1. Brown A, Chow D, Murakami S, Goh W, Perreira A, Kwee S, Sil P, Leroy M. {{Possible gastrointestinal symptoms in a subset of children with autism}}. {Expert Rev Gastroenterol Hepatol} (Apr);4(2):125-127.
2. Castermans D, Volders K, Crepel A, Backx L, De Vos R, Freson K, Meulemans S, Vermeesch JR, Schrander-Stumpel CT, De Rijk P, Del-Favero J, Van Geet C, Van De Ven WJ, Steyaert JG, Devriendt K, Creemers JW. {{SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles}}. {Hum Mol Genet} (Apr 1);19(7):1368-1378.
Autism is a neurodevelopmental disorder characterized by impaired social reciprocity, impaired communication and stereotypical behaviors. Despite strong evidence for a genetic basis, few susceptibility genes have been identified. Here, we describe the positional cloning of SCAMP5, CLIC4 and PPCDC as candidate genes for autism, starting from a person with idiopathic, sporadic autism carrying a de novo chromosomal translocation. One of these genes, SCAMP5 is silenced on the derivative chromosome, and encodes a brain-enriched protein involved in membrane trafficking, similar to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold increase in stimulated secretion of large dense-core vesicles (LDCVs), while overexpression suppressed secretion. Moreover, ultrastructural analysis of blood platelets from the patients with haploinsufficieny of one of the three candidate genes, showed morphological abnormalities of dense-core granules, which closely resemble LDCVs. Taken together, this study shows that in three independent patients with autism three different negative regulators of LDCV secretion are affected, respectively, suggesting that in at least a subgroup of patients the regulation of neuronal vesicle trafficking may be involved in the pathogenesis of autism.
3. Cobb S, Guy J, Bird A. {{Reversibility of functional deficits in experimental models of Rett syndrome}}. {Biochem Soc Trans} (Apr);38(2):498-506.
Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiology. Recent evidence suggests that reactivation of endogenous Mecp2 in young and adult mice can reverse aspects of RTT-like pathology. In the current perspective, we discuss these findings as well as other genetic, pharmacological and environmental interventions that attempt phenotypic rescue in RTT. We believe these studies provide valuable insights into the tractability of RTT and related conditions and are useful pointers for the development of future therapeutic strategies.
4. Coury D. {{Medical treatment of autism spectrum disorders}}. {Curr Opin Neurol} (Apr);23(2):131-136.
PURPOSE OF REVIEW: There are several common medical conditions occurring in people with autism spectrum disorders (ASD) that can benefit from treatment and can in turn improve the health and quality of life of people with ASD. This review will primarily focus on these medical comorbidities, with a brief review of potential future treatments. RECENT FINDINGS: There continues to be disagreement regarding the exact prevalence and etiological significance of gastrointestinal conditions, epilepsy and other abnormal electroencephalographic findings, and sleep problems. It is not clear whether gastrointestinal conditions occur more frequently than in typically developing children, and whether there are distinct conditions that occur more often in ASD than in non-ASD populations. Abnormal electroencephalographic findings have been reported in up to 60% of children with ASD, and some believe that these abnormalities may be responsible for parts of the ASD phenotype. Sleep problems are reported more frequently than in the general population, and effective treatments are available. Future medical treatments for ASD may be directed at underlying core symptoms and have greater impact than today’s symptomatic approach. SUMMARY: Further research in these areas is needed to better guide diagnosis and treatment of a variety of medical conditions experienced by people with ASD.
5. Couture SM, Penn DL, Losh M, Adolphs R, Hurley R, Piven J. {{Comparison of social cognitive functioning in schizophrenia and high functioning autism: more convergence than divergence}}. {Psychol Med} (Apr);40(4):569-579.
BACKGROUND: Individuals with schizophrenia and individuals with high-functioning autism (HFA) seem to share some social, behavioral and biological features. Although marked impairments in social cognition have been documented in both groups, little empirical work has compared the social cognitive functioning of these two clinical groups. METHOD: Forty-four individuals with schizophrenia, 36 with HFA and 41 non-clinical controls completed a battery of social cognitive measures that have been linked previously to specific brain regions. RESULTS: The results indicate that the individuals with schizophrenia and HFA were both impaired on a variety of social cognitive tasks relative to the non-clinical controls, but did not differ from one another. When individuals with schizophrenia were divided into negative symptom and paranoid subgroups, exploratory analyses revealed that individuals with HFA may be more similar, in terms of the pattern of social cognition impairments, to the negative symptom group than to the paranoia group. CONCLUSIONS: Our findings provide further support for similarities in social cognition deficits between HFA and schizophrenia, which have a variety of implications for future work on gene-brain-behavior relationships.
