1. Asahi Y, Kubota K, Omichi S. {{Dose requirements for propofol anaesthesia for dental treatment for autistic patients compared with intellectually impaired patients}}. {Anaesth Intensive Care};2009 (Jan);37(1):70-73.
We had clinical grounds to suspect that patients with autism had greater propofol requirements during dental procedures than patients with intellectual impairment without autism. This hypothesis was tested by an audit of a standard anaesthetic technique. The audit was approved by our Hospital Ethics Committee. We compared the propofol requirements and effect using a standardised protocol during dental treatment in 56 autistic patients (age range three to 35 years) and 56 intellectually impaired patients (age range four to 42 years). Patients in each disability group were divided into three subgroups by age: six years or younger, seven to 19 years and 20 years or older. Combative patients received oral midazolam premedication, other patients received a single intravenous bolus of midazolam at induction. Otherwise, standardised propofol boluses and infusion were the only anaesthetic agents used. The propofol infusion rates of the intellectually impaired group showed significant decline with age (propofol rate of requirement mg x kg(-1) x h(-1), mean [SD]): < six years 13.6 (3.6), seven to 19 years 9.5 (3.0) (P = 0.008 cf < six years group), > 19 years group 8.5 (2.4) (P = 0.001 cf < six years group). The propofol requirement was greater in the autism group than in the intellectual disability group, and the proportion of the cases where bolus propofol administration was needed after induction was significantly higher in the autistic patient group than in the intellectually impaired patients (P < 0.002). This suggests that autistic patients have greater propofol requirements for anaesthesia during ordinary dental treatment compared with intellectually impaired patients.
2. Gong X, Delorme R, Fauchereau F, Durand CM, Chaste P, Betancur C, Goubran-Botros H, Nygren G, Anckarsater H, Rastam M, Gillberg IC, Kopp S, Mouren-Simeoni MC, Gillberg C, Leboyer M, Bourgeron T. {{An investigation of ribosomal protein L10 gene in autism spectrum disorders}}. {BMC Med Genet};2009;10:7.
BACKGROUND: Autism spectrum disorders (ASD) are severe neurodevelopmental disorders with the male:female ratio of 4:1, implying the contribution of X chromosome genetic factors to the susceptibility of ASD. The ribosomal protein L10 (RPL10) gene, located on chromosome Xq28, codes for a key protein in assembling large ribosomal subunit and protein synthesis. Two non-synonymous mutations of RPL10, L206M and H213Q, were identified in four boys with ASD. Moreover, functional studies of mutant RPL10 in yeast exhibited aberrant ribosomal profiles. These results provided a novel aspect of disease mechanisms for autism–aberrant processes of ribosome biosynthesis and translation. To confirm these initial findings, we re-sequenced RPL10 exons and quantified mRNA transcript level of RPL10 in our samples. METHODS: 141 individuals with ASD were recruited in this study. All RPL10 exons and flanking junctions were sequenced. Furthermore, mRNA transcript level of RPL10 was quantified in B lymphoblastoid cell lines (BLCL) of 48 patients and 27 controls using the method of SYBR Green quantitative PCR. Two sets of primer pairs were used to quantify the mRNA expression level of RPL10: RPL10-A and RPL10-B. RESULTS: No non-synonymous mutations were detected in our cohort. Male controls showed similar transcript level of RPL10 compared with female controls (RPL10-A, U = 81, P = 0.7; RPL10-B, U = 61.5, P = 0.2). We did not observe any significant difference in RPL10 transcript levels between cases and controls (RPL10-A, U = 531, P = 0.2; RPL10-B, U = 607.5, P = 0.7). CONCLUSION: Our results suggest that RPL10 has no major effect on the susceptibility to ASD.
3. Henningsson S, Jonsson L, Ljunggren E, Westberg L, Gillberg C, Rastam M, Anckarsater H, Nygren G, Landen M, Thuresson K, Betancur C, Leboyer M, Gillberg C, Eriksson E, Melke J. {{Possible association between the androgen receptor gene and autism spectrum disorder}}. {Psychoneuroendocrinology};2009 (Jun);34(5):752-761.
Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
4. Inglese MD. {{Caring for children with autism spectrum disorder. Part II: screening, diagnosis, and management}}. {J Pediatr Nurs};2009 (Feb);24(1):49-59.
Recent emphasis on the importance of early identification and intervention for children with autism spectrum disorder (ASD) highlights the need for nurses in the community and primary care settings to learn to screen for ASD in children. In addition, given that ASD now affects 1 in 150 children, it is probable that nurses in a variety of settings, at all practice levels, will encounter children with ASD. Nurses need to be able to support families, educate parents, manage basic issues relevant to ASD, and advocate for these children and their families.
5. Inglese MD, Elder JH. {{Caring for children with autism spectrum disorder. Part I: prevalence, etiology, and core features}}. {J Pediatr Nurs};2009 (Feb);24(1):41-48.
Autism spectrum disorder (ASD) affects 1 in 150 children and has been gaining national attention over the past decade. Given the prevalence of this disorder, there is a high probability that pediatric nurses will care for a child with ASD, regardless of the setting in which they work. Children with ASD traverse the primary care outpatient setting, schools, subspecialty clinics, and inpatient units. A basic understanding of the current issues regarding prevalence and etiology, coupled with knowledge of the core features of ASD, will help pediatric nurses in all settings and at various practice levels better care for these children.
6. Keary CJ, Minshew NJ, Bansal R, Goradia D, Fedorov S, Keshavan MS, Hardan AY. {{Corpus callosum volume and neurocognition in autism}}. {J Autism Dev Disord};2009 (Jun);39(6):834-841.
The corpus callosum has recently been considered as an index of interhemispheric connectivity. This study applied a novel volumetric method to examine the size of the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ-matched controls and to investigate the relationship between this structure and cognitive measures linked to interhemispheric functioning. Participants with autism displayed reductions in total corpus callosum volume and in several of its subdivisions. Relationships were also observed between volumetric alterations and performance on several cognitive tests including the Tower of Hanoi test. These findings provide further evidence for anatomical alterations in the corpus callosum in autism, but warrant additional studies examining the relationship of this structure and specific measures of interhemispheric connectivity.
7. Larsson EL, Aaro S, Ahlinder P, Normelli H, Tropp H, Oberg B. {{Long-term follow-up of functioning after spinal surgery in patients with Rett syndrome}}. {Eur Spine J};2009 (Apr);18(4):506-511.
In a prospective study, 23 consecutive girls with Rett syndrome and neuromuscular scoliosis were evaluated for functioning at a long-term follow-up. The patients had mostly improved, which was confirmed by their parents. Rett syndrome is associated with neuromuscular scoliosis and has a typically long C-shaped thoracolumbar kyphoscoliosis. Prospective long-term follow-up studies related to these patients’ total situation are sparse. Most studies focus on the Cobb angle of the scoliosis, whereas parents are mainly concerned about the girls’ continued functioning. Twenty-three patients with Rett syndrome and neuromuscular scoliosis were evaluated preoperatively from 1993 to 2002. At follow-up, 19 patients remained in the study. Three patients died (not due to surgery), and one patient could not participate because it was too far to travel. Mean follow-up time was 74 months (range 49-99 months). The assessments comprised the sitting balance, seating supports in wheelchair, weight distribution, time used for rest, care given, and angle of scoliosis. Follow-up questionnaires and two-open-ended questions about the positive and negative effects of surgery were sent to parents. Sitting balance, number of seating supports in wheelchair, weight distribution, time used for rest, and the Cobb angle had all improved after surgery. The parents assessed improvement in seating position, daily activities, time used for rest, and cosmetic appearance. We can conclude that the stabilized spine resulted in sufficient strength to keep the body upright with the possibility of looking around at the surroundings more easily. The girls got better seating position with less need for seating adaptations in the wheelchair and with reduced time needed for resting during the day. Finally we can conclude that the indication for surgery is to get a better posture which lead to less risk of pressure sores, and that un upright position lead to better possibility to easily breath with fewer episodes of pneumonia and a better general health as result. The evidence of positive surgical effects for girls with Rett syndrome is of great importance in indication for surgery in the decision-making process.
8. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M. {{Elevated immune response in the brain of autistic patients}}. {J Neuroimmunol};2009 (Feb 15);207(1-2):111-116.
This study determined immune activities in the brain of ASD patients and matched normal subjects by examining cytokines in the brain tissue. Our results showed that proinflammatory cytokines (TNF-alpha, IL-6 and GM-CSF), Th1 cytokine (IFN-gamma) and chemokine (IL-8) were significantly increased in the brains of ASD patients compared with the controls. However the Th2 cytokines (IL-4, IL-5 and IL-10) showed no significant difference. The Th1/Th2 ratio was also significantly increased in ASD patients. Conclusion: ASD patients displayed an increased innate and adaptive immune response through the Th1 pathway, suggesting that localized brain inflammation and autoimmune disorder may be involved in the pathogenesis of ASD.
9. Moraine C, Bonnet-Brilhault F, Laumonnier F, Gomot M. {{Could autism with mental retardation result from digenism and frequent de novo mutations?}}. {World J Biol Psychiatry};2009;10(4 Pt 3):1030-1036.
The high concordance for autism symptoms in monozygotic twin-pairs compared to di-zygotic twins and/or non-twin sib-ships suggests a high genetic determinism in autism. Those results have hypothesized multi-factorial determinism in accordance with family studies and mathematical models. However, linkage and association or candidate gene strategies have failed to-date to identify clearly involved mechanisms. Mental retardation (MR) is known as frequently associated to autism. Multiplex XLMR pedigrees have been reported with only one mutated patient having autism and MR: different X-located MR genes have been shown to be involved (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be « autism genes ». Tuberous sclerosis studies and report of numerous autosomal domains shown deleted in MR-autistic subjects suggest that several autosomal dominant (AD) genes could be also involved in MR with autism. Whereas multiplex AD-MR families are rare, AD de novo mutations could explain numerous sporadic situations of non-specific MR and of autism with MR, in accordance with twin studies. Finally, we hypothesize that in those autistic subjects with mendelian MR, the XL-MR or AD-MR gene (G1) would pave the way for a second Mendelian factor (G2) responsible for autism symptoms.
10. Murawski NJ, Brown KL, Stanton ME. {{Interstimulus interval (ISI) discrimination of the conditioned eyeblink response in a rodent model of autism}}. {Behav Brain Res};2009 (Jan 23);196(2):297-303.
Rats exposed to valproic acid (VPA) on gestational day 12 (GD12) have been advanced as a rodent model of autism [Arndt TL, Stodgell, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23: 189-99.]. These rats show cerebellar anomalies and alterations in eyeblink conditioning that are associated with autism. Autistic humans and VPA-exposed rats show normal responses to conditioned and unconditioned stimuli, but they show marked differences from comparison groups in acquisition, magnitude, and timing of the conditioned response (CR). This study examined VPA-induced eyeblink CR timing differences by training rats on an interstimulus interval (ISI) discrimination task, in which two distinct conditioned stimuli (CS; tone and light) are paired with the same unconditioned stimulus (US; periocular shock) at two distinct CS-US intervals. Previous findings suggest that this task would produce abnormally large and prematurely timed CRs for VPA-exposed rats relative to controls. Adult male Long-Evans rats that were exposed to either VPA or saline on GD 12.5 were trained on an ISI discrimination task [Brown KL, Pagani JH, Stanton ME. The ontogeny of interstimulus interval (ISI) discrimination of the conditioned eyeblink response in rats. Behav Neurosci 2006;120: 1057-70.]. In support of earlier findings, we observed early acquisition and enhanced magnitude of the CR in VPA rats compared with controls on long CS trials. VPA rats also showed prematurely timed CRs to long- CS trials, but not to short- CS trials. The ISI discrimination procedure used in the current study reveals differential timed responses in this animal model of autism not previously seen.
