1. Balemans MC, Huibers MM, Eikelenboom NW, Kuipers AJ, Summeren RC, Pijpers MM, Tachibana M, Shinkai Y, van Bokhoven H, Zee CE. {{Reduced exploration, increased anxiety, and altered social behavior: autistic-like features of Euchromatin histone methyltransferase 1 heterozygous knockout mice}}. {Behav Brain Res};2009 (Nov 4)
The 9q34.3 subtelomeric deletion syndrome is a newly defined mental retardation syndrome, caused by haplo-insufficiency of the Euchromatin Histone Methyltransferase 1 (EHMT1) gene. Patients also have childhood hypotonia, facial dysmorphisms, delay in reaching developmental milestones, and behavioral problems like aggressive outbursts, hypoactivity, or autistic-like features. Male and female heterozygous Ehmt1 knockout mice (Ehmt1(+/-), aged 1-20 months, kept on a C57BL/6J background), were used to investigate whether they mimic the patients behavioral characteristics by comparing their behavior to wildtype littermates. The Ehmt1(+/-) mice revealed reduced activity and exploration, with increased anxiety compared to wildtype mice when exposed to novel environments in the open field, object exploration, marble burying, light-dark box, mirrored chamber and t-maze tests. They also demonstrated diminished social play when encountering a mouse from a different litter, and a delayed or absent response to social novelty when exposed to a stranger mouse. However, no differences in phenotyper home cage locomotor activity or rotarod motor function were observed between Ehmt1(+/-) and wildtype mice. Together, these results indicate that the hypoactivity and the autistic-like features of 9q34.3 subtelomeric deletion syndrome patients are recapitulated in this Ehmt1(+/-) mouse model, and that the hypoactivity is apparently not caused by any motor dysfunction. Together, these observations make it plausible that the Ehmt1(+/-) mouse is a faithful mammalian model for the autistic-like behavioral features of patients with the 9q34.3 subtelomeric deletion syndrome.
2. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB. {{Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism Spectrum Disorders}}. {Biol Psychiatry};2009 (Nov 6)
BACKGROUND: A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. METHODS: In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger’s Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. RESULTS: In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. CONCLUSIONS: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders.
3. Hughes JR. {{Update on autism: A review of 1300 reports published in 2008}}. Epilepsy Behav;2009 (Nov 5)
This publication, by reviewing 1300 studies published on autism in 2008, represents an update on this topic. Results include possible parental influences, maternal conditions, and studies on genes and chromosomes. Possible etiological factors involve the « extreme male brain, » defects in the mirror neuron system, vaccines, underconnectivity, disorders of central coherence, and many other more specific etiologies. Assessments or tests for autism are also reviewed. Characteristics of autistic individuals include repetitive behavior, language disorders, sleep disturbances, social problems, joint attention disorders, seizures, allergic reactions, and various behavioral changes. Cognitive changes involve IQ, reasoning, and verbal and language disorders. The savant syndrome is a fascinating phenomenon, at times seen in autistic individuals. Neurophysiological and neuroanatomical changes are also reviewed, as are comorbid conditions. Finally, treatment involves various medications including risperidone, ziprasidone, and antipsychotic drugs, as well as different procedures such as magnetic stimulation, acupuncture, and hyperbaric oxygen therapy. As mentioned in the 2007 survey, nearly every conceivable problem that a child can have may be found in these unfortunate children and nearly every conceivable etiology has been mentioned to account for this serious disorder.