6. Dawson G. {{Recent advances in research on early detection, causes, biology, and treatment of autism spectrum disorders}}. {Curr Opin Neurol} (Apr);23(2):95-96.
7. Derecki NC, Privman E, Kipnis J. {{Rett syndrome and other autism spectrum disorders–brain diseases of immune malfunction?}}. {Mol Psychiatry} (Apr);15(4):355-363.
Neuroimmunology was once referred to in terms of its pathological connotation only and was generally understood as covering the deleterious involvement of the immune system in various diseases and disorders of the central nervous system (CNS). However, our conception of the function of the immune system in the structure, function, and plasticity of the CNS has undergone a sea change after relevant discoveries over the past two decades, and continues to be challenged by more recent studies of neurodevelopment and cognition. This review summarizes the recent advances in understanding of immune-system participation in the development and functioning of the CNS under physiological conditions. Considering as an example Rett syndrome a devastating neurodevelopmental disease, we offer a hypothesis that might help to explain the part played by immune cells in its etiology, and hence suggests that the immune system might be a feasible therapeutic target for alleviation of some of the symptoms of this and other autism spectrum disorders.
8. Dichter GS, Radonovich KJ, Turner-Brown LM, Lam KS, Holtzclaw TN, Bodfish JW. {{Performance of children with autism spectrum disorders on the dimension-change card sort task}}. {J Autism Dev Disord} (Apr);40(4):448-456.
Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to reflect impaired executive functions. In the present study, we investigated the performance of 6-17-year-old children with and without an autism spectrum disorder on a dimension-change card sort task that explicitly indicated sorting rules on every trial. Diagnostic groups did not differ in speed of responses after the first rule switch or in speed or accuracy on blocks with mixed versus single sort rules. However, performance of the ASD group was significantly slower and less accurate overall than the typically-developing group. Furthermore, within the ASD group, poorer DCCS task performance did not predict more severe autism symptoms. Implications for the executive dysfunction theory of autism are discussed.
9. Didden R, Korzilius H, Smeets E, Green VA, Lang R, Lancioni GE, Curfs LM. {{Communication in Individuals with Rett Syndrome: an Assessment of Forms and Functions}}. {J Dev Phys Disabil} (Apr);22(2):105-118.
In the present study we assessed the forms and functions of prelinguistic communicative behaviors for 120 children and adults with Rett syndrome using the Inventory of Potential Communicative Acts (IPCA) (Sigafoos et al. Communication Disorders Quarterly 21:77-86, 2000a). Informants completed the IPCA and the results were analysed to provide a systematic inventory and objective description of the communicative forms and functions present in each individual’s repertoire. Results show that respondents reported a wide variety of communicative forms and functions. By far most girls used prelinguistic communicative behaviors of which eye contact/gazing was the most common form. The most often endorsed communicative functions were social convention, commenting, answering, requesting and choice-making. Problematic topographies (e.g., self-injury, screaming, non-compliance) were being used for communicative purposes in 10 to 41% of the sample. Exploratory analyses revealed that several communicative forms and functions were related to living environment, presence/absence of epilepsy, and age. That is, higher percentages of girls who showed some forms/functions were found in those who lived at home, who had no epilepsy and who were relatively young.
10. Glickman G. {{Circadian rhythms and sleep in children with autism}}. {Neurosci Biobehav Rev} (Apr);34(5):755-768.
A growing body of research has identified significant sleep problems in children with autism. Disturbed sleep-wake patterns and abnormal hormone profiles in children with autism suggest an underlying impairment of the circadian timing system. Reviewing normal and dysfunctional relationships between sleep and circadian rhythms will enable comparisons to sleep problems in children with autism, prompt a reexamination of existing literature and offer suggestions for future inquiry. In addition, sleep and circadian rhythms continue to change over the course of development even in typical, healthy humans. Therefore, exploring the dynamic relationship between circadian rhythms and sleep throughout development provides valuable insight into those sleep problems associated with autism. Ultimately, a better understanding of sleep and circadian rhythms in children with autism may help guide appropriate treatment strategies and minimize the negative impact of these disturbances on both the children and their families.
11. Goines P, Van de Water J. {{The immune system’s role in the biology of autism}}. {Curr Opin Neurol} (Apr);23(2):111-117.
PURPOSE OF REVIEW: The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. RECENT FINDINGS: The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed toward fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. Although studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. SUMMARY: In summary, the exciting research regarding the role of the immune system in autism spectrum disorders may have profound implications for diagnosis and treatment of this devastating disease.
12. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB. {{Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders}}. {Biol Psychiatry} (Apr 1);67(7):692-694.
BACKGROUND: A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. METHODS: In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger’s Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. RESULTS: In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. CONCLUSIONS: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders.
