1. Almeida RA, Dickinson JE, Maybery MT, Badcock JC, Badcock DR. {{Visual search performance in the autism spectrum II: The radial frequency search task with additional segmentation cues}}. {Neuropsychologia};2010 (Dec);48(14):4117-4124.
The Embedded Figures Test (EFT) requires detecting a shape within a complex background and individuals with autism or high Autism-spectrum Quotient (AQ) scores are faster and more accurate on this task than controls. This research aimed to uncover the visual processes producing this difference. Previously we developed a search task using radial frequency (RF) patterns with controllable amounts of target/distracter overlap on which high AQ participants showed more efficient search than low AQ observers. The current study extended the design of this search task by adding two lines which traverse the display on random paths sometimes intersecting target/distracters, other times passing between them. As with the EFT, these lines segment and group the display in ways that are task irrelevant. We tested two new groups of observers and found that while RF search was slowed by the addition of segmenting lines for both groups, the high AQ group retained a consistent search advantage (reflected in a shallower gradient for reaction time as a function of set size) over the low AQ group. Further, the high AQ group were significantly faster and more accurate on the EFT compared to the low AQ group. That is, the results from the present RF search task demonstrate that segmentation and grouping created by intersecting lines does not further differentiate the groups and is therefore unlikely to be a critical factor underlying the EFT performance difference. However, once again, we found that superior EFT performance was associated with shallower gradients on the RF search task.
2. Asberg J. {{Patterns of language and discourse comprehension skills in school-aged children with autism spectrum disorders}}. {Scand J Psychol};2010 (Dec);51(6):534-539.
Asberg, J. (2010). Patterns of language and discourse comprehension skills in school-aged children with autism spectrum disorders. Scandinavian Journal of Psychology 51, 534-539. The present study examined patterns of language and discourse comprehension skills in Swedish school-aged children with autism spectrum disorders (ASD) (n = 16) as compared to a slightly younger group of typically developing children (n = 16) matched for non-verbal cognitive ability. Results suggested significantly lower abilities in narrative discourse comprehension for the ASD group, but not in oral receptive vocabulary or reception of grammar. This difficulty with discourse-level comprehension appeared to be of a general nature, as no evidence was found for the hypothesis that participants with ASD would find comprehension of inferential discourse information disproportionally more difficult than stated information, or for the hypothesis that discourse processing in ASD would be characterized by an elevated processing of explicitly stated narrative details. The study has clinical and educational implications, as the findings suggest that children with ASD would benefit from being offered specific support for discourse-level comprehension.
3. Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, Parner ET. {{Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders}}. {J Autism Dev Disord};2010 (Dec);40(12):1423-1430.
Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards regression. No association was found between any maternal infection and diagnosis of ASDs in the child when looking at the total period of pregnancy: adjusted hazard ratio = 1.14 (CI: 0.96-1.34). However, admission to hospital due to maternal viral infection in the first trimester and maternal bacterial infection in the second trimester were found to be associated with diagnosis of ASDs in the offspring, adjusted hazard ratio = 2.98 (CI: 1.29-7.15) and adjusted hazard ratio = 1.42 (CI: 1.08-1.87), respectively. Our results support prior hypotheses concerning early prenatal viral infection increasing the risk of ASDs.
4. Baruth JM, Casanova MF, El-Baz A, Horrell T, Mathai G, Sears L, Sokhadze E. {{Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Evoked-Gamma Frequency Oscillations in Autism Spectrum Disorder (ASD)}}. {J Neurother};2010 (Jul 1);14(3):179-194.
INTRODUCTION: It has been reported that individuals with Autism Spectrum Disorder (ASD) have abnormal reactions to the sensory environment and visuo-perceptual abnormalities. Electrophysiological research has provided evidence that gamma band activity (30-80 Hz) is a physiological indicator of the co-activation of cortical cells engaged in processing visual stimuli and integrating different features of a stimulus. A number of studies have found augmented and indiscriminative gamma band power at early stages of visual processing in ASD; this may be related to decreased inhibitory processing and an increase in the ratio of cortical excitation to inhibition. Low frequency or ‘slow’ (</=1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. METHODS: We wanted to test the hypothesis of gamma band abnormalities at early stages of visual processing in ASD by investigating relative evoked (i.e. ~ 100 ms) gamma power in 25 subjects with ASD and 20 age-matched controls using Kanizsa illusory figures. Additionally, we wanted to assess the effects of 12 sessions of bilateral ‘slow’ rTMS to the dorsolateral prefrontal cortex (DLPFC) on evoked gamma activity using a randomized controlled design. RESULTS: In individuals with ASD evoked gamma activity was not discriminative of stimulus type, whereas in controls early gamma power differences between target and non-target stimuli were highly significant. Following rTMS individuals with ASD showed significant improvement in discriminatory gamma activity between relevant and irrelevant visual stimuli. We also found significant improvement in the responses on behavioral questionnaires (i.e., irritability, repetitive behavior) as a result of rTMS. CONCLUSION: We proposed that ‘slow’ rTMS may have increased cortical inhibitory tone which improved discriminatory gamma activity at early stages of visual processing. rTMS has the potential to become an important therapeutic tool in ASD treatment and has shown significant benefits in treating core symptoms of ASD with few, if any side effects.
