1. Barneveld PS, Pieterse J, de Sonneville L, van Rijn S, Lahuis B, van Engeland H, Swaab H. {{Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders}}. {Schizophr Res} (Oct 6)
This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.
2. Calhoun M, Longworth M, Chester VL. {{Gait patterns in children with autism}}. {Clin Biomech (Bristol, Avon)} (Oct 7)
BACKGROUND: Very few studies have examined the gait patterns of children with autism. A greater awareness of movement deviations could be beneficial for treatment planning. The purpose of this study was to compare kinematic and kinetic gait patterns in children with autism versus age-matched controls. METHODS: Twelve children with autism and twenty-two age-matched controls participated in the study. An eight camera motion capture system and four force plates were used to compute joint angles and joint kinetics during walking. Parametric analyses and principal component analyses were applied to kinematic and kinetic waveform variables from the autism (n=12) and control (n=22) groups. Group differences in parameterization values and principal component scores were tested using one-way ANOVAs and Kruskal-Wallis tests. FINDINGS: Significant differences between the autism and control group were found for cadence, and peak hip and ankle kinematics and kinetics. Significant differences were found for three of the principal component scores: sagittal ankle moment principal component one, sagittal ankle angle principal component one, and sagittal hip moment principal component two. Results suggest that children with autism demonstrate reduced plantarflexor moments and increased dorsiflexion angles, which may be associated with hypotonia. Decreased hip extensor moments were found for the autism group compared to the control group, however, the clinical significance of this result is unclear. INTERPRETATION: This study has identified several gait variables that were significantly different between autism and control group walkers. This is the first study to provide a comprehensive analysis of gait patterns in children with autism.
3. Colak D, Al-Dhalaan H, Nester M, Albakheet A, Al-Younes B, Al-Hassnan Z, Al-Dosari M, Chedrawi A, Al-Owain M, Abudheim N, Al-Alwan L, Al-Odaib A, Ozand P, Inan MS, Kaya N. {{Genomic and transcriptomic analyses distinguish classic Rett and Rett-like syndrome and reveals shared altered pathways}}. {Genomics} (Oct 7)
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by derangements in nervous system especially in cognition and behavior. The present study aims to understand the molecular underpinnings of two subtypes of RTT, classic RTT and Rett-like, and to elucidate common pathways giving rise to common RTT phenotype using genomic and transcriptomic approaches. Mutation screening on selected nuclear genes revealed only MECP2 mutations in a subset of classic RTT patients. MLPA assays and mtDNA screenings were all negative. Genome-wide copy number analysis indicated a novel duplication on X chromosome. Transcriptional profiling revealed blood gene signatures that clearly distinguish classic RTT and RTT-like patients, as well as shared altered pathways in interleukin-4 and NF-kappaB signaling pathways in both subtypes of the syndrome. To our knowledge, this is the first report on investigating common regulatory mechanisms/signaling pathways that may be relevant to the pathobiology of the « common RTT » phenotype.
4. Dissanayake C, Shembrey J, Suddendorf T. {{Delayed video self-recognition in children with high functioning autism and Asperger’s disorder}}. {Autism} (Sep);14(5):495-508.
Two studies are reported which investigate delayed video self-recognition (DSR) in children with autistic disorder and Asperger’s disorder relative to one another and to their typically developing peers. A secondary aim was to establish whether DSR ability is dependent on metarepresentational ability. Children’s verbal and affective responses to their image were also measured. Three groups of male children between 5 and 9 years, comprising 15 with high-functioning autistic disorder (HFA), 12 with Asperger’s disorder (AspD), and 15 typically developing (TD) children, participated in Study 1. Study 2 included two groups of younger children (18 HFA; 18 TD) aged 4 to 7 years. Participant groups in each study were equally able to recognize themselves using delayed video feedback, and responded to their marked image with positive affect. This was so even amongst children with HFA who were impaired in their performance on false belief tasks, casting doubt on a metarepresentational basis of DSR.