13. Herbert MR. {{Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders}}. {Curr Opin Neurol} (Apr);23(2):103-110.
PURPOSE OF REVIEW: This review presents a rationale and evidence for contributions of environmental influences and environmentally vulnerable physiology to autism spectrum disorders (ASDs). RECENT FINDINGS: Recent studies suggest a substantial increase in ASD prevalence above earlier Centers for Disease Control figures of one in 150, only partly explicable by data artifacts, underscoring the possibility of environmental contributors to increased prevalence. Some gene variants in ASD confer altered vulnerability to environmental stressors and exposures. De-novo mutations and advanced parental age as a risk factor for ASD also suggest a role for environment. Systemic and central nervous system pathophysiology, including oxidative stress, neuroinflammation, and mitochondrial dysfunction can be consistent with a role for environmental influence (e.g. from air pollution, organophosphates, heavy metals) in ASD, and some of the underlying biochemical disturbances (such as abnormalities in glutathione, a critical antioxidant and detoxifier) can be reversed by targeted nutritional interventions. Dietary factors and food contaminants may contribute risk. Improvement and loss of diagnosis in some with ASD suggest brain circuitry amenable to environmental modulation. SUMMARY: Prevalence, genetic, exposure, and pathophysiological evidence all suggest a role for environmental factors in the inception and lifelong modulation of ASD. This supports the need for seeking targets for early and ongoing medical prevention and treatment of ASD.
14. Hobson RP, Garcia-Perez RM, Lee A. {{Person-centred (deictic) expressions and autism}}. {J Autism Dev Disord} (Apr);40(4):403-415.
We employed semi-structured tests to determine whether children with autism produce and comprehend deictic (person-centred) expressions such as ‘this’/’that’, ‘here’/’there’ and ‘come’/’go’, and whether they understand atypical non-verbal gestural deixis in the form of directed head-nods to indicate location. In Study 1, most participants spontaneously produced deictic terms, often in conjunction with pointing. Yet only among children with autism were there participants who referred to a location that was distal to themselves with the terms ‘this’ or ‘here’, or made atypical points with unusual precision, often lining-up with an eye. In Study 2, participants with autism were less accurate in responding to instructions involving contrastive deictic terms, and fewer responded accurately to indicative head nods.
15. Hyde KL, Samson F, Evans AC, Mottron L. {{Neuroanatomical differences in brain areas implicated in perceptual and other core features of autism revealed by cortical thickness analysis and voxel-based morphometry}}. {Hum Brain Mapp} (Apr);31(4):556-566.
Autism spectrum disorder is a complex neurodevelopmental variant thought to affect 1 in 166 [Fombonne (2003): J Autism Dev Disord 33:365-382]. Individuals with autism demonstrate atypical social interaction, communication, and repetitive behaviors, but can also present enhanced abilities, particularly in auditory and visual perception and nonverbal reasoning. Structural brain differences have been reported in autism, in terms of increased total brain volume (particularly in young children with autism), and regional gray/white matter differences in both adults and children with autism, but the reports are inconsistent [Amaral et al. (2008): Trends Neurosci 31:137-145]. These inconsistencies may be due to differences in diagnostic/inclusion criteria, and age and Intelligence Quotient of participants. Here, for the first time, we used two complementary magnetic resonance imaging techniques, cortical thickness analyses, and voxel-based morphometry (VBM), to investigate the neuroanatomical differences between a homogenous group of young adults with autism of average intelligence but delayed or atypical language development (often referred to as « high-functioning autism »), relative to a closely matched group of typically developing controls. The cortical thickness and VBM techniques both revealed regional structural brain differences (mostly in terms of gray matter increases) in brain areas implicated in social cognition, communication, and repetitive behaviors, and thus in each of the core atypical features of autism. Gray matter increases were also found in auditory and visual primary and associative perceptual areas. We interpret these results as the first structural brain correlates of atypical auditory and visual perception in autism, in support of the enhanced perceptual functioning model [Mottron et al. (2006): J Autism Dev Disord 36:27-43].