4. Hutsler JJ, Zhang H. {{Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders}}. {Brain Res};2009 (Nov 5)
Multiple types of indirect evidence have been used to support theories of altered cortical connectivity in autism spectrum disorders (ASD). In other developmental disorders reduced spine expression is commonly found, while conditions such as fragile X syndrome show increased spine densities. Despite its relevance to theories of altered cortical connectivity, synaptic spine expression has not been systematically explored in ASD. Here we examine dendritic spines on Golgi-impregnated cortical pyramidal cells in the cortex of ASD subjects and age-matched control cases. Pyramidal cells were studied within both the superficial and deep cortical layers of frontal, temporal, and parietal lobe regions. Relative to controls, spine densities were greater in ASD subjects. In analyses restricted to the apical dendrites of pyramidal cells, greater spine densities were found predominantly within layer II of each cortical location and within layer V of the temporal lobe. High spine densities were associated with decreased brain weights and were most commonly found in ASD subjects with lower levels of cognitive functioning. Greater spine densities in ASD subjects provides structural support for recent suggestions of connectional changes within the cerebral cortex that may result in altered cortical computations.
5. Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N. {{Association between autism and variants in the wingless-type MMTV integration site family member 2 ( WNT2) gene}}. {Int J Neuropsychopharmacol};2009 (Nov 9):1-7.
Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time. We conducted a case-control study of nine single nucleotide polymorphisms (SNPs) within the WNT2 gene in 170 patients with autism and 214 normal controls in a Japanese population. We then conducted a TDT analysis in 98 autistic families (trios) to replicate the results of the case-control study. In the case-control study, three SNPs (rs3779547, rs4727847 and rs3729629), two major individual haplotypes (A-T-C and G-G-G, consisting of rs3779547, rs4727847, and rs3729629), and global probability values of the haplotype distributions in the same region (global p=0.0091) showed significant associations with autism. Furthermore, all of these significant associations were also observed in the TDT analysis. Our findings provide evidence for a significant association between WNT2 and autism. Considering the important role of the WNT2 gene in brain development, our results therefore indicate that the WNT2 gene is one of the strong candidate genes for autism.
6. Suzuki K, Nishimura K, Sugihara G, Nakamura K, Tsuchiya KJ, Matsumoto K, Takebayashi K, Isoda H, Sakahara H, Sugiyama T, Tsujii M, Takei N, Mori N. {{Metabolite alterations in the hippocampus of high-functioning adult subjects with autism}}. {Int J Neuropsychopharmacol};2009 (Nov 9):1-6.
The aim of the present study was to investigate metabolite alterations in the hippocampal formation as they relate to aggression in high-functioning adults with autism. We measured concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr+PCr) in the hippocampal formation by proton magnetic resonance spectroscopy in 12 non-medicated male subjects with autism and 12 age- and sex-matched controls. Aggression was scored in the autistic subjects using the Buss-Perry Aggression Questionnaire. The concentrations of Cho and Cr+PCr in the hippocampal formation in autistic subjects were significantly higher than the corresponding values in control subjects, and a significant positive correlation was observed between the concentrations of these metabolites in the hippocampal formation and scores on the Buss-Perry Aggression Questionnaire in autistic subjects. Results suggest that high-functioning adult subjects with autism have abnormal metabolite concentrations in the hippocampal formation, which may in part account for their aggression.
7. Weiss LA. {{Autism genetics: emerging data from genome-wide copy-number and single nucleotide polymorphism scans}}. {Expert Rev Mol Diagn};2009 (Nov);9(8):795-803.
Autism and related traits are highly heritable but cannot be explained by currently known genetic risk factors. Therefore, the advent of genome-wide single nucleotide polymorphism (SNP) and copy number variant (CNV) microarray technologies heralded identification of additional autism loci. CNVs associated with autism seem to show variable expressivity, also leading to other phenotypes, such as schizophrenia, mental retardation/developmental delay and epilepsy. Initial genome-wide SNP-association studies have each identified a single novel associated locus with modest effect. Based on the lessons from other complex common disease, larger sample sizes and meta-analyses are likely to identify additional SNP loci, and the genes implicated may act on multiple related disorders. Even if common alleles or rare variants hold little predictive value, neurodevelopmental pathways disrupted in autism may be identified. Future research might yet uncover common CNV risk loci and rare single nucleotide risk alleles, which are currently difficult to detect. The genetic architecture and phenotypic heterogeneity identified so far suggest additional approaches, such as population-based research and study of relevant neurobiological endophenotypes.