5. Bertone A, Hanck J, Kogan C, Chaudhuri A, Cornish K. {{Using perceptual signatures to define and dissociate condition-specific neural etiology: autism and fragile X syndrome as model conditions}}. {J Autism Dev Disord};2010 (Dec);40(12):1531-1540.
The functional link between genetic alteration and behavioral end-state is rarely straightforward and never linear. Cases where neurodevelopmental conditions defined by a distinct genetic etiology share behavioral phenotypes are exemplary, as is the case for autism and Fragile X Syndrome (FXS). In this paper and its companion paper, we propose a method for assessing the functional link between genotype and neural alteration across these target conditions by comparing their perceptual signatures. In the present paper, we discuss how such signatures can be used to (1) define and differentiate various aspects of neural functioning in autism and FXS, and subsequently, (2) to infer candidate causal (genetic) mechanisms based on such signatures (see companion paper, this issue).
6. Bertone A, Hanck J, Kogan C, Chaudhuri A, Cornish K. {{Associating neural alterations and genotype in autism and fragile x syndrome: incorporating perceptual phenotypes in causal modeling}}. {J Autism Dev Disord};2010 (Dec);40(12):1541-1548.
We have previously described (see companion paper, this issue) the utility of using perceptual signatures for defining and dissociating condition-specific neural functioning underlying early visual processes in autism and FXS. These perceptually-driven hypotheses are based on differential performance evidenced only at the earliest stages of visual information processing, mediated by local neural network functioning. In this paper, we first review how most large-scale neural models are unable to address atypical low-level perceptual functioning in autism, and then suggest how condition-specific, local neural endophenotypes (described in our companion paper) can be incorporated into causal models to infer target candidate gene or gene clusters that are implicated in autism’s pathogenesis. The usefulness of such a translational research approach is discussed.
7. Booth R, Happe F. {{« Hunting with a knife and … fork »: examining central coherence in autism, attention deficit/hyperactivity disorder, and typical development with a linguistic task}}. {J Exp Child Psychol};2010 (Dec);107(4):377-393.
A local processing bias, referred to as « weak central coherence, » has been postulated to underlie key aspects of autism spectrum disorder (ASD). Little research has examined whether individual differences in this cognitive style can be found in typical development, independent of intelligence, and how local processing relates to executive control. We present a brief and easy-to-administer test of coherence requiring global sentence completions. We report results from three studies assessing (a) 176 typically developing (TD) 8- to 25-year-olds, (b) individuals with ASD and matched controls, and (c) matched groups with ASD or attention deficit/hyperactivity disorder (ADHD). The results suggest that the Sentence Completion Task can reveal individual differences in cognitive style unrelated to IQ in typical development, that most (but not all) people with ASD show weak coherence on this task, and that performance is not related to inhibitory control. The Sentence Completion Task was found to be a useful test instrument, capable of tapping local processing bias in a range of populations.
8. Brendel C, Belakhov V, Werner H, Wegener E, Gartner J, Nudelman I, Baasov T, Huppke P. {{Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model}}. {J Mol Med};2010 (Dec 1)
Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2 ( R168X ) mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients.
9. Carmody DP, Lewis M. {{Regional white matter development in children with autism spectrum disorders}}. {Dev Psychobiol};2010 (Dec);52(8):755-763.
In this pilot study the severity of autism spectrum disorders (ASD) was associated with alterations in white matter development. Children with ASD and without ASD were assessed by magnetic resonance imaging (MRI) for their myelination development on a regional basis. Measures were obtained in medial frontal cortex, temporal poles, and temporo-parietal junction in both left and right hemispheres. Children with ASD showed myelination that was greater than expected for their age in both left and right medial frontal cortex and showed myelination that was less than expected in left temporo-parietal junction. The severity of ASD symptoms, as assessed by the Autism Diagnostic Observation Schedule-Generic, was associated more with left hemisphere alterations than right hemisphere. (c) 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 755-763, 2010.
10. Carter M, Nikkel S, Fernandez B, Marshall C, Noor A, Lionel A, Prasad A, Pinto D, Joseph-George A, Noakes C, Fairbrother-Davies C, Roberts W, Vincent J, Weksberg R, Scherer S. {{Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder}}. {Clin Genet};2010 (Oct 23)
Carter MT, Nikkel SM, Fernandez BA, Marshall CR, Noor A, Lionel AC, Prasad A, Pinto D, Joseph-George AM, Noakes C, Fairbrother-Davies C, Roberts W, Vincent J, Weksberg R, Scherer SW. Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder. We describe the identification and clinical presentation of four individuals from three unrelated families with hemizygous deletions involving the DPYD gene at chromosome 1p21.3. DPYD encodes dihydropyrimidine dehydrogenase, which is the initial and rate-limiting enzyme in the catabolism of pyrimidine bases. All four individuals described met diagnostic criteria for autism spectrum disorder with severe speech delay. Patient 1’s deletion was originally reported in 2008, and more detailed clinical information is provided. Subsequently, this male individual was found to have a missense mutation in the X-linked PTCHD1 autism susceptibility gene, which may also contribute to the phenotype. Patients 2 and 3 are siblings with a novel deletion encompassing the DPYD gene. In their mother, the genomic region deleted from chromosome 1p21.3 was inserted into chromosome 10. A fourth proband had a novel 10-kb intragenic deletion of exon 6 of the DPYD gene detected on a higher resolution microarray. Our study suggests that hemizygous deletions involving the DPYD locus present with variable phenotypes which can include speech delay and autistic features, and may also be influenced by additional mutations in other genes, issues which need to be considered in genetic counseling.