5. Fukumoto A, Hashimoto T, Mori K, Tsuda Y, Arisawa K, Kagami S. {{Head circumference and body growth in autism spectrum disorders}}. {Brain Dev} (Oct 8)
Research has shown that there is a relationship between increased head circumference and autism spectrum disorders (ASD). This study examined this relationship during the first year of life in subjects with ASD. We compared 280 children with ASD and 609 controls. In the ASD-male group, increases were observed in head circumference from 3 to 12months, in height from 3 to 9months, and in body weight from 3 to 6 and 12months. On the other hand, in the ASD-female group increases in head circumference, in body height, and in body weight were only observed at 3months. After adjusting for height, weight, and age, only the head circumference in the male ASD group was significantly increased from 6 to 9months after birth, reaching a peak at 6months after birth. No difference was found in the female ASD group. Although body overgrowth in the ASD group also started early after birth, the increase in head circumference was more marked than that in body growth. The values of physical measurements in the first year may be useful, minimally invasive parameters for the early detection of autism in combination with observing the timing of certain behaviors such as smiling, eye contact, crawling, pointing, and joint attention.
6. Ghanizadeh A. {{Transplantation of GABAergic cell line as a novel hypothesized treatment for autism}}. {Epilepsy Behav} (Oct 8)
7. Hobson RP. {{Explaining autism: Ten reasons to focus on the developing self}}. {Autism} (Sep);14(5):391-407.
My aim in this paper is to present reasons for adopting a focus on the development of self/other-awareness when characterizing the developmental psychopathology of autism. The strengths of such a position include an emphasis on children’s emotional relations with embodied persons as foundational for their growing understanding of minds. I give special attention to the process of identifying with the attitudes of others, and experience of other-person-centred emotions, for the development of communication and thinking. The study of limitations in these aspects of self-other relatedness among individuals with autism is pivotal for understanding the pathogenesis of the syndrome.
8. Kamp-Becker I, Schroder J, Remschmidt H, Bachmann CJ. {{Health-related quality of life in adolescents and young adults with high functioning autism-spectrum disorder}}. {Psychosoc Med};7
Aim: Over the last years, health-related quality of life (HRQOL) has emerged as an important measure not only in somatic medicine but also in psychiatry. To date, there are only few reports on HRQOL in patients with autism-spectrum disorder (ASD). This study aimed at studying HRQOL in ASD patients with an IQ >70, using a self-report HRQOL questionnaire with cross-cultural validity.Methods: In this cross-sectional study, twenty-six male adolescents and young adults with the diagnosis of Asperger Syndrome, high functioning autism and atypical autism were evaluated, using the German version of the WHOQOL-BREF HRQOL questionnaire.Results: Mean WHOQOL-BREF global scores were 60.6 (SD +/-26.1), mean WHOQOL-BREF subscale scores were 70.1 (SD +/-19.1) for the domain « physical health », 61.5 (SD +/-21.9) for the domain « psychological health », 53.8 (SD +/-23.5) for the domain « social relationships » and 67.9 (SD +/-17.4) for the domain « environment ». Compared to a reference population of healthy controls, our sample scored significantly lower in three of four WHOQOL-BREF domains. In comparison to a reference sample of individuals with schizophrenia spectrum disorder (SSD), HRQOL of our sample was significantly better in all domains except for the « social relations » domain. There was a significant association between HRQOL and the Vineland Adaptive Behavior Scales domain « daily living skills », but not with age, IQ, or ADOS-G summary scores.Conclusion: Overall self-reported HRQOL in patients with high functioning ASD seems to be lower than in healthy individuals, but better than in patients with SSD. Also, higher HRQOL was associated with better daily living skills. This interrelationship should especially be accounted for in the design and application of treatment programmes for individuals with ASD, as it is of importance for the level of self-perceived HRQOL.
