended, in a ‘Transparent Intentions’ task (Russell & Hill, 2001; Russell, Hill & Franco, 2001). Performance on aspects of the Transparent Intentions task was associated with performance on measures of false belief understanding, independent of age and verbal ability, in both participants with ASD and TD children. This study suggests that individuals with ASD have a diminished awareness of their own and others’ intentions and that this diminution is associated with other impairments in theory of mind.
34. Yechiam E, Arshavsky O, Shamay-Tsoory SG, Yaniv S, Aharon J. {{Adapted to explore: reinforcement learning in Autistic Spectrum Conditions}}. {Brain Cogn} (Mar);72(2):317-324.
Recent studies have recorded a tendency of individuals with Autism Spectrum Conditions (ASC) to continually change their choices in repeated choice tasks. In the current study we examine if this finding implies that ASC individuals have a cognitive style that facilitates exploration and discovery. Six decision tasks were administered to adolescents with ASC and matched controls. Significant differences in shifting between choice options appeared in the Iowa Gambling task (Bechara, Damasio, Damasio, & Anderson, 1994). A formal cognitive modeling analysis demonstrated that for about half of the ASC participants the adaptation process did not conform to the standard reinforcement learning model. These individuals were only coarsely affected by choice-outcomes, and were more influenced by the exploratory value of choices, being attracted to previously un-explored alternatives. An examination of the five simpler decision tasks where the advantageous option was easier to determine showed no evidence of this pattern, suggesting that the shifting choice pattern is not an uncontrollable tendency independent of task outcomes. These findings suggest that ASC individuals have a unique adaptive learning style, which may be beneficial is some learning environment but maladaptive in others, particularly in social contexts.
35. Zhao Y, Fung C, Shin D, Shin BC, Thamotharan S, Sankar R, Ehninger D, Silva A, Devaskar SU. {{Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders}}. {Mol Psychiatry} (Mar);15(3):286-299.
Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.