16. Jiao Y, Chen R, Ke X, Chu K, Lu Z, Herskovits EH. {{Predictive models of autism spectrum disorder based on brain regional cortical thickness}}. {Neuroimage} (Apr 1);50(2):589-599.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide phenotypic range, often affecting personality and communication. Previous voxel-based morphometry (VBM) studies of ASD have identified both gray- and white-matter volume changes. However, the cerebral cortex is a 2-D sheet with a highly folded and curved geometry, which VBM cannot directly measure. Surface-based morphometry (SBM) has the advantage of being able to measure cortical surface features, such as thickness. The goals of this study were twofold: to construct diagnostic models for ASD, based on regional thickness measurements extracted from SBM, and to compare these models to diagnostic models based on volumetric morphometry. Our study included 22 subjects with ASD (mean age 9.2+/-2.1 years) and 16 volunteer controls (mean age 10.0+/-1.9 years). Using SBM, we obtained regional cortical thicknesses for 66 brain structures for each subject. In addition, we obtained volumes for the same 66 structures for these subjects. To generate diagnostic models, we employed four machine-learning techniques: support vector machines (SVMs), multilayer perceptrons (MLPs), functional trees (FTs), and logistic model trees (LMTs). We found that thickness-based diagnostic models were superior to those based on regional volumes. For thickness-based classification, LMT achieved the best classification performance, with accuracy=87%, area under the receiver operating characteristic (ROC) curve (AUC)=0.93, sensitivity=95%, and specificity=75%. For volume-based classification, LMT achieved the highest accuracy, with accuracy=74%, AUC=0.77, sensitivity=77%, and specificity=69%. The thickness-based diagnostic model generated by LMT included 7 structures. Relative to controls, children with ASD had decreased cortical thickness in the left and right pars triangularis, left medial orbitofrontal gyrus, left parahippocampal gyrus, and left frontal pole, and increased cortical thickness in the left caudal anterior cingulate and left precuneus. Overall, thickness-based classification outperformed volume-based classification across a variety of classification methods.
17. Johnson S, Hollis C, Kochhar P, Hennessy E, Wolke D, Marlow N. {{Autism spectrum disorders in extremely preterm children}}. {J Pediatr} (Apr);156(4):525-531 e522.
OBJECTIVES: To investigate the prevalence, correlates, and antecedents of autism spectrum disorders (ASD) in extremely preterm children. STUDY DESIGN: We conducted a prospective study of all births <26 weeks gestation in the United Kingdom and Ireland in 1995. Of 307 survivors at 11 years, 219 (71%) were assessed and compared with 153 term-born classmates. Parents completed the Social Communication Questionnaire (SCQ) to assess autism spectrum symptoms, and ASD were diagnosed by using a psychiatric evaluation. An IQ test and clinical evaluation were also administered. Longitudinal outcome data were available for extremely preterm children. RESULTS: Extremely preterm children had significantly higher SCQ scores than classmates (mean difference, 4.6 points; 95% CI, 3.4-5.8). Sixteen extremely preterm children (8%) were assigned an ASD diagnosis, compared with none of the classmates. By hospital discharge, male sex, lower gestation, vaginal breech delivery, abnormal cerebral ultrasound scanning results, and not having had breast milk were independently associated with autism spectrum symptoms. By 6 years, independent associates were cognitive impairment, inattention and peer problems, withdrawn behavior at 2.5 years, and not having had breast milk. CONCLUSIONS: Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood. These symptoms and disorders were associated with neurocognitive outcomes, suggesting that ASD may result from abnormal brain development in this population.
18. Kasari C, Lawton K. {{New directions in behavioral treatment of autism spectrum disorders}}. {Curr Opin Neurol} (Apr);23(2):137-143.
PURPOSE OF REVIEW: The review explores current trends in the behavioral intervention literature for children with an autism spectrum disorder (ASD) during 2008 and 2009. Noteworthy findings and intervention strategies are highlighted. Additionally, the quality of all reviewed studies is systematically evaluated. RECENT FINDINGS: During 2008 and 2009, there was nearly a quarter increase in the number of behavioral intervention studies, as well as more randomized controlled trials and approaches other than applied behavior analysis. Many of the studies investigated commonly used ASD intervention practices or novel treatments. A few were conducted with underserved populations, such as toddlers and adults with ASD. Social impairment was the focus of the largest number of intervention studies. A small percentage of studies were rated as high-quality. SUMMARY: Overall, the reviewed studies suggest that ASD-specific deficits can be improved through behavioral intervention. However, whereas progress continues to be made in our understanding of effective treatments for children with ASD, confidence in these findings would be improved with higher-quality studies.
19. Kenworthy L, Case L, Harms MB, Martin A, Wallace GL. {{Adaptive behavior ratings correlate with symptomatology and IQ among individuals with high-functioning autism spectrum disorders}}. {J Autism Dev Disord} (Apr);40(4):416-423.
Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD group, adaptive communication skills were positively related to IQ while global adaptive functioning was negatively associated with autism symptomatology. Autistic behavior ratings related negatively to ABAS scores in the TD but not the ASD group. This investigation demonstrates: the utility of an adaptive functioning checklist for capturing impairments, even in high-functioning individuals with ASD; and that a relationship between social abilities and autism exists independently of intelligence.
20. Landrigan PJ. {{What causes autism? Exploring the environmental contribution}}. {Curr Opin Pediatr} (Apr);22(2):219-225.
