1. {{Abstracts of the European Academy of Childhood Disability 23rd Annual Meeting. June 8-11, 2011. Rome, Italy}}. {Dev Med Child Neurol};2011 (Jun);53 Suppl 3:1-69.

2. Al-Farsi YM, Al-Sharbati MM, Al-Farsi OA, Al-Shafaee MS, Brooks DR, Waly MI. {{Brief report: prevalence of autistic spectrum disorders in the sultanate of oman}}. {J Autism Dev Disord};2011 (Jun);41(6):821-825.

Prevalence of autistic spectrum disorders (ASD) in Oman is unknown. We conducted a cross-sectional study to estimate the prevalence of ASD among 0-14 year old children. Diagnoses were made as per DSM-IV-TR criteria and supplemented with information collected with the standard Childhood Autism Rating Scale (CARS) questionnaire. A total 113 cases of ASD were enumerated nationwide, indicating an overall prevalence of 1.4 (95% CI 1.2, 1.7) cases per 10,000 children aged 0-14 years. More prevalent cases were among boys (75%) and among low-income families. Ritualistic interests were more common among girls as an onset-symptom compared to boys (p = 0.03). The reported low prevalence of ASD in Oman is likely due to under-diagnosis and under-reporting.

3. Allanson JE, Hennekam RC, Moog U, Smeets EE. {{Rett syndrome: A study of the face}}. {Am J Med Genet A};2011 (May 27)

Rett syndrome is a unique disorder of neurodevelopment that is characterized by an evolving behavioral and developmental phenotype, which emerges after an apparently normal early infantile period. It almost exclusively affects females. The face of Rett syndrome is said to resemble that of Angelman syndrome, although there seems little objective support for this impression and it is not a concept with universal support. This observational and anthropometric study was carried out to define the key facial characteristics of females with Rett syndrome and to evaluate whether any changes of significance occur with age. Thirty-seven affected Caucasian females, from 2 to 20 years of age, were evaluated. Thirty-five of them had a documented mutation in MECP2 while the remaining two fulfilled the clinical criteria for Rett syndrome and had been diagnosed by an experienced clinician. Few unusual facial features were noted. Almost all facial measurements were within the normal range although head circumference tended to fall below the normal range with increasing age. The pattern of measurements was constant over time, with the exception of increased facial width in the under 3-year-old girls. The face of Rett syndrome does not demonstrate marked prognathism, wide mouth, spaced teeth or striking microcephaly, all features of Angelman syndrome. Thus, while Rett and Angelman syndromes have similar clinical, neurological, and behavioral phenotypes, they do not appear to share similar facial features. (c) 2011 Wiley-Liss, Inc.

4. Azmitia EC, Singh JS, Whitaker-Azmitia PM. {{Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors}}. {Neuropharmacology};2011 (Jun);60(7-8):1347-1354.

Imaging studies of serotonin transporter binding or tryptophan retention in autistic patients suggest that the brain serotonin system is decreased. However, treatment with drugs which increase serotonin (5-HT) levels, specific serotonin reuptake inhibitors (SSRIs), commonly produce a worsening of the symptoms. In this study we examined 5-HT axons that were immunoreactive to a serotonin transporter (5-HTT) antibody in a number of postmortem brains from autistic patients and controls with no known diagnosis who ranged in age from 2 to 29 years. Fine, highly branched, and thick straight fibers were found in forebrain pathways (e.g. medial forebrain bundle, stria terminalis and ansa lenticularis). Many immunoreactive varicose fine fibers were seen in target areas (e.g. globus pallidus, amygdala and temporal cortex). Morphometric analysis of the stained axons at all ages studied indicated that the number of serotonin axons was increased in both pathways and terminal regions in cortex from autism donors. Our findings provide morphological evidence to warrant caution when using serotonin enhancing drugs (e.g. SSRIs and receptor agonist) to treat autistic children. This article is part of a Special Issue entitled ‘Trends in neuropharmacology: in memory of Erminio Costa’.

5. Beherec L, Lambrey S, Quilici G, Rosier A, Falissard B, Guillin O. {{Retrospective review of clozapine in the treatment of patients with autism spectrum disorder and severe disruptive behaviors}}. {J Clin Psychopharmacol};2011 (Jun);31(3):341-344.

Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 +/- 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs.

6. Ben-Yizhak N, Yirmiya N, Seidman I, Alon R, Lord C, Sigman M. {{Pragmatic language and school related linguistic abilities in siblings of children with autism}}. {J Autism Dev Disord};2011 (Jun);41(6):750-760.

Siblings of probands with autism spectrum disorders are at higher risk for developing the broad autism phenotype (BAP). We compared the linguistic abilities (i.e., pragmatic language, school achievements, and underling reading processes) of 35 school-age siblings of children with autism (SIBS-A) to those of 42 siblings of children with typical development. Results indicated lower pragmatic abilities in a subgroup of SIBS-A identified with BAP related difficulties (SIBS-A-BAP) whereas school achievements and reading processes were intact. Furthermore, among SIBS-A-BAP, significant negative correlations emerged between the severity scores on the Autism Diagnostic Observation Schedule and full and verbal IQ scores. These results are discussed in the context of the developmental trajectories of SIBS-A and in relation to the BAP.