11. Nishiyama T, Taniai H, Miyachi T, Ozaki K, Tomita M, Sumi S. {{Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs)}}. {J Hum Genet};2009 (Jan);54(1):56-61.
Although there is accumulating evidence that intelligence quotient (IQ) indexes some aspects of the autistic spectrum disorders (ASDs), the causal relationship between autistic traits and IQ remains controversial. We examined the sources of covariation between autistic traits and IQ. As males have a four times greater risk of ASDs than females, gender-specific effects were also explored. Autistic traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited Cholesky structural equation models were used to decompose the correlations between autistic traits and IQ into genetic and environmental components, including sex-specific factors. Genetic correlations between autistic traits and IQ were high and not significantly different between boys and girls (-0.94 and -0.95, respectively), but genetic factors underlying the autistic traits were not entirely shared with the IQ. The individual-specific environmental correlation between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for girls. There is a substantial overlap between the genetic factors that influence individual variation in autistic traits and IQ, irrespective of gender. The individual life experiences that increase autistic traits, however, have a moderate overlap with those that contribute to individual IQs.
12. Orabona GM, Griesi-Oliveira K, Vadasz E, Bulcao VL, Takahashi VN, Moreira ES, Furia-Silva M, Ros-Melo AM, Dourado F, Matioli SR, Otto P, Passos-Bueno MR. {{HTR1B and HTR2C in autism spectrum disorders in Brazilian families}}. {Brain Res};2009 (Jan 23);1250:14-19.
Autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD.
13. Schwartz CB, Henderson HA, Inge AP, Zahka NE, Coman DC, Kojkowski NM, Hileman CM, Mundy PC. {{Temperament as a predictor of symptomotology and adaptive functioning in adolescents with high-functioning autism}}. {J Autism Dev Disord};2009 (Jun);39(6):842-855.
Variation in temperament is characteristic of all people but is rarely studied as a predictor of individual differences among individuals with autism. Relative to a matched comparison sample, adolescents with High-Functioning Autism (HFA) reported lower levels of Surgency and higher levels of Negative Affectivity. Variability in temperament predicted symptomotology, social skills, and social-emotional outcomes differently for individuals with HFA than for the comparison sample. This study is unique in that temperament was measured by self-report, while all outcome measures were reported by parents. The broader implications of this study suggest that by identifying individual variability in constructs, such as temperament, that may influence adaptive functioning, interventions may be developed to target these constructs and increase the likelihood that individuals with HFA will achieve more adaptive life outcomes.
14. Tsuji H, Miyawaki D, Kawaguchi T, Matsushima N, Horino A, Takahashi K, Suzuki F, Kiriike N. {{Relationship of hypersensitivity to anxiety and depression in children with high-functioning pervasive developmental disorders}}. {Psychiatry Clin Neurosci};2009 (Apr);63(2):195-201.
AIMS: Sensory-perceptual abnormalities, which include hyper- and hyposensitivity, have been identified by numerous researchers as prevalent in individuals with pervasive developmental disorders (PDD). Hypersensitivity has a greater impact on PDD patients’ daily lives than hyposensitivity. The purpose of the present study was to clarify the relationship of hypersensitivity to anxiety, depression and other psychopathology in children with PDD. METHODS: Sixty-four children were divided into a hypersensitivity group (HG; n = 43) and a non-hypersensitivity group (non-HG; n = 21), and compared for anxiety, depression and other psychopathology on the Child Behavior Checklist (CBCL), State-Trait Anxiety Inventory for Children (STAIC) and Children’s Depression Inventory (CDI). RESULTS: The HG group had significantly higher scores than the non-HG group in Total, Internalizing, and Somatic complaints on the CBCL. On STAIC, the mean sore of Total Score, State Score and Trait Score in the HG group tended to be higher than in the non-HG group, but the difference was not significant. The score on the CDI in the HG group was significantly higher than that in the non-HG group. CONCLUSION: PDD children with hypersensitivity have more serious psychopathologies, especially internalizing symptoms including depression.