PURPOSE OF REVIEW: Autism is a biologically based disorder of brain development. Genetic factors–mutations, deletions, and copy number variants–are clearly implicated in causation of autism. However, they account for only a small fraction of cases, and do not easily explain key clinical and epidemiological features. This suggests that early environmental exposures also contribute. This review explores this hypothesis. RECENT FINDINGS: Indirect evidence for an environmental contribution to autism comes from studies demonstrating the sensitivity of the developing brain to external exposures such as lead, ethyl alcohol and methyl mercury. But the most powerful proof-of-concept evidence derives from studies specifically linking autism to exposures in early pregnancy – thalidomide, misoprostol, and valproic acid; maternal rubella infection; and the organophosphate insecticide, chlorpyrifos. There is no credible evidence that vaccines cause autism. SUMMARY: Expanded research is needed into environmental causation of autism. Children today are surrounded by thousands of synthetic chemicals. Two hundred of them are neurotoxic in adult humans, and 1000 more in laboratory models. Yet fewer than 20% of high-volume chemicals have been tested for neurodevelopmental toxicity. I propose a targeted discovery strategy focused on suspect chemicals, which combines expanded toxicological screening, neurobiological research and prospective epidemiological studies.
21. Lind SE, Bowler DM. {{Impaired performance on see-know tasks amongst children with autism: evidence of specific difficulties with theory of mind or domain-general task factors?}}. {J Autism Dev Disord} (Apr);40(4):479-484.
It is widely assumed that children with autism have a diminished understanding of the perception-knowledge relationship, as a specific manifestation of a theory of mind (ToM) impairment. However, such a conclusion may not be justified on the basis of previous studies, which have suffered from significant methodological weaknesses. The current study aimed to avoid such problems by adopting more stringent participant matching methods, using a larger sample (N = 80), and implementing a new, more rigorous control task in order to ensure that non-ToM task factors were not confounding results. After excluding children who failed the control task, it was found that children with autism were moderately impaired in their understanding of the perception-knowledge relationship, relative to age- and verbal ability matched comparison children.
22. Loth E, Gomez JC, Happe F. {{When seeing depends on knowing: adults with Autism Spectrum Conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects}}. {Neuropsychologia} (Apr);48(5):1227-1236.
Behavioural, neuroimaging and neurophysiological approaches emphasise the active and constructive nature of visual perception, determined not solely by the environmental input, but modulated top-down by prior knowledge. For example, degraded images, which at first appear as meaningless ‘blobs’, can easily be recognized as, say, a face, after having seen the same image un-degraded. This conscious perception of the fragmented stimuli relies on top-down priming influences from systems involved in attention and mental imagery on the processing of stimulus attributes, and feature-binding [Dolan, R. J., Fink, G. R., Rolls, E., Booth, M., Holmes, A., Frackowiak, R. S. J., et al. (1997). How the brain learns to see objects and faces in an impoverished context. Nature, 389, 596-599]. In Autism Spectrum Conditions (ASC), face processing abnormalities are well-established, but top-down anomalies in various domains have also been shown. Thus, we tested two alternative hypotheses: (i) that people with ASC show overall reduced top-down modulation in visual perception, or (ii) that top-down anomalies affect specifically the perception of faces. Participants were presented with sets of three consecutive images: degraded images (of faces or objects), corresponding or non-corresponding grey-scale photographs, and the same degraded images again. In a passive viewing sequence we compared gaze times (an index of focal attention) on faces/objects vs. background before and after viewers had seen the undegraded photographs. In an active viewing sequence, we compared how many faces/objects were identified pre- and post-exposure. Behavioural and gaze tracking data showed significantly reduced effects of prior knowledge on the conscious perception of degraded faces, but not objects in the ASC group. Implications for future work on the underlying mechanisms, at the cognitive and neurofunctional levels, are discussed.
23. McCravy S, Johnson A, Wetsel MA, Konz L. {{Speak the language of autism}}. {Nurse Pract} (Apr);35(4):26-33; quiz 34.
24. Miano S, Ferri R. {{Epidemiology and management of insomnia in children with autistic spectrum disorders}}. {Paediatr Drugs} (Apr 1);12(2):75-84.