7. Bergersen LH, Sander M, Storm-Mathisen J. {{What the nose knows, what the eyes see, how we feel, how we learn, how we understand motor acts, why « YY » is essential for ion transport, how epigenetics meet neurobiology in Rett syndrome: Seven topics at the 2010 Kavli Prize Symposium on Neuroscience}}. {Neuroscience};2011 (May 27)

8. Berger-Sweeney J. {{Cognitive deficits in Rett syndrome: What we know and what we need to know to treat them}}. {Neurobiol Learn Mem};2011 (May 23)

Rett syndrome is an autism spectrum disorder and a leading cause of severe mental retardation in girls. The nature of the cognitive abnormalities in Rett, as described in humans and other animal models, and its potential reversibility and treatment are the subject of this review. Rett syndrome is associated with severe mental retardation and a host of impairments that include social and motor deficits, and respiratory and bone abnormalities. More than 80% of Rett girls have mutations in the gene that encodes MeCP2, which is a protein with a complex set of functions that include transcriptional repression and activation. The complex phenotype associated with Rett and the knowledge of the causal genetic mutation provide a unique opportunity within the autism spectrum to explore the relationship between transcriptional control, brain abnormalities and specific behavioral functions, importantly the elusive cognitive dysfunctions associated with mental retardation. The nature of the cognitive abnormalities related to Rett and the potential reversibility and treatment of these abnormalities has not been studied as extensively as some of the other aspects of the Rett phenotype. The cognitive phenotype associated with Rett is also less well studied relative to that in other well known developmental disorders, such as Down syndrome and Fragile X. Nevertheless, some recent studies provide hope that the cognitive impairments, as well as other symptoms of Rett, can be rescued.

9. Botkin JR. {{Newborn screening for fragile x syndrome: do we care what parents think?}}. {Pediatrics};2011 (Jun);127(6):e1593-1594.

10. Bowers K, Li Q, Bressler J, Avramopoulos D, Newschaffer C, Fallin MD. {{Glutathione pathway gene variation and risk of autism spectrum disorders}}. {J Neurodev Disord};2011 (Jun);3(2):132-143.

Despite evidence that autism is highly heritable with estimates of 15 or more genes involved, few studies have directly examined associations of multiple gene interactions. Since inability to effectively combat oxidative stress has been suggested as a mechanism of autism, we examined genetic variation 42 genes (308 single-nucleotide polymorphisms (SNPs)) related to glutathione, the most important antioxidant in the brain, for both marginal association and multi-gene interaction among 318 case-parent trios from The Autism Genetic Resource Exchange. Models of multi-SNP interactions were estimated using the trio Logic Regression method. A three-SNP joint effect was observed for genotype combinations of SNPs in glutaredoxin, glutaredoxin 3 (GLRX3), and cystathione gamma lyase (CTH); OR = 3.78, 95% CI: 2.36, 6.04. Marginal associations were observed for four genes including two involved in the three-way interaction: CTH, alcohol dehydrogenase 5, gamma-glutamylcysteine synthetase, catalytic subunit and GLRX3. These results suggest that variation in genes involved in counterbalancing oxidative stress may contribute to autism, though replication is necessary.

11. Boyle CA, Boulet S, Schieve LA, Cohen RA, Blumberg SJ, Yeargin-Allsopp M, Visser S, Kogan MD. {{Trends in the Prevalence of Developmental Disabilities in US Children, 1997-2008}}. {Pediatrics};2011 (Jun);127(6):1034-1042.

OBJECTIVE: To fill gaps in crucial data needed for health and educational planning, we determined the prevalence of developmental disabilities in US children and in selected populations for a recent 12-year period. PARTICIPANTS AND METHODS: We used data on children aged 3 to 17 years from the 1997-2008 National Health Interview Surveys, which are ongoing nationally representative samples of US households. Parent-reported diagnoses of the following were included: attention deficit hyperactivity disorder; intellectual disability; cerebral palsy; autism; seizures; stuttering or stammering; moderate to profound hearing loss; blindness; learning disorders; and/or other developmental delays. RESULTS: Boys had a higher prevalence overall and for a number of select disabilities compared with girls. Hispanic children had the lowest prevalence for a number of disabilities compared with non-Hispanic white and black children. Low income and public health insurance were associated with a higher prevalence of many disabilities. Prevalence of any developmental disability increased from 12.84% to 15.04% over 12 years. Autism, attention deficit hyperactivity disorder, and other developmental delays increased, whereas hearing loss showed a significant decline. These trends were found in all of the sociodemographic subgroups, except for autism in non-Hispanic black children. CONCLUSIONS: Developmental disabilities are common and were reported in approximately 1 in 6 children in the United States in 2006-2008. The number of children with select developmental disabilities (autism, attention deficit hyperactivity disorder, and other developmental delays) has increased, requiring more health and education services. Additional study of the influence of risk-factor shifts, changes in acceptance, and benefits of early services is needed.

12. Brambring M. {{Response to Hobson’s Letter: Congenital Blindness and Autism}}. {J Autism Dev Disord};2011 (May 28)

Contrary scientific positions between Hobson and Brambring regarding the connectedness of congenital blindness and autism.

13. Brock J. {{Commentary: Complementary approaches to the developmental cognitive neuroscience of autism – reflections on Pelphrey et al. (2011)}}. {J Child Psychol Psychiatry};2011 (Jun);52(6):645-646.

14. Buehler MR. {{A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder}}. {Med Hypotheses};2011 (Jun);76(6):863-870.

