1. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. {{Promoting social behavior with oxytocin in high-functioning autism spectrum disorders}}. {Proc Natl Acad Sci U S A} (Feb 16)
Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients’ gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.
2. El-Fishawy P, State MW. {{The Genetics of Autism: Key Issues, Recent Findings, and Clinical Implications}}. {Psychiatr Clin North Am} (Mar);33(1):83-105.
Autism spectrum disorders (ASDs) are highly heritable. Gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding opportunities for the development of novel treatments and understanding of their natural history. Although the underlying genetic architecture of ASDs is not yet known, the literature demonstrates that it is not a monogenic disorder with mendelian inheritance, rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. This article reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of common and rare variant discoveries.
3. Giannandrea M, Bianchi V, Mignogna ML, Sirri A, Carrabino S, D’Elia E, Vecellio M, Russo S, Cogliati F, Larizza L, Ropers HH, Tzschach A, Kalscheuer V, Oehl-Jaschkowitz B, Skinner C, Schwartz CE, Gecz J, Van Esch H, Raynaud M, Chelly J, de Brouwer AP, Toniolo D, D’Adamo P. {{Mutations in the Small GTPase Gene RAB39B Are Responsible for X-linked Mental Retardation Associated with Autism, Epilepsy, and Macrocephaly}}. {Am J Hum Genet} (Feb 12);86(2):185-195.
Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities.
4. Goines P, Van de Water J. {{The immune system’s role in the biology of autism}}. {Curr Opin Neurol} (Feb 12)
PURPOSE OF REVIEW: The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. RECENT FINDINGS: The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed toward fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. Although studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. SUMMARY: In summary, the exciting research regarding the role of the immune system in autism spectrum disorders may have profound implications for diagnosis and treatment of this devastating disease.
5. Hoekstra RA, Happe F, Baron-Cohen S, Ronald A. {{Limited genetic covariance between autistic traits and intelligence: Findings from a longitudinal twin study}}. {Am J Med Genet B Neuropsychiatr Genet} (Feb 16)
Intellectual disability is common in individuals with autism spectrum conditions. However, the strength of the association between both conditions and its relevance to finding the underlying (genetic) causes of autism is unclear. This study aimed to investigate the longitudinal association between autistic traits and intelligence in a general population twin sample and to examine the etiology of this association. Parental ratings of autistic traits and performance on intelligence tests were collected in a sample of 8,848 twin pairs when the children were 7/8, 9, and 12 years old. Phenotypic and longitudinal correlations in the sample as a whole were compared to the associations in the most extreme scoring 5% of the population. The genetic and environmental influences on the overlap between autistic traits and IQ and on the stability of this relationship over time were estimated using structural equation modeling. Autistic traits were modestly negatively correlated to intellectual ability, both in the extreme scoring groups and among the full-range scores. The correlation was stable over time and was mainly explained by autistic trait items assessing communication difficulties. Genetic model fitting showed that autistic traits and IQ were influenced by a common set of genes and a common set of environmental influences that continuously affect these traits throughout childhood. The genetic correlation between autistic traits and IQ was only modest. These findings suggest that individual differences in autistic traits are substantially genetically independent of intellectual functioning. The relevance of these findings to future studies is discussed. (c) 2010 Wiley-Liss, Inc.
6. Kasari C, Lawton K. {{New directions in behavioral treatment of autism spectrum disorders}}. {Curr Opin Neurol} (Feb 12)
PURPOSE OF REVIEW: The review explores current trends in the behavioral intervention literature for children with an autism spectrum disorder (ASD) during 2008 and 2009. Noteworthy findings and intervention strategies are highlighted. Additionally, the quality of all reviewed studies is systematically evaluated. RECENT FINDINGS: During 2008 and 2009, there was nearly a quarter increase in the number of behavioral intervention studies, as well as more randomized controlled trials and approaches other than applied behavior analysis. Many of the studies investigated commonly used ASD intervention practices or novel treatments. A few were conducted with underserved populations, such as toddlers and adults with ASD. Social impairment was the focus of the largest number of intervention studies. A small percentage of studies were rated as high-quality. SUMMARY: Overall, the reviewed studies suggest that ASD-specific deficits can be improved through behavioral intervention. However, whereas progress continues to be made in our understanding of effective treatments for children with ASD, confidence in these findings would be improved with higher-quality studies.
7. Knaus TA, Silver AM, Dominick KC, Schuring MD, Shaffer N, Lindgren KA, Joseph RM, Tager-Flusberg H. {{Age-Related Changes in the Anatomy of Language Regions in Autism Spectrum Disorder}}. {Brain Imaging Behav};2009 (Mar 1);3(1):51-63.