Insomnia is the predominant sleep concern in children with autistic spectrum disorder (ASD), and its nature is most likely multifactorial, with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors involved. Children with ASD experience sleep problems similar to those of typically developing children, although the prevalence is markedly higher, occurring in 44-83% of school-aged children with ASD. Caregivers usually report that insomnia is the most frequent sleep disorder, described as disorders of initiating and maintaining sleep, restless sleep, bedtime resistance, co-sleeping, alterations of sleep hygiene, and early awakenings in the morning. Many actigraphic studies have added information on sleep disorders, confirming the questionnaire findings in the majority of cases. There are relatively few polysomnographic data for ASD, compared with questionnaire studies, and most of these studies reported a reduction in total sleep time and more undifferentiated sleep in the youngest patients. These findings were associated with several sleep microstructure alterations during rapid eye movement (REM) sleep, and with non-REM (NREM) sleep microstructure changes that appeared to be related to cognitive impairment rather than to the autistic core. Moreover, few data about other less frequent sleep disorders, such as periodic limb movements disorder and obstructive sleep apnea syndrome, bruxism, and the influence of epilepsy and EEG abnormalities, are available. Both pharmacologic and behavioral interventions have been suggested for the treatment of sleep problems in autistic children. The most common types of behavioral interventions are complete extinction (removing reinforcement to reduce a behavior) and various forms of graduated extinction. Melatonin has shown promising results in the treatment of insomnia in children with ASD. Although controlled studies are limited, there are more data demonstrating the safety and effectiveness of melatonin in ASD than for other sedative/hypnotic drugs. Finally, a dual treatment for insomnia in ASDs with melatonin and behavioral techniques has been suggested. A recent study using a combination of genetic and functional experimental techniques reported evidence that low melatonin concentration caused by a primary deficit in acetylserotonin methyltransferase activity is a risk factor for ASD. Sleep problems usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Further studies, beginning at younger ages, are necessary to better investigate these aspects and the role of melatonin in insomnia in children with ASD.
25. Minshew NJ, Keller TA. {{The nature of brain dysfunction in autism: functional brain imaging studies}}. {Curr Opin Neurol} (Apr);23(2):124-130.
PURPOSE OF REVIEW: Functional magnetic resonance imaging studies have had a profound impact on the delineation of the neurobiologic basis for autism. Advances in fMRI technology for investigating functional connectivity, resting state connectivity, and a default mode network have provided further detail about disturbances in brain organization and brain-behavior relationships in autism to be reviewed in this article. RECENT FINDINGS: Recent fMRI studies have provided evidence of enhanced activation and connectivity of posterior, or parietal-occipital, networks and enhanced reliance on visuospatial abilities for visual and verbal reasoning in high functioning individuals with autism. Evidence also indicates altered activation in frontostriatal networks for cognitive control, particularly involving anterior cingulate cortex, and altered connectivity in the resting state and the default mode network. The findings suggest that the specialization of many cortical networks of the human brain has failed to develop fully in high functioning individuals with autism. SUMMARY: This research provides a growing specification of to the neurobiologic basis for this complex syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With this knowledge has come new neurobiologically based opportunities for intervention.
26. Msall ME. {{Central nervous system connectivity after extreme prematurity: understanding autistic spectrum disorder}}. {J Pediatr} (Apr);156(4):519-521.
27. Odom SL, Boyd BA, Hall LJ, Hume K. {{Evaluation of comprehensive treatment models for individuals with autism spectrum disorders}}. {J Autism Dev Disord} (Apr);40(4):425-436.
Multiple dimensions of comprehensive treatment models (CTMs) for learners with autism were evaluated in this study. The purpose of the study was to provide evaluative information upon which service providers, family members, and researchers could make decisions about model adoption, selection for a family member, or future research. Thirty CTMs were identified, with the majority based on an applied behavior analysis framework, although a substantial minority followed a developmental or relationship-based model. As a group, CTMs were strongest in the operationalization of their models, although relatively weaker in measurement of implementation, and with notable exceptions, weak in evidence of efficacy.
28. Percy AK, Lee HS, Neul JL, Lane JB, Skinner SA, Geerts SP, Annese F, Graham J, McNair L, Motil KJ, Barrish JO, Glaze DG. {{Profiling scoliosis in rett syndrome}}. {Pediatr Res} (Apr);67(4):435-439.
To understand scoliosis, related comorbidities, and phenotype-genotype correlations in individuals with Rett syndrome (RTT), the Rare Disease Clinical Research Network database for RTT was probed. Clinical evaluations included a detailed history and physical examination, comprehensive anthropometric measurements, and two quantitative measures of clinical status, Clinical Severity Scale (CSS) and motor-behavioral analysis (MBA). All data were exported to the Data Technology Coordinating Center (DTCC) at the University of South Florida. Scoliosis assessment was based on direct examination and curvature measurements by radiography (Cobb angle). Statistical analyses included univariate and multiple logistic regression models, adjusting for age at enrollment or mutation type. Scoliosis data were available from 554 classic RTT participants, mean age = 10 y (0-57 y). Scoliosis was noted in 292 (53%); mean age = 15 y with scoliosis and 6 y without. Using multiple regression analysis, MBA severity score, later acquisition, loss or absent walking, and constipation were associated with scoliosis. Two common methyl-CpG-binding protein 2 (MECP2) mutations, R294X and R306C, had reduced risk for scoliosis. These findings corroborated previous reports on scoliosis and extended understanding of comorbidities, clinical severity, and relative risk reduction for specific mutations. Clinical trial design should account for scoliosis and related factors judiciously.