Autism, an incurable neurodevelopmental brain disorder, is a complex psychopathology in which the affected individual cannot effectively self-regulate their sensory inputs toward coherent and focused motor outputs. There have been many hypotheses as to the etiology of autism – genetics, neurotransmitter imbalances, early childhood immunizations, xenobiotic and teratogenic agents, and maternal infection; the disorder can perhaps be studied best under the field of « Psychoneuroimmunology », which analyzes systemic and psychopathologies from an integrated approach through the combined effects of the nervous, immune, and endocrine systems. Using principles of psychoneuroimmunology along with previously established but yet un-linked scientific principles and observations, this paper proposes a neuroimmune-based mechanistic hypothesis for the etiology of autism that connects elevated levels of maternal pro-inflammatory cytokines to autistic symptoms in her offspring through a logical sequence of events. While both researchers and clinicians often note correlations between pro-inflammatory cytokine levels and autistic symptoms in affected individuals, no specific mechanism has been documented that logically and directly connects the two. I propose that pro-inflammatory cytokines arising from maternal inflammation, infection, and, possibly, autoimmunity, pass through the placenta; enter the fetal circulation; cross the fetal blood-brain barrier (BBB); and cause aberrant neuronal growth and plasticity within the fetal brain via a « cytokine-storm ». Microglia and astrocyte stimulation lead to a positive-feedback loop that also facilitates the development of a chronic inflammatory environment within the fetus, pre-disposing it to lifelong comorbid psychiatric and systemic pathologies. Such a mechanism could account for many of the observed symptoms and behaviors of autistic individuals such as hyper-sensitivity to environmental stimuli, object fixation, echolalia, repetitive physical behaviors, chronic enterocolitis, autoimmune disease, and, at the extreme, savantism. The thiazolidinedione pioglitazone (and possibly rosiglitazone), a non-steroidal anti-inflammatory drug (NSAID), which is commonly used to lower blood glucose levels and associated inflammatory markers in patients with diabetes, and histamine receptor blockers, as well as monitoring and limiting sucrose-containing foods, might prove to be effective preventative therapies for the development of autism in the fetus for pregnant women displaying either a cytokine-induced depression or other elevated systemic inflammatory state conditions.

15. Campbell DB, Datta D, Jones ST, Batey Lee E, Sutcliffe JS, Hammock EA, Levitt P. {{Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder}}. {J Neurodev Disord};2011 (Jun);3(2):101-112.

Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, communication, and behavioral flexibility. Several lines of evidence indicate that oxytocin, signaling through its receptor (OXTR), is important in a wide range of social behaviors. In attempts to determine whether genetic variations in the oxytocin signaling system contribute to ASD susceptibility, seven recent reports indicated association of common genetic polymorphisms in the OXTR gene with ASD. Each involved relatively small sample sizes (57 to 436 families) and, where it was examined, failed to identify association of OXTR polymorphisms with measures of social behavior in individuals with ASD. We report genetic association analysis of 25 markers spanning the OXTR locus in 1,238 pedigrees including 2,333 individuals with ASD. Association of three markers previously implicated in ASD susceptibility, rs2268493 (P = 0.043), rs1042778 (P = 0.037), and rs7632287 (P = 0.016), was observed. Further, these genetic markers were associated with multiple core ASD phenotypes, including social domain dysfunction, measured by standardized instruments used to diagnose and describe ASD. The data suggest association of OXTR genetic polymorphisms with ASD, although the results should be interpreted with caution because none of the significant associations would survive appropriate correction for multiple comparisons. However, the current findings of association in a large independent cohort are consistent with previous results, and the biological plausibility of participation of the oxytocin signaling system in modulating social disruptions characteristic of ASD, suggest that functional polymorphisms of OXTR may contribute to ASD risk in a subset of families.

16. Campbell JM, Barger BD. {{Middle school students’ knowledge of autism}}. {J Autism Dev Disord};2011 (Jun);41(6):732-740.

Authors examined 1,015 middle school students’ knowledge of autism using a single item of prior awareness and a 10-item Knowledge of Autism (KOA) scale. The KOA scale was designed to assess students’ knowledge of the course, etiology, and symptoms associated with autism. Less than half of students (46.1%) reported having heard of autism; however, most students correctly responded that autism was a chronic condition that was not communicable. Students reporting prior awareness of autism scored higher on 9 of 10 KOA scale items when compared to their naive counterparts. Prior awareness of autism and KOA scores also differed across schools. A more detailed understanding of developmental changes in students’ knowledge of autism should improve peer educational interventions.

17. Chartan C, Aarons E, De A, Fishberger S, Messina J, Abdirahman I, Arora S, Dekna M, Lau KK. {{Index of Suspicion * Case 1: Status Epilepticus, Hypertension, and Tachycardia in a 5-year-old Boy * Case 2: Cardiopulmonary Arrest During Gymnastics Practice in a Teenage Girl * Case 3: Acute Renal Failure in a Teenage Boy Who Has Autism and Pica}}. {Pediatr Rev};2011 (Jun);32(6):257-263.

18. Chasson GS, Timpano KR, Greenberg JL, Shaw A, Singer T, Wilhelm S. {{Shared social competence impairment: another link between the obsessive-compulsive and autism spectrums?}}. {Clin Psychol Rev};2011 (Jun);31(4):653-662.