9. Keita L, Mottron L, Bertone A. {{Far visual acuity is unremarkable in autism: Do we need to focus on crowding?}}. {Autism Res} (Oct 6)
Although autism presents a unique perceptual phenotype defined in part by atypical (often enhanced) analysis of spatial information, few biologically plausible hypotheses have been advanced to explain its neural underpinnings. One plausible explanation is functional but altered lateral connectivity mediating early or local mechanisms selectively responsive to different stimulus attributes, including spatial frequency and contrast. The goal of the present study was first to assess far visual acuity in autism using Landolt-C optotypes defined by different local stimulus attributes. Second, we investigated whether acuity is differentially affected in autism when target optotypes are simultaneously presented with flanking stimuli at different distances. This typical detrimental « crowding effect » of flanking stimuli on target optotype discrimination is attributed to lateral inhibitory interaction of neurons encoding for visual properties of distracters close to the target. Results failed to demonstrate a between-group difference in acuity to Landolt-C optotypes, whether defined by luminance- or texture-contrast. However, the expected crowding effect at one gap-size opening distance was evidenced for the control group only; a small effect was observed for the autism group at two gap-size opening. These results suggest that although far visual acuity is unremarkable in autism, altered local lateral connectivity within early perceptual areas underlying spatial information processing in autism is atypical. Altered local lateral connectivity in autism might originate from an imbalance in excitatory/inhibitory neural signaling, resulting in changes regarding elementary feature extraction and subsequent downstream visual integration and visuo-spatial analysis. This notion is discussed within the context of characteristic lower- and higher-level perceptual processing in autism.
10. Key B. {{Using zebrafish to understand the neurodevelopment role of susceptibility genes for autism spectrum disorder}}. {Dev Biol} (Aug 1);344(1):526-527.
11. Kim Y, Cho SC, Shin MS, Kim JW, Lee SH, Kim BN. {{Retrospective case series of aripiprazole augmentation in pervasive developmental disorders}}. {Psychiatry Investig} (Sep);7(3):220-223.
Due to co-morbidities and treatment resistant nature of pervasive developmental disorder (PDD), diverse combinations of regimens have been tried. This retrospective study aimed to explore adjunctive use of aripiprazole in children with PDD. Changes in illness severity were measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) in 14 aripiprazole-treated patients with PDD. Improvement of illness severity was observed after aripiprazole add-on (5.8+/-0.8 to 4.9+/-1.0, Z=-2.75, p=0.001). Mean dosage was 7.7 mg/day [standard deviation (SD) 3.3, range 5-15]. A higher mean dosage was observed in group with improvement in symptoms (t=-2.33, df =12, p=0.004). The target symptoms most effectively improved after using aripiprazole were positive psychotic symptoms (mean CGI-I: 2.0+/-1.4, 3 responders/4 patients, 75% response) followed by aggressive behavior (2.5+/-1.7, 3/4, 75%), self-injurious behavior (2.0+/-1.0, 2/3, 67%), stereotypic behavior (2.7+/-1.2, 2/3, 67%), tic (2.8+/-1.0, 2/4, 50%), irritability (3.5+/-2.1, 1/2, 50%), obsessive behavior (2.5+/-2.1, 1/3, 33%), hyperactivity (3.4+/-1.6, 3/7, 43%) and mood fluctuation (3, 0/1, no response). Five patients (35%) discontinued aripiprazole due to treatment-emergent adverse effects (akathisia, insomnia, withdrawal). The results of this study suggest that aripiprazole augmentation may be used safely in maladaptive behaviors of some populations of PDD. However, future studies are required to confirm these preliminary findings.
12. Lemmon ME, Gregas M, Jeste SS. {{Risperidone Use in Autism Spectrum Disorders: A Retrospective Review of a Clinic-Referred Patient Population}}. {J Child Neurol} (Oct 6)
Risperidone is widely used in children with autism spectrum disorders for behavioral modification. In this study, the authors aimed to (1) describe a clinic-referred sample of patients with an autism spectrum disorder on risperidone, (2) identify differences between the success and nonsuccess groups, and (3) describe our experience with young children (< age 5 years) on risperidone. Eighty patients were initiated on risperidone. Indications included aggression (66%), impulsivity (14%), and stereotypies (4%). Sixty-six percent met criteria for success at 6 months and 53% at 1 year. Sixty-seven percent of the nonsuccess group reported side effects, compared to 47% of the success group. Weight gain was the most common side effect in both groups, followed by somnolence. Somnolence was the most robust predictor of nonsuccess. In our clinic-referred sample, the short-term success rate of risperidone was more than 50%, and side effects limited its use. Although weight gain was common, somnolence more significantly influenced treatment discontinuation.