29. Ploeger A, Raijmakers ME, van der Maas HL, Galis F. {{The association between autism and errors in early embryogenesis: what is the causal mechanism?}}. {Biol Psychiatry} (Apr 1);67(7):602-607.
The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development-early organogenesis-can explain this association. In humans early organogenesis is an embryonic stage, spanning Day 20 to Day 40 after fertilization, which is characterized by intense interactivity among body parts of the embryo. This implies that a single mutation or environmental disturbance affecting development at this stage can have several phenotypic effects (i.e., pleiotropic effects). Disturbances during early organogenesis can lead to many different anomalies, including limb deformities, craniofacial malformations, brain pathology, and anomalies in other organs. We reviewed the literature and found ample evidence for the association between autism and different kinds of physical anomalies, which agrees with the hypothesis that pleiotropic effects are involved in the development of autism. The proposed mechanism integrates findings from a variety of studies on autism, including neurobiological studies and studies on physical anomalies and prenatal influences on neurodevelopmental outcomes. The implication is that the origin of autism can be much earlier in embryologic development than has been frequently reported.
30. Pollmann MM, Finkenauer C, Begeer S. {{Mediators of the link between autistic traits and relationship satisfaction in a non-clinical sample}}. {J Autism Dev Disord} (Apr);40(4):470-478.
People with ASD have deficits in their social skills and may therefore experience lower relationship satisfaction. This study investigated possible mechanisms to explain whether and how autistic traits, measured with the AQ, influence relationship satisfaction in a non-clinical sample of 195 married couples. More autistic traits were associated with lower relationship satisfaction for husbands but not for wives. Multiple mediation analyses revealed that husbands’ responsiveness towards their wives, trust, and intimacy mediated this link between autistic traits and relationship satisfaction. These findings suggest that autistic traits may hamper men’s relationship satisfaction because they impede relationship-specific feelings and behavior. There was no partner-effect of autistic traits, indicating that more autistic traits do not necessarily influence the partner’s perceptions of relationship satisfaction.
31. Rubenstein JL. {{Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder}}. {Curr Opin Neurol} (Apr);23(2):118-123.
PURPOSE OF REVIEW: Molecular and genetic insights into the etiology of autism spectrum disorders are now available. The field now needs to understand how these perturbations affect development and function of the brain. RECENT FINDINGS: Herein I review the genetic mechanisms known to predispose to autism spectrum disorders, and attempt to consolidate many of these within cellular/molecular pathways that regulate development of neural systems that underlie cognition and social behaviors. In addition to the clear relationship of many susceptibility genes to activity-dependent neural responses, I propose the existence of three additional mechanisms that may contribute to autism spectrum disorders: evolutionary-driven expansion of cerebrum and cerebellar size; imbalance in the excitatory/inhibitory ratio in local and extended circuits; the hormonal effects of the male genotype. SUMMARY: Understanding these mechanisms opens the possibility to therapeutic interventions.
32. Samson AC, Hegenloh M. {{Stimulus characteristics affect humor processing in individuals with Asperger syndrome}}. {J Autism Dev Disord} (Apr);40(4):438-447.
The present paper aims to investigate whether individuals with Asperger syndrome (AS) show global humor processing deficits or whether humor comprehension and appreciation depends on stimulus characteristics. Non-verbal visual puns, semantic and Theory of Mind cartoons were rated on comprehension, funniness and the punchlines were explained. AS individuals did not differ to the control group in humor appreciation of visual puns. However, they had difficulty understanding and appreciating Theory of Mind cartoons and provided mentalistic explanations less frequently than controls suggesting that humor processing is strongly related to the cognitive requirements that the stimuli pose on the perceiver. Furthermore, AS individuals referred in all conditions more frequently to non-joke relevant details. Therefore, humor processing is also influenced by their detail-oriented processing style.
33. Senel HG. {{Parents’ views and experiences about complementary and alternative medicine treatments for their children with autistic spectrum disorder}}. {J Autism Dev Disord} (Apr);40(4):494-503.
Use of complementary and alternative medicine (CAM) treatments have been increasing for children with autistic spectrum disorder (ASD). In this study, 38 Turkish parents of children with ASD were surveyed related with their use of CAM treatments, experiences, and views for each treatment. They mentioned « Vitamins and minerals », « Special Diet », « Sensory Integration », « Other Dietary Supplements », and « Chelation » as five frequently used CAM treatments. Communication, learning, health, and behavior were the main four areas rated as « improved » after five CAM treatments. Negative sides of treatments were listed as being expensive, difficult to apply, or harmful. The parents’ views on some treatments have varied from great improvement to worse. Reported improvements were considerably higher than the negative sides of the treatments.