Recently, there has been a growing interest in the phenotypic, pathogenic, and pathophysiological overlap between autism spectrum disorders (ASD) and obsessive-compulsive spectrum disorders (OCSD). However, social competence impairment is one domain of overlap that has received less attention. Codified as one of three diagnostic categories in ASD, pathological social processing has also been demonstrated in OCSD. Yet, to date no reviews have synthesized the research literature on social competence impairments in OCSD, especially impairments that may parallel those found in ASD. The current review set out to examine the extant literature in this area in the service of advancing understanding of shared phenomenology between these two spectrums of conditions. Further, delineation of shared social competence impairments between ASD and OCSD might highlight candidate endophenotypes for further investigation. Ultimately, understanding the links between OCSD and ASD may aid in development of better intervention and prevention strategies, some of which may directly target maladaptive social processing.

19. Cheung AY, Horvath LM, Grafodatskaya D, Pasceri P, Weksberg R, Hotta A, Carrel L, Ellis J. {{Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation}}. {Hum Mol Genet};2011 (Jun 1);20(11):2103-2115.

Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder that affects girls due primarily to mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). The majority of RTT patients carry missense and nonsense mutations leading to a hypomorphic MECP2, while null mutations leading to the complete absence of a functional protein are rare. MECP2 is an X-linked gene subject to random X-chromosome inactivation resulting in mosaic expression of mutant MECP2. The lack of human brain tissue motivates the need for alternative human cellular models to study RTT. Here we report the characterization of a MECP2 mutation in a classic female RTT patient involving rearrangements that remove exons 3 and 4 creating a functionally null mutation. To generate human neuron models of RTT, we isolated human induced pluripotent stem (hiPS) cells from RTT patient fibroblasts. RTT-hiPS cells retained the MECP2 mutation, are pluripotent and fully reprogrammed, and retained an inactive X-chromosome in a nonrandom pattern. Taking advantage of the latter characteristic, we obtained a pair of isogenic wild-type and mutant MECP2 expressing RTT-hiPS cell lines that retained this MECP2 expression pattern upon differentiation into neurons. Phenotypic analysis of mutant RTT-hiPS cell-derived neurons demonstrated a reduction in soma size compared with the isogenic control RTT-hiPS cell-derived neurons from the same RTT patient. Analysis of isogenic control and mutant hiPS cell-derived neurons represents a promising source for understanding the pathogenesis of RTT and the role of MECP2 in human neurons.

20. Chiocchetti A, Pakalapati G, Duketis E, Wiemann S, Poustka A, Poustka F, Klauck SM. {{Mutation and expression analyses of the ribosomal protein gene RPL10 in an extended German sample of patients with autism spectrum disorder}}. {Am J Med Genet A};2011 (Jun);155(6):1472-1475.

21. Cohen JD, Nichols T, Brignone L, Hall SS, Reiss AL. {{Insular volume reduction in fragile X syndrome}}. {Int J Dev Neurosci};2011 (Jun);29(4):489-494.

Fragile X syndrome (FraX) is the most common form of inherited mental deficit and is caused by mutations of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome. While males and females with the full FMR1 mutation are affected differently because the disorder is X-linked, both suffer from varying degrees of cognitive impairment, attention deficits and social anxiety. The insula is a sensory integrative region that has been increasingly suggested as a critical area involved in anxiety manifestation. The current study was designed to examine possible changes in insular volume in FraX compared to age- and gender-matched typically developing healthy controls (HC) as well as age-, gender-, and intelligence-matched developmentally delayed controls (DD). An established native-space, manual morphometry method was utilized to quantify total and regional insular volumes using structural magnetic resonance imaging. Total, anterior and posterior insular volumes were found to be reduced in FraX compared to both HC and DD. The current data add to a growing literature concerning brain abnormalities in FraX and suggests that significant volume reduction of the insula is a component of the FraX neuroanatomical phenotype. This finding also provides an intriguing potential neural correlate for hyperarousal and gaze aversion, which are prominent behavioral symptoms of FraX.

22. Cukier HN, Salyakina D, Blankstein SF, Robinson JL, Sacharow S, Ma D, Wright HH, Abramson RK, Menon R, Williams SM, Haines JL, Cuccaro ML, Gilbert JR, Pericak-Vance MA. {{Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Jun);156(4):493-501.

Copy number variations (CNVs) play a crucial role in the intricate genetics of autism spectrum disorders. A region on chromosome 15q24 vulnerable to both deletions and duplications has been previously implicated in a range of phenotypes including autism, Asperger’s syndrome, delayed development, and mild to severe mental retardation. Prior studies have delineated a minimal critical region of approximately 1.33 Mb. In this study, a multiplex autism family was evaluated for CNVs using genotyping data from the Illumina 1 M BeadChip and analyzed with the PennCNV algorithm. Variants were then identified that co-segregate with autism features in this family. Here, we report autistic first cousins who carry two microduplications concordant with disease. Both duplications were inherited maternally and found to be identical by descent. The first is an approximately 10,000 base pair microduplication within the minimal region on 15q24 that falls across a single gene, ubiquitin-like 7. This is the smallest duplication in the region to result in a neuropsychiatric disorder, potentially narrowing the critical region for susceptibility to developmental and autism spectrum disorders. The second is a novel, 352 kb tandem duplication on 7p21 that replicates part of the neurexophilin 1 and islet cell autoantigen 1 genes. The breakpoint junction falls within the intronic regions of these genes and demonstrates a microhomology of four base pairs. Each of these microduplications may contribute to the complex etiology of autism spectrum disorders. (c) 2011 Wiley-Liss, Inc.