11. Coolican J, Smith IM, Bryson SE. {{Brief parent training in pivotal response treatment for preschoolers with autism}}. {J Child Psychol Psychiatry};2010 (Dec);51(12):1321-1330.
BACKGROUND: Evidence of improved outcomes with early behavioural intervention has placed the early treatment of autism as a health priority. However, long waiting lists for treatment often preclude timely access, raising the question of whether parents could be trained in the interim. Parent training in pivotal response treatment (PRT) has been shown to enhance the communication skills of children with autism. This is typically provided within a 25-hour programme, although less intensive parent training may also be effective. The main objective of the present study was to evaluate the efficacy of brief training in PRT for parents of preschoolers with autism, who were awaiting, or unable to access, more comprehensive treatment. METHOD: Eight preschoolers with autism and their parents participated in the study. A non-concurrent multiple (across-participants) baseline design was used, in which parents were seen individually for three 2-hour training sessions on PRT. Child and parent outcomes were assessed before, immediately after, and 2 to 4 months following training using standardised tests, questionnaires and behaviour coded directly from video recordings. RESULTS: Overall, children’s communication skills, namely functional utterances, increased following training. Parents’ fidelity in implementing PRT techniques also improved after training, and generally these changes were maintained at follow-up. A moderate to strong relationship was found between parents’ increased ability to implement PRT techniques and improvement in the children’s communication skills. CONCLUSION: Our findings suggest that brief parent training in PRT promises to provide an immediate, cost-effective intervention that could be adopted widely.
12. David N, Rose M, Schneider TR, Vogeley K, Engel AK. {{Brief report: altered horizontal binding of single dots to coherent motion in autism}}. {J Autism Dev Disord};2010 (Dec);40(12):1549-1551.
Individuals with autism often show a fragmented way of perceiving their environment, suggesting a disorder of information integration, possibly due to disrupted communication between brain areas. We investigated thirteen individuals with high-functioning autism (HFA) and thirteen healthy controls using the metastable motion quartet, a stimulus consisting of two dots alternately presented at four locations of a hypothetical square, thereby inducing an apparent motion percept. This percept is vertical or horizontal, the latter requiring binding of motion signals across cerebral hemispheres. Decreasing the horizontal distance between dots could facilitate horizontal percepts. We found evidence for altered horizontal binding in HFA: Individuals with HFA needed stronger facilitation to experience horizontal motion. These data are interpreted in light of reduced cross-hemispheric communication.
13. Ehninger D, Silva AJ. {{Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders}}. {Trends Mol Med};2010 (Nov 4)
Tuberous sclerosis (TSC) is a genetic disorder caused by heterozygous mutations in the TSC1 or TSC2 genes and is associated with autism spectrum disorders (ASD) in 20-60% of cases. In addition, altered TSC/mTOR signaling is emerging as a feature common to a subset of ASD. Recent findings, in animal models, show that restoration of the underlying molecular defect can improve neurological dysfunction in several of these models, even if treatment is initiated in adult animals, suggesting that pathophysiological processes in the mature brain contribute significantly to the overall neurological phenotype in these models. These findings suggest that windows for therapeutic intervention in ASD could be wider than thought previously.
14. Ekiel A, Aptekorz M, Kazek B, Wiechula B, Wilk I, Martirosian G. {{[Intestinal microflora of autistic children]}}. {Med Dosw Mikrobiol};2010;62(3):237-243.
Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea. These problems are often connected with deregulation of physiological microflora in intestine. The aim of this study was to determine differences in intestinal microflora of autistic and healthy children. Strains of Clostridium spp. and enterococci were isolated more frequently from stool samples of autistic children and rarely lactobacilli. Quantitative differences were observed maliny among staphylococci, Candida spp. and Clostridium perfringens. Monitoring and stabilization of intestinal microflora and knowledge about role of particular strains in etiology of autistic disorders can increase the chances for appropriate therapy.
15. Ghaziuddin N, Gih D, Barbosa V, Maixner DF, Ghaziuddin M. {{Onset of catatonia at puberty: electroconvulsive therapy response in two autistic adolescents}}. {J ECT};2010 (Dec);26(4):274-277.
Catatonia is a syndrome of motor and behavioral disturbance. It is a poorly understood condition, which is underrecognized and may go untreated despite intensive medical workup and numerous unsuccessful medication trials. However, with treatments known to be effective, such as benzodiazepines and/or electroconvulsive therapy, patients may return to their baseline functioning. Autism and catatonia have been previously reported together. We report 2 patients with autism and mental retardation who developed catatonic symptoms at the onset of puberty. Both patients experienced persistent symptoms over several years and presented with a history of motor disturbance, functional decline, and episodic aggression. Both patients were treated with electroconvulsive therapy resulting in a positive response and functional improvement. Catatonia may persist as a chronic condition, lasting over several months or years, if not recognized and treated.
16. Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. {{Mitochondrial dysfunction in autism}}. {JAMA};2010 (Dec 1);304(21):2389-2396.