13. Lombardo MV, Baron-Cohen S. {{The role of the self in mindblindness in autism}}. {Conscious Cogn} (Oct 5)
Since its inception the ‘mindblindness’ theory of autism has greatly furthered our understanding of the core social-communication impairments in autism spectrum conditions (ASC). However, one of the more subtle issues within the theory that needs to be elaborated is the role of the ‘self’. In this article, we expand on mindblindness in ASC by addressing topics related to the self and its central role in the social world and then review recent research in ASC that has yielded important insights by contrasting processes relating to both self and other. We suggest that new discoveries lie ahead in understanding how self and other are interrelated and/or distinct, and how understanding atypical self-referential and social-cognitive mechanisms may lead to novel ideas as to how to facilitate social-communicative abilities in ASC.
14. Mundy P, Gwaltney M, Henderson H. {{Self-referenced processing, neurodevelopment and joint attention in autism}}. {Autism} (Sep);14(5):408-429.
This article describes a parallel and distributed processing model (PDPM) of joint attention, self-referenced processing and autism. According to this model, autism involves early impairments in the capacity for rapid, integrated processing of self-referenced (proprioceptive and interoceptive) and other-referenced (exteroceptive) information. Measures of joint attention have proven useful in research on autism because they are sensitive to the early development of the ‘parallel’ and integrated processing of self- and other-referenced stimuli. Moreover, joint attention behaviors are a consequence, but also an organizer of the functional development of a distal distributed cortical system involving anterior networks including the prefrontal and insula cortices, as well as posterior neural networks including the temporal and parietal cortices. Measures of joint attention provide early behavioral indicators of atypical development in this parallel and distributed processing system in autism. In addition it is proposed that an early, chronic disturbance in the capacity for integrating self- and other-referenced information may have cascading effects on the development of self awareness in autism. The assumptions, empirical support and future research implications of this model are discussed.
15. Wallace GL, Dankner N, Kenworthy L, Giedd JN, Martin A. {{Age-related temporal and parietal cortical thinning in autism spectrum disorders}}. {Brain} (Oct 5)
Studies of head size and brain volume in autism spectrum disorders have suggested that early cortical overgrowth may be followed by prematurely arrested growth. However, the few investigations quantifying cortical thickness have yielded inconsistent results, probably due to variable ages and/or small sample sizes. We assessed differences in cortical thickness between high-functioning adolescent and young adult males with autism spectrum disorders (n = 41) and matched typically developing males (n = 40). We hypothesized thinner cortex, particularly in frontal, parietal and temporal regions, for individuals with autism spectrum disorders in comparison with typically developing controls. Furthermore, we expected to find an age x diagnosis interaction: with increasing age, more pronounced cortical thinning would be observed in autism spectrum disorders than typically developing participants. T(1)-weighted magnetization prepared rapid gradient echo 3 T magnetic resonance imaging scans were acquired from high-functioning males with autism spectrum disorders and from typically developing males matched group-wise on age (range 12-24 years), intelligence quotient (>/=85) and handedness. Both gyral-level and vertex-based analyses revealed significantly thinner cortex in the autism spectrum disorders group that was located predominantly in left temporal and parietal regions (i.e. the superior temporal sulcus, inferior temporal, postcentral/superior parietal and supramarginal gyri). These findings remained largely unchanged after controlling for intelligence quotient and after accounting for psychotropic medication usage and comorbid psychopathology. Furthermore, a significant age x diagnosis interaction was found in the left fusiform/inferior temporal cortex: participants with autism spectrum disorders had thinner cortex in this region with increasing age to a greater degree than did typically developing participants. Follow-up within group comparisons revealed significant age-related thinning in the autism spectrum disorders group but not in the typically developing group. Both thinner temporal and parietal cortices during adolescence and young adulthood and discrepantly accelerated age-related cortical thinning in autism spectrum disorders suggest that a second period of abnormal cortical growth (i.e. greater thinning) may be characteristic of these disorders.