23. Curran MP. {{Aripiprazole: in the treatment of irritability associated with autistic disorder in pediatric patients}}. {Paediatr Drugs};2011 (Jun 1);13(3):197-204.

Aripiprazole is an atypical antipsychotic approved for the treatment of irritability associated with autistic disorder in pediatric patients aged 6-17 years. In two, randomized, double-blind, placebo-controlled studies in pediatric patients aged 6-17 years with irritability associated with autistic disorder, 8 weeks of treatment with aripiprazole 2-15 mg/day, compared with placebo, resulted in significant improvements in the Aberrant Behavior Checklist Irritability subscale score at endpoint (primary endpoint), and the mean Clinical Global Impression-Improvement score. Aripiprazole was generally well tolerated in this patient population in the two 8-week studies and a 52-week study, with most adverse events being mild to moderate in severity. Aripiprazole was associated with weight gain in both the short- and long-term studies; data from the long-term study indicated that the increase in bodyweight reached a plateau at 3-6 months.

24. Dewitt JC, Dietert RR. {{Response to « Theoretical aspects of autism: Causes-A review » by Ratajczak, HV (Journal of Immunotoxicology 8:68-79, 2011)}}. {J Immunotoxicol};2011 (May 31)

25. Fatemi SH, Folsom TD. {{The role of fragile X mental retardation protein in major mental disorders}}. {Neuropharmacology};2011 (Jun);60(7-8):1221-1226.

Fragile X mental retardation protein (FMRP) is highly enriched in neurons and binds to approximately 4% of mRNAs in mammalian brain. Its loss is a hallmark of fragile X syndrome (FXS), the most common form of mental retardation. In this review we discuss the mutation in the fragile X mental retardation-1 gene (FMR1), that leads to FXS, the role FMRP plays in neuronal cells, experiments from our own laboratory that demonstrate reductions of FMRP in additional psychiatric disorders (autism, schizophrenia, bipolar disorder, and major depressive disorder), and potential therapies to ameliorate the loss of FMRP. This article is part of a Special Issue entitled ‘Trends in neuropharmacology: in memory of Erminio Costa’.

26. Fountain C, King MD, Bearman PS. {{Age of diagnosis for autism: individual and community factors across 10 birth cohorts}}. {J Epidemiol Community Health};2011 (Jun);65(6):503-510.

Background The incidence of autism rose dramatically between 1992 and 2001, while the age at which children were first diagnosed declined. During this period the size and composition of the autism caseload has changed, but little is known about whether the factors associated with the timing of diagnosis may also have shifted. Using a multilevel analysis strategy, the individual and community-level factors associated with age of diagnosis were modelled across 10 birth cohorts of California children. Methods Linked birth and administrative records on 17 185 children with diagnoses of autistic disorder born in California between 1992 and 2001 and enrolled with the California Department of Developmental Services (DDS) were analysed. Information on cases, their parents and their residential location were extracted from birth and DDS records. Zip codes of residence were matched to census data to create community-level measures. Multilevel linear models were estimated for each birth cohort, with individual-level effects for sex, race, parental characteristics, poverty status, birth order and symptom expression. At the community level measures of educational and economic composition, local autism prevalence and the presence of a child psychiatrist were included. Results Children with highly educated parents are diagnosed earlier, and this effect has strengthened over time. There is a persistent gap in the age of diagnosis between high and low socioeconomic status (SES) children that has shrunk but not disappeared over time. Conclusion Routine screening for autism in early childhood for all children, particularly those of low SES, is necessary to eliminate disparities in early intervention.

27. Froehlich W. {{Making a case to continue considering treatment with selective serotonin reuptake inhibitors for children with autism spectrum disorders}}. {Curr Psychiatry Rep};2011 (Jun);13(3):170-173.

28. Geier DA, Kern JK, Davis G, King PG, Adams JB, Young JL, Geier MR. {{A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders}}. {Med Sci Monit};2011 (Jun 1);17(6):PI15-23.

Background: L-carnitine was proposed as a potential treatment for patients diagnosed with an autism spectrum disorder to improve mitochondrial dysfunction, but no prior randomized controlled trials have been conducted.<br /> Material/Methods: Thirty subjects diagnosed with an ASD were randomly assigned to receive a standardized regimen (50 mg L-carnitine/kg bodyweight/day) of liquid L-carnitine (n=19) or placebo (n=11) for 3-months. Measures included changes in professionally completed Childhood Autism Rating Scale (CARS), hand muscle testing, and modified clinical global impression (CGI) forms; parent completed Autism Treatment Evaluation Checklist (ATEC), treatment adherence measurement (TAM), frequency and intensity of side effect rating (FISER)/global rating of side effect burden (GRSEB)/patient report of incidence of side effects (PRISE) forms; and lab testing.<br /> Results: Significant improvements were observed in CARS (-2.03, 95% CI=-3.7 to -0.31), CGI (-0.69, 95% CI=-1.1 to -0.06), and ATEC scores. Significant correlations between changes in serum free-carnitine levels and positive clinical changes were observed for hand muscle strength (R2=0.23, P=0.046), cognitive scores (R2=0.27, P=0.019), and CARS scores (R2=0.20, P=0.047). Study subjects were protocol-compliant (average adherence was >85%) and generally well-tolerated the L-carnitine therapy given.<br /> Conclusions: L-carnitine therapy (50 mg/kilogram-bodyweight/day) administered for 3-months significantly improved several clinical measurements of ASD severity, but subsequent studies are recommended.<br />

29. Giannotti F, Cortesi F, Cerquiglini A, Vagnoni C, Valente D. {{Sleep in children with autism with and without autistic regression}}. {J Sleep Res};2011 (Jun);20(2):338-347.