CONTEXT: Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism. OBJECTIVE: To evaluate mitochondrial defects in children with autism. DESIGN, SETTING, AND PATIENTS: Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls. MAIN OUTCOME MEASURES: Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate. RESULTS: The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with autism (6 of 10) had complex I activity below control range values. Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls. These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol x [min x mg protein](-1) vs 2.3 [95% CI, 1.7-2.9] nmol x [min x mg protein](-1), respectively; P = .01). Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol x [min x mg of protein](-1) vs 0.16 [95% CI, 0.12-0.20] nmol x [min x mg protein](-1) by complex III; P = .02). Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10(-4)). Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01). CONCLUSION: In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.
17. Green SA, Ben-Sasson A. {{Anxiety disorders and sensory over-responsivity in children with autism spectrum disorders: is there a causal relationship?}}. {J Autism Dev Disord};2010 (Dec);40(12):1495-1504.
Anxiety disorders and sensory over-responsivity (SOR) are common in children with autism spectrum disorders (ASD), and there is evidence for an association between these two conditions. Currently, it is unclear what causal mechanisms may exist between SOR and anxiety. We propose three possible theories to explain the association between anxiety and SOR: (a) SOR is caused by anxiety; (b) Anxiety is caused by SOR; or (c) SOR and anxiety are causally unrelated but are associated through a common risk factor or diagnostic overlap. In this paper, we examine support for each theory in the existing anxiety, autism, and neuroscience literature, and discuss how each theory informs choice of interventions and implications for future studies.
18. Gutman SA, Raphael EI, Ceder LM, Khan A, Timp KM, Salvant S. {{The Effect of a motor-based, social skills intervention for adolescents with high-functioning autism: two single-subject design cases}}. {Occup Ther Int};2010 (Dec);17(4):188-197.
The purpose of this study was to assess the effect of a motor-based, social skills intervention for two adolescents with high-functioning autism (HFA) using single-subject design. A description of the intervention is provided as a first step in the manualization process. The intervention was provided as a 7-week after-school program, once weekly to the paired participants. Intervention consisted of role-play methods in which motor behaviours were linked with their cognitive and emotional meanings. Baseline, intervention and 3-month probe data collection periods were carried out and then compared using visual inspection of graphed data, paired t-tests and a three-standard-deviation-band approach. Both participants displayed a statistically significant increase in targeted social skills behaviours from baseline to intervention and maintained this level at a 3-month post-intervention probe. These single-subject design cases illustrate that motor-based, social skills interventions may be effective for adolescents with HFA and warrant further testing. Copyright (c) 2010 John Wiley & Sons, Ltd.
19. Hultman CM, Sandin S, Levine SZ, Lichtenstein P, Reichenberg A. {{Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies}}. {Mol Psychiatry};2010 (Nov 30)
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged >/=50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged </=29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.Molecular Psychiatry advance online publication, 30 November 2010; doi:10.1038/mp.2010.121.
20. Isler JR, Martien KM, Grieve PG, Stark RI, Herbert MR. {{Reduced functional connectivity in visual evoked potentials in children with autism spectrum disorder}}. {Clin Neurophysiol};2010 (Dec);121(12):2035-2043.
OBJECTIVE: An analysis of EEG synchrony between homologous early visual areas tested the hypothesis that interhemispheric functional connectivity during visual stimulation is reduced in children with autism compared to controls. METHODS: EEG power and coherence within and between two homologous regions of the occipital cortex were measured during long latency flash visual evoked potentials. Measures were compared between two groups of children (5.5-8.5years), one with autism spectrum disorders and the other with typical development. RESULTS: In and below the theta band, interhemispheric synchrony was reduced in autistic subjects compared to typical controls by as much as 50%. Above the theta band interhemispheric synchrony in autistic children became indistinguishable from what would occur for uncorrelated cortical activity. Interhemispheric synchrony in autistic subjects was decreased in spite of bilaterally increased power. Wavelet power showed autistic children had a more rapid initial response to stimulation, a slower recovery, and more modulation at longer latencies. CONCLUSIONS: Results suggest that the sensory cortices of autistic children are hypersensitive to stimulation with concurrent diminished functional connectivity between hemispheres. SIGNIFICANCE: Simultaneously increased intrahemispheric power and decreased interhemispheric synchronization of elementalvisual information suggests either that power increases cause poor interhemispheric connectivity or that processes, such as thalamocortical regulation, impact power and coherence independently.
21. James WH. {{A potential cause of the reported increase in rates of autism}}. {Int J Epidemiol};2010 (Dec);39(6):1676-1677.
22. Johnston K, Madden AK, Bramham J, Russell AJ. {{Response Inhibition in Adults with Autism Spectrum Disorder Compared to Attention Deficit/Hyperactivity Disorder}}. {J Autism Dev Disord};2010 (Nov 30)
Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are hypothesised to involve core deficits in executive function. Previous studies have found evidence of a double dissociation between the disorders on specific executive functions (planning and response inhibition). To date most research has been conducted with children. No studies have directly compared the stable cognitive profile of adults. It was hypothesised that adults with ASD would show generally intact response inhibition whereas those with ADHD would show more global impairment. Participants were 24 adults aged 18-55 with high functioning ASD, 24 with ADHD, and 14 age and IQ matched controls. Participants completed three standardised measures of response inhibition. Participants with ASD had generally intact response inhibition but slow response latencies, possibly due to deficits in response initiation. Adults with ADHD did not show the more global impairments hypothesised. There were some significant differences between the clinical groups across measures of inhibition. In terms of performance style, adults with ASD were slow and accurate whilst those with ADHD showed an impulsive style.