Impairments in language and communication are core features of autism spectrum disorder (ASD). The anatomy of critical language areas has been studied in ASD with inconsistent findings. We used MRI to measure gray matter volume and asymmetry of Heschl’s gyrus, planum temporale, pars triangularis, and pars opercularis in 40 children and adolescents with ASD and 40 typically developing individuals, each divided into younger (7-11 years) and older (12-19 years) cohorts. The older group had larger left planum temporale volume and stronger leftward asymmetry than the younger group, regardless of diagnosis. The pars triangularis and opercularis together were larger in ASD than controls. Correlations between frontal language areas with language and symptom severity scores were significant in younger ASD children. Results suggest similar developmental changes in planum temporale anatomy in both groups, but group differences in pars triangularis and opercularis that may be related to language abilities and autism symptom severity.
8. McDonald ME, Paul JF. {{Timing of Increased Autistic Disorder Cumulative Incidence}}. {Environ Sci Technol} (Feb 16)
Autistic disorder (AD) is a severe neurodevelopmental disorder typically identified in early childhood. Both genetic and environmental factors are implicated in its etiology. The number of individuals identified as having autism has increased dramatically in recent years, but whether some proportion of this increase is real is unknown. If real, susceptible populations may have exposure to controllable exogenous stressors. Using literature AD data from long-term ( approximately 10-year) studies, we determined cumulative incidence of AD for each cohort within each study. These data for each study were examined for a changepoint year in which the AD cumulative incidence first increased. We used data sets from Denmark, California, Japan, and a worldwide composite of studies. In the Danish, California, and worldwide data sets, we found that an increase in AD cumulative incidence began about 1988-1989. The Japanese study (1988-1996) had AD cumulative incidence increasing continuously, and no changepoint year could be calculated. Although the debate about the nature of increasing autism continues, the potential for this increase to be real and involve exogenous environmental stressors exists. The timing of an increase in autism incidence may help in screening for potential candidate environmental stressors.
9. Mitka M. {{Rising autism rates still pose a mystery}}. {Jama} (Feb 17);303(7):602.
10. Stichter JP, Herzog MJ, Visovsky K, Schmidt C, Randolph J, Schultz T, Gage N. {{Social Competence Intervention for Youth with Asperger Syndrome and High-functioning Autism: An Initial Investigation}}. {J Autism Dev Disord} (Feb 17)
Individuals with high functioning autism (HFA) or Asperger Syndrome (AS) exhibit difficulties in the knowledge or correct performance of social skills. This subgroup’s social difficulties appear to be associated with deficits in three social cognition processes: theory of mind, emotion recognition and executive functioning. The current study outlines the development and initial administration of the group-based Social Competence Intervention (SCI), which targeted these deficits using cognitive behavioral principles. Across 27 students age 11-14 with a HFA/AS diagnosis, results indicated significant improvement on parent reports of social skills and executive functioning. Participants evidenced significant growth on direct assessments measuring facial expression recognition, theory of mind and problem solving. SCI appears promising, however, larger samples and application in naturalistic settings are warranted.
11. Whalon KJ, Otaiba SA, Delano ME. {{Evidence-Based Reading Instruction for Individuals with Autism Spectrum Disorders}}. {Focus Autism Other Dev Disabl};2009 (Mar 1);24(1):3-16.
Legislation mandates that all children, including children with autism spectrum disorders (ASD) be taught to read in ways that are consistent with reading research, and target the five components of evidence-based reading instruction: phonemic awareness, phonics, reading fluency, vocabulary and comprehension strategies. The purpose of this review is to synthesize the literature on reading instruction for children with ASD that encompasses one or more of the five components of reading. The review yielded 11 studies with 61 participants ages 4 to 17. Results indicate that children with ASD can benefit from reading instruction consistent with reading research. Research in this area is still preliminary, and more research is needed to guide practice. Possible directions for future research are provided.
12. Wisniowiecka-Kowalnik B, Nesteruk M, Peters SU, Xia Z, Cooper ML, Savage S, Amato RS, Bader P, Browning MF, Haun CL, Duda AW, 3rd, Cheung SW, Stankiewicz P. {{Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay}}. {Am J Med Genet B Neuropsychiatr Genet} (Feb 16)
NRXN1 is highly expressed in brain and has been shown recently to be associated with ASD, schizophrenia, cognitive and behavioral abnormalities, and alcohol and nicotine dependence. We present three families, in whom we identified intragenic rearrangements within NRXN1 using a clinical targeted oligonucleotide array CGH. An approximately 380 kb deletion was identified in a woman with Asperger syndrome, anxiety, and depression and in all four of her children affected with autism, anxiety, developmental delay, and speech delay but not in an unaffected child. An approximately 180 kb tandem duplication was found in a patient with autistic disorder and cognitive delays, and in his mother and younger brother who have speech delay. An approximately 330 kb tandem duplication was identified in a patient with autistic features. As predicted by conceptual translation, all three genomic rearrangements led to the premature truncation of NRXN1. Our data support previous observations that NRXN1 may be pathogenic in a wide variety of psychiatric diseases, including autism spectrum disorder, global developmental delay, anxiety, and depression. (c) 2010 Wiley-Liss, Inc.