34. Sheppard E, Ropar D, Underwood G, van Loon E. {{Brief report: driving hazard perception in autism}}. {J Autism Dev Disord} (Apr);40(4):504-508.
This study investigated whether individuals with ASD (autistic spectrum disorders) are able to identify driving hazards, given their difficulties processing social information, Klin et al. (Archives of General Psychiatry 59: 809-816, 2002). Twenty-three adult males with ASD and 21 comparison participants viewed 10 video clips containing driving hazards. In half of the clips the source of the hazard was a visible person (social); in the other half the source was a car (non-social). Participants with ASD identified fewer social hazards than the comparison participants (U = 163.00, N = 44, p < .05) but not non-social. Participants with ASD were also slower to respond than comparison participants, F(1,40) = 4.93, p < .05. This suggests that, although people with ASD can perceive driving hazards they may have specific difficulty identifying them if they involve a person.
35. Vattikuti S, Chow CC. {{A computational model for cerebral cortical dysfunction in autism spectrum disorders}}. {Biol Psychiatry} (Apr 1);67(7):672-678.
BACKGROUND: Perturbations to the microscopic level balance between synaptic excitation and inhibition and neuron organization in the cerebral cortex are suggested to underlie autism spectrum disorder (ASD) traits. The mechanism linking these perturbations to cognitive behaviors in ASD is unknown. This study strives to bridge this gap by generating clinically testable diagnostic and pharmacological predictions based on the effect of synaptic imbalance and neuron distribution on a computational local circuit model of the cerebral cortex. METHODS: We use a computational microscopic model of the cerebral cortex that incorporates N-methyl-D-aspartate and gamma-aminobutyric acid synaptic kinetics. We employ the model circuit during model tasks similar to visually guided and gap oculomotor saccade tasks and interpret qualitative model predictions of saccade hypometria and dysmetria. We consider the effects of varying the excitatory to inhibitory synaptic balance, neuron density, and neuron clustering in this model. RESULTS: An increase of synaptic excitation over synaptic inhibition results in increased hypometria and dysmetria. Similar effects by either reduced inhibition or increased excitation suggest that a variety of pharmacological compounds can be used for both screening and medical management. On the other hand, any change to the microscopic neuron anatomy that increases the effective maximum distance between excitatory neurons decreases hypometria but has no affect on dysmetria. CONCLUSIONS: Perturbations to a computational model of a local cerebral cortical circuit can account for saccade hypometria and dysmetria reported in ASD studies. This approach may provide a direct link between cerebral cortical function and ASD behaviors.
36. Willemsen MH, Fernandez BA, Bacino CA, Gerkes E, de Brouwer AP, Pfundt R, Sikkema-Raddatz B, Scherer SW, Marshall CR, Potocki L, van Bokhoven H, Kleefstra T. {{Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome}}. {Eur J Hum Genet} (Apr);18(4):429-435.
The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.
37. Zalla T, Labruyere N, Clement A, Georgieff N. {{Predicting ensuing actions in children and adolescents with autism spectrum disorders}}. {Exp Brain Res} (Apr);201(4):809-819.
This study investigated the ability to predict others’ action in a group of children and adolescents with autism spectrum disorders (ASD) (n = 18). Their performance was compared with a group of children with mental retardation (n = 13) and a group of children with typical development (n = 19). Participants were presented with short incomplete videotaped movies showing an actor executing familiar and non-familiar actions. When asked to predict the outcome, participants with ASD produced fewer correct responses and their performance did not improve for familiar actions, as compared to both comparison groups. In addition, they committed a greater number of errors of temporal inversion. These results provide new evidence that an impaired means-end analysis process, leading to a diminished sensitivity to the sequence structure of goal-directed actions, would disrupt the ability to understand and predict others’ actions. The comprehension of abnormalities in event knowledge provides a better insight of some of the problems that individuals with ASD encounter in spontaneously understanding real-life social situations.
38. Zwaigenbaum L. {{Advances in the early detection of autism}}. {Curr Opin Neurol} (Apr);23(2):97-102.
PURPOSE OF REVIEW: Early detection and diagnosis of autism spectrum disorders (ASDs) allows opportunities for children and their families to benefit more fully from early supports and interventions. RECENT FINDINGS: Recent advances in early detection research have resulted from prospective studies of high-risk infants and large ASD screening studies conducted in community settings. With improvement in early detection of autism, exciting progress has been made in establishing the efficacy of ASD-specific interventions for toddlers as young as 18 months on the basis of controlled clinical trials. SUMMARY: There has been increasing emphasis on opportunities to link early behavioral expression to the underlying neurobiology of ASD, potentially bringing us closer to the fundamental mechanisms underlying this disorder.