23. Joosten AV, Bundy AC. {{Sensory processing and stereotypical and repetitive behaviour in children with autism and intellectual disability}}. {Aust Occup Ther J};2010 (Dec);57(6):366-372.
Background: Sensory processing disorders have been linked to stereotypical behaviours in children with intellectual disability (ID) and autism spectrum disorders (ASD) and to anxiety in children with ASD. In earlier phases of this study with the same participants, we found that those with both ASD and ID were more motivated than those with ID alone to engage in stereotypical behaviour to alleviate anxiety. In this phase, we confirmed that children with both ASD and ID and those with ID alone process sensation differently than typically developing children. We asked: Do the sensory processing difficulties of children with ASD and ID differ significantly from those of children with ID alone in a way that would help explain the increased anxiety of the former group? Method: Parents of children with ASD and ID (n = 29; mean age 9.7 years) and with ID alone (n = 23; mean age 9.5 years) completed a Sensory Profile (SP) to provide information about their children’s sensory processing abilities. SP quadrant scores for each group were compared with each other and with the published norms of typically developing children. Results: Children with ASD and ID and with ID alone processed sensory information differently than typically developing children (P = 0.0001;d = > 2.00). Children with both ASD and ID were significantly more sensitive (P = 0.007;d = 0.70) and avoidant (P < 0.05;d = 0.47) than the children with ID alone. Conclusion: We conclude that increased sensitivity and the tendency to avoid sensation may help explain anxiety in children with autism.
24. Joshi G, Biederman J, Wozniak J, Doyle R, Hammerness P, Galdo M, Sullivan N, Williams C, Brethel K, Woodworth KY, Mick E. {{Response to Second Generation Antipsychotics in Youth with Comorbid Bipolar Disorder and Autism Spectrum Disorder}}. {CNS Neurosci Ther};2010 (Nov 29)
Objective: To assess the impact of comorbid autism spectrum disorders (ASD) on the response to second-generation antipsychotics (SGA) in pediatric bipolar disorder (BPD). Methods: Secondary analysis of identically designed 8-week open-label trials of SGA monotherapy (risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole) in youth with BPD. Results: Of the 151 BPD subjects 15% (n= 23) met criteria for comorbid ASD. There were no differences in the rate of antimanic response (YMRS change >/=30% or CGI-Improvement </=2: 65% vs. 69%; P= 0.7) in the presence of comorbid ASD. Conclusion: No difference observed in the rate of antimanic response or tolerability to SGA monotherapy in the presence of ASD comorbidity.
25. Kern JK, Geier DA, Adams JB, Geier MR. {{A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism spectrum disorder}}. {Biometals};2010 (Dec);23(6):1043-1051.
The study purpose was to compare the quantitative results from tests for urinary porphyrins, where some of these porphyrins are known biomarkers of heavy metal toxicity, to the independent assessments from a recognized quantitative measurement, the Autism Treatment Evaluation Checklist (ATEC), of specific domains of autistic disorders symptoms (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in a group of children having a clinical diagnosis of autism spectrum disorder (ASD). After a Childhood Autism Rating Scale (CARS) evaluation to assess the development of each child in this study and aid in confirming their classification, and an ATEC was completed by a parent, a urinary porphyrin profile sample was collected and sent out for blinded analysis. Urinary porphyrins from twenty-four children, 2-13 years of age, diagnosed with autism or PDD-NOS were compared to their ATEC scores as well as their scores in the specific domains (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) assessed by ATEC. Their urinary porphyrin samples were evaluated at Laboratoire Philippe Auguste (which is an ISO-approved clinical laboratory). The results of the study indicated that the participants’ overall ATEC scores and their scores on each of the ATEC subscales (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) were linearly related to urinary porphyrins associated with mercury toxicity. The results show an association between the apparent level of mercury toxicity as measured by recognized urinary porphyrin biomarkers of mercury toxicity and the magnitude of the specific hallmark features of autism as assessed by ATEC.
26. Koh HC, Milne E, Dobkins K. {{Contrast sensitivity for motion detection and direction discrimination in adolescents with autism spectrum disorders and their siblings}}. {Neuropsychologia};2010 (Dec);48(14):4046-4056.
The magnocellular (M) pathway hypothesis proposes that impaired visual motion perception observed in individuals with Autism Spectrum Disorders (ASD) might be mediated by atypical functioning of the subcortical M pathway, as this pathway provides the bulk of visual input to cortical motion detectors. To test this hypothesis, we measured luminance and chromatic contrast sensitivity, thought to tap M and Parvocellular (P) pathway processing, respectively. We also tested the hypothesis that motion processing is impaired in ASD using a novel paradigm that measures motion processing while controlling for detectabilty. Specifically, this paradigm compares contrast sensitivity for detection of a moving grating with contrast sensitivity for direction-of-motion discrimination of that same moving grating. Contrast sensitivities from adolescents with ASD were compared to typically-developing adolescents, and also unaffected siblings of individuals with ASD (SIBS). The results revealed significant group differences on P, but not M, pathway processing, with SIBS showing higher chromatic contrast sensitivity than both participants with ASD and TD participants. This atypicality, unique to SIBS, suggests the possible existence of a protective factor in these individuals against developing ASD. The results also revealed impairments in motion perception in both participants with ASD and SIBS, which may be an endophenotype of ASD. This impairment may be driven by impairments in motion detectors and/or by reduced input from neural areas that project to motion detectors, the latter possibility being consistent with the notion of reduced connectivity between neural areas in ASD.