The purpose of the present investigation was to characterize and compare traditional sleep architecture and non-rapid eye movement (NREM) sleep microstructure in a well-defined cohort of children with regressive and non-regressive autism, and in typically developing children (TD). We hypothesized that children with regressive autism would demonstrate a greater degree of sleep disruption either at a macrostructural or microstructural level and a more problematic sleep as reported by parents. Twenty-two children with non-regressive autism, 18 with regressive autism without comorbid pathologies and 12 with TD, aged 5-10 years, underwent standard overnight multi-channel polysomnographic evaluation. Parents completed a structured questionnaire (Childrens’ Sleep Habits Questionnaire-CSHQ). The initial hypothesis, that regressed children have more disrupted sleep, was supported by our findings that they scored significantly higher on CSHQ, particularly on bedtime resistance, sleep onset delay, sleep duration and night wakings CSHQ subdomains than non-regressed peers, and both scored more than typically developing controls. Regressive subjects had significantly less efficient sleep, less total sleep time, prolonged sleep latency, prolonged REM latency and more time awake after sleep onset than non-regressive children and the TD group. Regressive children showed lower cyclic alternating pattern (CAP) rates and A1 index in light sleep than non-regressive and TD children. Our findings suggest that, even though no particular differences in sleep architecture were found between the two groups of children with autism, those who experienced regression showed more sleep disorders and a disruption of sleep either from a macro- or from a microstructural viewpoint.

30. Gjevik E, Eldevik S, Fjaeran-Granum T, Sponheim E. {{Kiddie-SADS Reveals High Rates of DSM-IV Disorders in Children and Adolescents with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (Jun);41(6):761-769.

Prevalence of current comorbid DSM-IV disorders was assessed in a special school population of children and adolescents with ASD (N = 71, age 6.0-17.9 years), representing all cognitive levels and main ASD subgroups. Symptoms were assessed through parent interview and association to child characteristics was explored. Seventy-two percent was diagnosed with at least one comorbid disorder. Anxiety disorders (41%) and attention deficit/hyperactivity disorder (31%) were most prevalent. Obsessive-compulsive disorder was more common in older children, and oppositional defiant disorder/conduct disorder more prevalent in pervasive developmental disorder, not otherwise specified. Our results show high rates of comorbid DSM-IV disorders and underscore the importance of such evaluation in children ASD. However, diagnostic challenges are present and future research on the diagnostic validity of comorbid psychiatric disorders is needed.

31. Gomot M, Blanc R, Clery H, Roux S, Barthelemy C, Bruneau N. {{Candidate electrophysiological endophenotypes of hyper-reactivity to change in autism}}. {J Autism Dev Disord};2011 (Jun);41(6):705-714.

Although resistance to change is a main feature of autism, the brain processes underlying this aspect of the disorder remain poorly understood. The aims of this study were to examine neural basis of auditory change-detection in children with autism spectrum disorders (ASD; N = 27) through electrophysiological patterns (MMN, P3a) and to test whether these are quantitatively related to intolerance of change (using the BSE-R scale). ASD displayed significantly shorter MMN latency and larger P3a than controls, indicating a greater tendency to switch attention to deviant events. These electrophysiological abnormalities were significantly more marked in children who displayed greater difficulties in tolerating change. The atypical neurophysiological mechanism of change perception identified might thus be associated with one of the hallmark behavioural manifestations of autism.

32. Hagebeuk EE, Koelman JH, Duran M, Abeling NG, Vyth A, Poll-The BT. {{Clinical and electroencephalographic effects of folinic Acid treatment in rett syndrome patients}}. {J Child Neurol};2011 (Jun);26(6):718-723.

Rett syndrome is characterized by the development of stereotypic hand movements and seizures, which are often difficult to treat. Previous studies have shown conflicting results during add-on folinic acid. Here, the authors reevaluate the response to folinic acid in terms of epilepsy control and electroencephalography features. They performed a randomized, placebo-controlled, double-blind crossover trial, with a follow-up of more than 2 years. Twelve girls with Rett syndrome participated, comparable in clinical stage and disease severity. The Rett syndrome patients were given either folinic acid or placebo, for 1 year each. Only 3 girls benefited to some extent: 2 had a reduction and/or decrease in seizures, and all 3 showed some decreased epileptiform activity on electroencephalography during the addition of folinic acid. Despite this, antiepileptic drugs were adjusted. Because the effect of added folinic acid was limited and did not prevent antiepileptic drug increase, the authors do not recommend adding on folinic acid in Rett syndrome girls with epilepsy.

33. Happe F. {{Criteria, Categories, and Continua: Autism and Related Disorders in DSM-5}}. {J Am Acad Child Adolesc Psychiatry};2011 (Jun);50(6):540-542.

34. Hodgetts S, Magill-Evans J, Misiaszek JE. {{Weighted vests, stereotyped behaviors and arousal in children with autism}}. {J Autism Dev Disord};2011 (Jun);41(6):805-814.

