1. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu S, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI, Jr., Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, Hallmayer J. {{A genomewide scan for common alleles affecting risk for autism}}. {Hum Mol Genet} (Jul 27)
While autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1,558 rigorously defined ASD families for one million single nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P<5×10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner’s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P<5×10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2, and TAF1C.
2. Benson PR, Daley D, Karlof KL, Robison D. {{Assessing expressed emotion in mothers of children with autism: The Autism-Specific Five Minute Speech Sample}}. {Autism} (Jul 29)
Background: Expressed emotion (EE) is a measure of family emotional climate found to be predictive of symptom levels in a range of psychiatric, medical, and developmental disorders, including autism. Method: Employing data from 104 mothers of children with autism, this study examines the Autism-Specific Five Minute Speech Sample (AFMSS), a modified EE coding system based on the widely used Five Minute Speech Sample (Magana et al., 1986). Findings: With the exception of one EE component, emotional over-involvement, the revised coding system demonstrated adequate internal consistency and good to excellent inter-rater and code-recode reliability. It also demonstrated acceptable validity, based on its significant correlations with factors linked to EE in previous research. Regression analyses also indicated AFMSS-EE to be a significant predictor of child social competence, but not child problem behaviors. Discussion: While further testing is required, the AFMSS appears to be a useful method of assessing EE within the context of parenting children with autism and related disorders.
3. Correia CT, Coutinho AM, Sequeira AF, Sousa IG, Venda LL, Almeida JP, Abreu RL, Lobo C, Miguel TS, Conroy J, Cochrane L, Gallagher L, Gill M, Ennis S, Oliveira GG, Vicente AM. {{Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TRKB signaling in autism}}. {Genes Brain Behav} (Jul 16)
The Brain Derived Neurotrophic Factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study BDNF levels in platelet rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, were examined. We found that BDNF levels in autistic children (N=146) were significantly higher (t=6.82; P<0.0001) than in control children (N=50) and were positively correlated with platelet serotonin distribution (r=0.22; P=0.004). BDNF heritability was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six SNPs (0.004 (Z((1df))=2.85)<P<0.039(Z((1df))=2.06)) and multiple haplotypes (5×10(-4) (chi((3df))=17.77)< P<0.042(chi((9df))=17.450)) in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however reflect a trend towards association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase of BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/TrkB signalling contribute to an increased vulnerability to autism.
4. Gogolla N, Leblanc JJ, Quast KB, Sudhof T, Fagiolini M, Hensch TK. {{Common circuit defect of excitatory-inhibitory balance in mouse models of autism}}. {J Neurodev Disord};2009 (Jun 1);1(2):172-181.
PURPOSE: One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement [1], are disrupted across heterogeneous ASD mouse models. METHODS: We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). RESULTS: PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). CONCLUSIONS: ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development, potential prevention and treatment of autism.
5. 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} (Jul 29)
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.
6. Lind S. {{Memory and the self in autism: A review and theoretical framework}}. {Autism} (Jul 29)
This article reviews research on (a) autobiographical episodic and semantic memory, (b) the self-reference effect, (c) memory for the actions of self versus other (the self-enactment effect), and (d) non-autobiographical episodic memory in autism spectrum disorder (ASD), and provides a theoretical framework to account for the bi-directional relationship between memory and the self in ASD. It is argued that individuals with ASD have diminished psychological self-knowledge (as a consequence of diagnostic social and communication impairments), alongside intact physical self-knowledge, resulting in an under-elaborated self-concept. Consequently, individuals with ASD show impaired autobiographical episodic memory and a reduced self-reference effect (which may each rely on psychological aspects of the self-concept) but do not show specific impairments in memory for their own rather than others’ actions (which may rely on physical aspects of the self-concept). However, it is also argued that memory impairments in ASD (e.g., in non-autobiographical episodic memory) may not be entirely accounted for in terms of self-related processes. Other factors, such as deficits in memory binding, may also play a role. Finally, it is argued that deficits in autobiographical episodic memory and future thinking may result in a diminished temporally extended self-concept in ASD.