27. Kumar RA. {{SHANK2 redemption: another synaptic protein for mental retardation and autism}}. {Clin Genet};2010 (Dec);78(6):519-521.
28. Lemonnier E, Ben-Ari Y. {{The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects}}. {Acta Paediatr};2010 (Dec);99(12):1885-1888.
The inhibitory transmitter GABA has been suggested to play an important role in infantile autistic syndrome (IAS), and extensive investigations suggest that excitatory actions of GABA in neurological disorders are because of a persistent increase of [Cl(-) ](I) . AIMS: To test the effects of the chloride co-transporter NKCC1 diuretic compound Bumetanide that reduces [Cl(-) ](I) on IAS. METHODS: Bumetanide was administered daily (1mg daily) during a 3-month period and clinical and biological tests made. We used 5 standard IAS severity tests – Childhood Autism Rating Scale, Aberrant Behaviour Checklist, Clinical Global Impressions; Repetitive and Restrictive Behaviour and the Regulation Disorder Evaluation Grid. RESULTS: We report a significant improvement in IAS with no side effects. CONCLUSION: Bumetanide decreases autistic behaviour with no side effects suggesting that diuretic agents may exert beneficial effects on IAS and that alterations of the actions of GABA may be efficient in IAS treatment calling for large scale randomized trials.
29. Mack H, Fullana MA, Russell AJ, Mataix-Cols D, Nakatani E, Heyman I. {{Obsessions and compulsions in children with Asperger’s syndrome or high-functioning autism: a case-control study}}. {Aust N Z J Psychiatry};2010 (Dec);44(12):1082-1088.
OBJECTIVE: To compare the clinical characteristics and symptom severity of children with obsessive disorder (OCD) plus autism spectrum disorders (ASD) with those of children with OCD plus Tourette’s syndrome (TS) or OCD alone. METHOD: Children with OCD and ASD (OCD/ASD) (n = 12, mean age = 14.33, range: 12-18) were compared to children with OCD and TS (OCD/TS) (n = 12, mean age = 13.92, range: 9-17) and children with OCD-alone (OCD) (n = 12, mean age = 12.92, range: 9-17) on measures of obsessive-compulsive (OC) symptom frequency, severity, interference and other clinical variables. RESULTS: Patients from the OCD/ASD group rated their OC symptoms as equally distressing, time consuming and contributing to a similar level of interference in functioning as patients in the OCD/TS and OCD groups. The types of symptoms were similar across groups but patients with OCD/TS reported greater frequency of ordering and arranging compulsions, and a trend towards more sexual obsessions. Patients with OCD/ASD reported more peer relationship problems compared with the other two groups. CONCLUSIONS: Children with ASD may experience a similar level of impairment from OC symptoms as children with TS plus OCD and children with OCD only. It is suggested that it is useful to establish both diagnoses given that obsessions and compulsions may respond to treatment, and their alleviation may improve functioning in children on the autism spectrum.
30. Mirenda P, Smith IM, Vaillancourt T, Georgiades S, Duku E, Szatmari P, Bryson S, Fombonne E, Roberts W, Volden J, Waddell C, Zwaigenbaum L. {{Validating the Repetitive Behavior Scale-revised in young children with autism spectrum disorder}}. {J Autism Dev Disord};2010 (Dec);40(12):1521-1530.
This study examined the factor structure of the Repetitive Behavior Scale-Revised (RBS-R) in a sample of 287 preschool-aged children with autism spectrum disorder (ASD). A confirmatory factor analysis was used to examine six competing structural models. Spearman’s rank order correlations were calculated to examine the associations between factor scores and variables of interest. The 3- and 5-factor models were selected as preferable on the basis of fit statistics and parsimony. For both models, the strongest correlations were with problem behavior scores on the Child Behavior Checklist and repetitive behavior scores on the ADI-R. Developmental index standard scores were not correlated with factors in either model. The results confirm the utility of the RBS-R as a measure of repetitive behaviors in young children with ASD.
31. Mukaddes NM, Herguner S, Tanidir C. {{Psychiatric disorders in individuals with high-functioning autism and Asperger’s disorder: Similarities and differences}}. {World J Biol Psychiatry};2010 (Dec);11(8):964-971.