16. Waltereit R, Japs B, Schneider M, de Vries PJ, Bartsch D. {{Epilepsy and Tsc2 Haploinsufficiency Lead to Autistic-Like Social Deficit Behaviors in Rats}}. {Behav Genet} (Oct 7)
There is a strong association between autism spectrum disorders (ASD), epilepsy and intellectual disability in humans, but the nature of these correlations is unclear. The monogenic disorder Tuberous Sclerosis Complex (TSC) has high rates of ASD, epilepsy and cognitive deficits. Here we used the Tsc2 (+/-) (Eker) rat model of TSC and an experimental epilepsy paradigm to study the causal effect of seizures on learning and memory and social behavior phenotypes. Status epilepticus was induced by kainic acid injection at P7 and P14 in wild-type and Tsc2 (+/-) rats. At the age of 3-6 months, adult rats were assessed in the open field, light/dark box, fear conditioning, Morris water maze, novel object recognition and social interaction tasks. Learning and memory was unimpaired in naive Tsc2 (+/-) rats, and experimental epilepsy did not impair any aspects of learning and memory in either wild-type or Tsc2 (+/-) rats. In contrast, rearing in the open field, novel object exploration and social exploration was reduced in naive Tsc2 (+/-) rats. Seizures induced anxiety and social evade, and reduced social exploration and social contact behavior in wild-type and Tsc2 (+/-) rats. Our study shows that Tsc2 haploinsufficiency and developmental status epilepticus in wild-type and Tsc2 (+/-) rats independently lead to autistic-like social deficit behaviors. The results suggest that the gene mutation may be sufficient to lead to some social deficits, and that seizures have a direct and additive effect to increase the likelihood and range of autistic-like behaviors.
17. Williams D. {{Theory of own mind in autism: Evidence of a specific deficit in self-awareness?}}. {Autism} (Sep);14(5):474-494.
Assuming that self-awareness is not a unitary phenomenon, and that one can be aware of different aspects of self at any one time, it follows that selective impairments in self-awareness can occur. This article explores the idea that autism involves a particular deficit in awareness of the ‘psychological self’, or ‘theory of own mind’. This hypothesised deficit renders individuals with autism spectrum disorder (ASD) at least as impaired at recognising their own mental states as at recognising mental states in other people. This deficit, it is argued, stands in contrast to an apparently typical awareness of the ‘physical self’ amongst people with autism. Theoretical implications of the empirical evidence are discussed.
18. Yang M, Perry K, Weber MD, Katz AM, Crawley JN. {{Social peers rescue autism-relevant sociability deficits in adolescent mice}}. {Autism Res} (Oct 6)
Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming in BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions.
19. Zwickel J, White SJ, Coniston D, Senju A, Frith U. {{Exploring the building blocks of social cognition: spontaneous agency perception and visual perspective taking in autism}}. {Soc Cogn Affect Neurosci} (Oct 7)
Individuals with autism spectrum disorders have highly characteristic impairments in social interaction and this is true also for those with high functioning autism or Asperger syndrome (AS). These social cognitive impairments are far from global and it seems likely that some of the building blocks of social cognition are intact. In our first experiment, we investigated whether high functioning adults who also had a diagnosis of AS would be similar to control participants in terms of their eye movements when watching animated triangles in short movies that normally evoke mentalizing. They were. Our second experiment using the same movies, tested whether both groups would spontaneously adopt the visuo-spatial perspective of a triangle protagonist. They did. At the same time autistic participants differed in their verbal accounts of the story line underlying the movies, confirming their specific difficulties in on-line mentalizing. In spite of this difficulty, two basic building blocks of social cognition appear to be intact: spontaneous agency perception and spontaneous visual perspective taking.