The homeostatic theory of stereotyped behaviors assumes that these behaviors modulate arousal. Weighted vests are used to decrease stereotyped behaviors in persons with autism because the input they provide is thought to serve the same homeostatic function. This small-n, randomized and blinded study measured the effects of wearing a weighted vest on stereotyped behaviors and heart rate for six children with autism in the classroom. Weighted vests did not decrease motoric stereotyped behaviors in any participant. Verbal stereotyped behaviors decreased in one participant. Weighted vests did not decrease heart rate. Heart rate increased in one participant. Based on this protocol, the use of weighted vests to decrease stereotyped behaviors or arousal in children with autism in the classroom was not supported.

35. Holdnack J, Goldstein G, Drozdick L. {{Social Perception and WAIS-IV Performance in Adolescents and Adults Diagnosed With Asperger’s Syndrome and Autism}}. {Assessment};2011 (Jun);18(2):192-200.

Previous research using the Wechsler scales has identified areas of cognitive weaknesses in children, adolescents, and adults diagnosed with Autism or Asperger’s syndrome. The current study evaluates cognitive functioning in adolescents and adults diagnosed with Autism or Asperger’s syndrome using the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and the Social Perception subtest from the Advanced Clinical Solutions. Deficits in social perception, verbal comprehension, and processing speed were found in the Autism sample. Additionally, they exhibited inconsistent performance on auditory working memory and perceptual reasoning tasks. The Asperger’s syndrome group had better overall cognitive skills than the Autism group, but compared with controls, they had weaknesses in processing speed, social perception, and components of auditory working memory. Both groups had relatively low scores on the WAIS-IV Comprehension subtest compared with the other verbal comprehension subtests. Clinical application and utility of the WAIS-IV and Social Perception in Autism Spectrum Disorders are discussed.

36. Hunsaker MR, Greco CM, Tassone F, Berman RF, Willemsen R, Hagerman RJ, Hagerman PJ. {{Rare Intranuclear Inclusions in the Brains of 3 Older Adult Males With Fragile X Syndrome: Implications for the Spectrum of Fragile X-Associated Disorders}}. {J Neuropathol Exp Neurol};2011 (Jun);70(6):462-469.

The FMR1 gene is polymorphic for the length of CGG trinucleotide repeat expansions in the 5′ untranslated region. Premutation (55-200 CGG repeats) and full-mutation (>200 CGG repeats) alleles give rise to their respective disorders by different pathogenic mechanisms: RNA gain-of-function toxicity leads to fragile X-associated tremor/ataxia syndrome in the premutation range, and transcriptional silencing and absence of fragile X mental retardation protein (FMRP) lead to fragile X syndrome in the full-mutation range. However, for the latter, incomplete silencing and/or size-mosaicism might result insome contribution to the disease process from residual messenger RNA production. To address this possibility, we examined the brains of 3 cases of fragile X syndrome for the presence of intranuclear inclusions in the hippocampal dentate gyrus. We identified low levels (0.1%-1.3%) of intranuclear inclusions in all 3 cases. Quantitative reverse transcription-polymerase chain reaction for FMR1 messenger RNA and immunofluorescence for FMRP revealed low but detectable levels of both RNA and protein in the 3 cases, consistent with the presence of small numbers of inclusions. The intranuclear inclusions were only present in FMRP-immunoreactive cells. The small numbers of inclusions and very low levels of both FMR1 RNA and protein suggest that the clinical course in these 3 subjects would not have been influenced by contributions from RNA toxicity.

37. Hvidtjorn D, Grove J, Schendel D, Schieve LA, Svaerke C, Ernst E, Thorsen P. {{Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study}}. {J Epidemiol Community Health};2011 (Jun);65(6):497-502.

Objectives To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. Design Population-based follow-up study. Setting All children born alive in Denmark 1995-2003. Participants 588 967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. Main outcome measures A diagnosis of ASD in the Danish Psychiatric Central Register. Results 33 139 (5.6%) of all children born in Denmark in 1995-2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555 828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4-13&emsp14;years (median 9&emsp14;years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. Discussion This population-based follow-up study found no risk of ASD in children born after assisted conception.

38. Jaber MA. {{Dental caries experience, oral health status and treatment needs of dental patients with autism}}. {J Appl Oral Sci};2011 (Jun);19(3):212-217.

OBJECTIVES: Autism is a lifelong neurodevelopmental disorder. The aims of this study were to investigate whether children with autism have higher caries prevalence, higher periodontal problems, or more treatment needs than children of a control group of non-autistic patients, and to provide baseline data to enable comparison and future planning of dental services to autistic children. MATERIAL AND METHODS: 61 patients with autism aged 6-16 years (45 males and 16 females) attending Dubai and Sharjah Autism Centers were selected for the study. The control group consisted of 61 non-autistic patients chosen from relatives or friends of autistic patients in an attempt to have matched age, sex and socioeconomic status. Each patient received a complete oral and periodontal examination, assessment of caries prevalence, and caries severity. Other conditions assessed were dental plaque, gingivitis, restorations and treatment needs. Chi-square and Fisher’s exact test of significance were used to compare groups. RESULTS: The autism group had a male-to-female ratio of 2.8:1. Compared to controls, children with autism had significantly higher decayed, missing or filled teeth than unaffected patients and significantly needed more restorative dental treatment. The restorative index (RI) and Met Need Index (MNI) for the autistic children were 0.02 and 0.3, respectively. The majority of the autistic children either having poor 59.0% (36/61) or fair 37.8% (23/61) oral hygiene compared with healthy control subjects. Likewise, 97.0% (59/61) of the autistic children had gingivitis. CONCLUSIONS: Children with autism exhibited a higher caries prevalence, poor oral hygiene and extensive unmet needs for dental treatment than non-autistic healthy control group. Thus oral health program that emphasizes prevention should be considered of particular importance for children and young people with autism.