Abstract Objectives. To investigate and compare the rate and type of psychiatric co-morbidity in individuals with diagnosis of high functioning autism (HFA) and Asperger’s disorder (AS). Methods. This study includes 30 children and adolescents with diagnosis of HFA and 30 with diagnosis of AS. Diagnoses of HFA and AS were made using strict DSM-IV criteria. Psychiatric co-morbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL-T). Results. The rate of comorbid psychiatric disorders was very high in both groups (93.3% in HFA and 100% in AS). The most common disorder in both groups was attention deficit hyperactivity disorder. There was no statistically significant difference between groups in the rate of associated psychiatric disorders, except for major depressive disorder (P = 0.029) and ADHD-combined type (P = 0.030). The AS group displayed greater comorbidity with depressive disorders and ADHD-CT. Conclusion. From a clinical perspective, it could be concluded that both disorders involve a high risk for developing psychiatric disorders, with AS patients at greater risk for depression. From a nosological perspective, the substantial similarities in terms of psychiatric comorbidity may support the idea that both disorders are on the same spectrum and differs in some aspects.
32. Norbury CF, Griffiths H, Nation K. {{Sound before meaning: Word learning in autistic disorders}}. {Neuropsychologia};2010 (Dec);48(14):4012-4019.
Successful word learning depends on the integration of phonological and semantic information with social cues provided by interlocutors. How then, do children with autism spectrum disorders (ASDs) learn new words when social impairments pervade? We recorded the eye-movements of verbally-able children with ASD and their typical peers while completing a word learning task in a social context. We assessed learning of semantic and phonological features immediately after learning and again four weeks later. Eye-movement data revealed that both groups could follow social cues, but that typically developing children were more sensitive to the social informativeness of gaze cues. In contrast, children with ASD were more successful than peers at mapping phonological forms to novel referents; however, this advantage was not maintained over time. Typical children showed clear consolidation of learning both semantic and phonological information, children with ASD did not. These results provide unique evidence of qualitative differences in word learning and consolidation and elucidate the different mechanisms underlying the unusual nature of autistic language.
33. Oosterling I, Visser J, Swinkels S, Rommelse N, Donders R, Woudenberg T, Roos S, van der Gaag RJ, Buitelaar J. {{Randomized controlled trial of the focus parent training for toddlers with autism: 1-year outcome}}. {J Autism Dev Disord};2010 (Dec);40(12):1447-1458.
This randomized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone. The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. (Eur Child Adolesc Psychiatr 11:266-272, 2002). Seventy-five toddlers with autism spectrum disorder (65 autism, 10 PDD-NOS, mean age = 34.4 months, SD = 6.2) were enrolled. Analyses were conducted on a final sample of 67 children (lost to follow-up = 8). No significant intervention effects were found for any of the primary (language), secondary (global clinical improvement), or mediating (child engagement, early precursors of social communication, or parental skills) outcome variables, suggesting that the ‘Focus parent training’ was not of additional value to the more general care-as-usual.
34. Pisula E, Kossakowska Z. {{Sense of coherence and coping with stress among mothers and fathers of children with autism}}. {J Autism Dev Disord};2010 (Dec);40(12):1485-1494.
The purpose of the study was to compare the level of sense of coherence (SOC) in parents of children with autism and in parents of typically developing children, and to examine the association between SOC level and coping strategies. Two questionnaires were used: Sense of Coherence Scale (SOC-29) and Ways of Coping Questionnaire. Parents of children with autism had a lower level of the total SOC, meaningfulness, and manageability compared with controls, and used escape-avoidance coping more often. No differences in SOC level were found between mothers and fathers. In parents of children with autism the SOC level was positively associated with seeking social support and self-controlling, and negatively with accepting responsibility and positive reappraisal.
35. Roy M, Balaratnasingam S. {{Missed diagnosis of autism in an Australian Indigenous psychiatric population}}. {Australas Psychiatry};2010 (Dec);18(6):534-537.
Objective: The aim of this paper is to review the diagnosis among adult Indigenous patients from the Kimberley region of Western Australia who had an existing diagnosis of schizophrenia. A visit from a psychiatrist specializing in intellectual disability provided the opportunity for conducting psychiatric assessments from a developmental perspective. Method: Selected patients with schizophrenia were assessed from an intellectual disability perspective from an active case load of 215 patients. Result: Thirteen out of 14 selected patients were considered to have a diagnosis of autism when a developmental history was undertaken. Case studies are presented to illustrate the overlap in symptoms and potential for the diagnosis of autism to be missed. Conclusions: Autism spectrum disorders may be missed in Indigenous population groups. This has implications for treatment and service provision. Clinicians need to be mindful of the diagnostic possibility that an autism spectrum disorder might be masquerading as schizophrenia in the context of intellectual disability and atypical presentation.
36. Ruble LA, McGrew J, Dalrymple N, Jung LA. {{Examining the quality of IEPs for young children with autism}}. {J Autism Dev Disord};2010 (Dec);40(12):1459-1470.
The purpose of this study was to develop an Individual Education Program (IEP) evaluation tool based on Individuals with Disabilities Education Act (IDEA) requirements and National Research Council recommendations for children with autism; determine the tool’s reliability; test the tool on a pilot sample of IEPs of young children; and examine associations between IEP quality and school, teacher, and child characteristics. IEPs for 35 students with autism (Mage = 6.1 years; SD = 1.6) from 35 different classrooms were examined. The IEP tool had adequate interrater reliability (ICC = .70). Results identified no statistically significant association between demographics and IEP quality, and IEPs contained relatively clear descriptions of present levels of performance. Weaknesses of IEPs were described and recommendations provided.
37. Ryan C, Charragain CN. {{Teaching emotion recognition skills to children with autism}}. {J Autism Dev Disord};2010 (Dec);40(12):1505-1511.
Autism is associated with difficulty interacting with others and an impaired ability to recognize facial expressions of emotion. Previous teaching programmes have not addressed weak central coherence. Emotion recognition training focused on components of facial expressions. The training was administered in small groups ranging from 4 to 7 children. Improvements were significantly better for the training group (n = 20, mean age 9 years, 3 months) than a waiting list control group (n = 10, mean age 10 years, 7 months). Pre and post measures revealed an effect size of the training of Cohen’s d = 1.42. The impact of the training was highly significant. There was evidence of some generalisation of the emotion recognition and improvements at follow-up.
38. Shukla DK, Keehn B, Lincoln AJ, Muller RA. {{White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study}}. {J Am Acad Child Adolesc Psychiatry};2010 (Dec);49(12):1269-1278 e1262.
OBJECTIVE: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children. METHOD: DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, the genu, body, and splenium of the corpus callosum, the genu and anterior and posterior limbs of the internal capsule, and the middle cerebellar peduncle. RESULTS: Children with ASD had reduced FA and increased radial diffusion for whole-brain white matter and all three segments of the corpus callosum and internal capsule, compared with those in TD children. Increased MD was found for the whole brain and for anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for the middle cerebellar peduncle. CONCLUSIONS: Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for the internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.
39. Taylor JL, Seltzer MM. {{Changes in the autism behavioral phenotype during the transition to adulthood}}. {J Autism Dev Disord};2010 (Dec);40(12):1431-1446.
We examined whether exiting high school was associated with alterations in rates of change in autism symptoms and maladaptive behaviors. Participants were 242 youth with ASD who had recently exited the school system and were part of our larger longitudinal study; data were collected at five time points over nearly 10 years. Results indicated overall improvement of autism symptoms and internalized behaviors over the study period, but slowing rates of improvement after exit. Youth who did not have an intellectual disability evidenced the greatest slowing in improvement. Lower family income was associated with less improvement. Our findings suggest that adult day activities may not be as intellectually stimulating as educational activities in school, reflected by less phenotypic improvement after exit.
40. Villagonzalo KA, Dodd S, Dean O, Gray K, Tonge B, Berk M. {{Oxidative pathways as a drug target for the treatment of autism}}. {Expert Opin Ther Targets};2010 (Dec);14(12):1301-1310.
IMPORTANCE OF THE FIELD: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed. AREAS COVERED IN THIS REVIEW: Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews. WHAT THE READER WILL GAIN: This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder. TAKE HOME MESSAGE: Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.
41. Wallace KS, Rogers SJ. {{Intervening in infancy: implications for autism spectrum disorders}}. {J Child Psychol Psychiatry};2010 (Dec);51(12):1300-1320.
There is a scarcity of empirically validated treatments for infants and toddlers under age 3 years with autism spectrum disorders (ASD), as well as a scarcity of empirical investigation into successful intervention characteristics for this population. Yet early screening efforts are focused on identifying autism risk in children under age 3 years. In order to build ASD interventions for infants and toddlers upon a foundation of evidence-based characteristics, the current paper presents the results of a systematic literature search and effect size analysis of efficacious interventions for infants and toddlers with other developmental disorders: those who were born prematurely, have developmental impairments, or are at high risk for developmental impairments due to the presence of a biological or familial condition associated with developmental impairments. A review of 32 controlled, high-quality experimental studies revealed that the most efficacious interventions routinely used a combination of four specific intervention procedures, including (1) parent involvement in intervention, including ongoing parent coaching that focused both on parental responsivity and sensitivity to child cues and on teaching families to provide the infant interventions, (2) individualization to each infant’s developmental profile, (3) focusing on a broad rather than a narrow range of learning targets, and (4) temporal characteristics involving beginning as early as the risk is detected and providing greater intensity and duration of the intervention. These four characteristics of efficacious interventions for infants and toddlers with other developmental challenges likely represent a solid foundation from which researchers and clinicians can build efficacious interventions for infants and toddlers at risk for or affected by ASD.
42. Wilson CE, Brock J, Palermo R. {{Attention to social stimuli and facial identity recognition skills in autism spectrum disorder}}. {J Intellect Disabil Res};2010 (Dec);54(12):1104-1115.
Background Previous research suggests that individuals with autism spectrum disorder (ASD) have a reduced preference for viewing social stimuli in the environment and impaired facial identity recognition. Methods Here, we directly tested a link between these two phenomena in 13 ASD children and 13 age-matched typically developing (TD) controls. Eye movements were recorded while participants passively viewed visual scenes containing people and objects. Participants also completed independent matching tasks for faces and objects. Results and Conclusions Behavioural data showed that participants with ASD were impaired on both face- and object-matching tasks relative to TD controls. Eye-tracking data revealed that both groups showed a strong bias to orient towards people. TD children spent proportionally more time looking at people than objects; however, there was no difference in viewing times between people and objects in the ASD group. In the ASD group, an individual’s preference for looking first at the people in scenes was associated with level of face recognition ability. Further research is required to determine whether a causal relationship exists between these factors.
43. Wong YM. {{Tongue Acupuncture and Autism Spectrum Disorder}}. {J Altern Complement Med};2010 (Nov 29)