39. Johnston-Macananny EB, Koty P, Pettenati M, Brady M, Yalcinkaya TM, Schmidt DW. {{The first case described: monozygotic twin sisters with the fragile X premutation but with a different phenotype for premature ovarian failure}}. {Fertil Steril};2011 (Jun);95(7):2431 e2413-2435.

OBJECTIVE: To describe the first case of monozygotic twin sisters with fragile X premutation and discordance for premature ovarian failure (POF). DESIGN: A descriptive case study. SETTING: Academic center. PATIENT(S): Monozygotic twin sisters with fragile X premutation and discordance for POF. INTERVENTION(S): Serum laboratory testing, fragile X premutation screening, zygosity testing, X-inactivation ratio and Southern blot studies. MAIN OUTCOME MEASURE(S): Incidence of POF in this twin cohort. RESULT(S): Zygosity analysis using polymerase chain reaction of 15 polymorphic markers via capillary gel electrophoresis in these patients confirmed their monozygosity. X-inactivation studies were performed using the human androgen receptor (HUMARA) gene and revealed similar X-inactivation ratios for both the patient and her sister (11:89 and 12:88, respectively) from peripheral serum samples. Southern blot evaluation of the proband and her sister revealed a similar methylation pattern in which the premutation allele was unmethylated much more than the normal allele. The contribution of the premutation on the active allele as determined by Southern blot analysis was consistent between sisters. CONCLUSION(S): The inactivation ratio studies and subsequent Southern blot analysis do not show differences between the patients; therefore, we are unable to identify a causative mechanism for the identical sisters’ discordant phenotypes. It is possible that the inactivation ratios observed from the peripheral blood specimens obtained from the sisters do not represent the allele expression and skewing present at the level of the ovary.

40. Kaluzna-Czaplinska J. {{Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children}}. {Clin Biochem};2011 (Jun);44(8-9):686-691.

OBJECTIVES: Quantitative organic acid testing can give information about potential problems, especially with energy production, neurotransmitter metabolism, intestinal dysbiosis and nutritional individuality which is very important in autistic children. The aim of this study was to find out potential differences between the levels of organic acids in the urine of autistic and non-autistic children. DESIGN AND METHODS: The organic acids in the urine were determined by capillary gas chromatography/mass spectrometry (GC/MS). All overnight urine samples were collected from 35 autistic children and 36 neurologically normal children as healthy controls (4-10years). RESULTS: Significant differences were found between the autistic children and the control group in organic acids: 2-oxoglutaric, isocitric, citric, 4-hydroxybenzoic, 4-hydroxyphenylacetic, hippuric, adipic, suberic (all with p<0.05). CONCLUSION: Organic acids test can be used to assess an individual need for nutrient and biochemical abnormalities, especially important for autistic children.

41. Kita Y, Gunji A, Inoue Y, Goto T, Sakihara K, Kaga M, Inagaki M, Hosokawa T. {{Self-face recognition in children with autism spectrum disorders: A near-infrared spectroscopy study}}. {Brain Dev};2011 (Jun);33(6):494-503.

It is assumed that children with autism spectrum disorders (ASD) have specificities for self-face recognition, which is known to be a basic cognitive ability for social development. In the present study, we investigated neurological substrates and potentially influential factors for self-face recognition of ASD patients using near-infrared spectroscopy (NIRS). The subjects were 11 healthy adult men, 13 normally developing boys, and 10 boys with ASD. Their hemodynamic activities in the frontal area and their scanning strategies (eye-movement) were examined during self-face recognition. Other factors such as ASD severities and self-consciousness were also evaluated by parents and patients, respectively. Oxygenated hemoglobin levels were higher in the regions corresponding to the right inferior frontal gyrus than in those corresponding to the left inferior frontal gyrus. In two groups of children these activities reflected ASD severities, such that the more serious ASD characteristics corresponded with lower activity levels. Moreover, higher levels of public self-consciousness intensified the activities, which were not influenced by the scanning strategies. These findings suggest that dysfunction in the right inferior frontal gyrus areas responsible for self-face recognition is one of the crucial neural substrates underlying ASD characteristics, which could potentially be used to evaluate psychological aspects such as public self-consciousness.

42. Krebs JF, Biswas A, Pascalis O, Kamp-Becker I, Remschmidt H, Schwarzer G. {{Face processing in children with autism spectrum disorder: independent or interactive processing of facial identity and facial expression?}}. {J Autism Dev Disord};2011 (Jun);41(6):796-804.

The current study investigated if deficits in processing emotional expression affect facial identity processing and vice versa in children with autism spectrum disorder. Children with autism and IQ and age matched typically developing children classified faces either by emotional expression, thereby ignoring facial identity or by facial identity disregarding emotional expression. Typically developing children processed facial identity independently from facial expressions but processed facial expressions in interaction with identity. Children with autism processed both facial expression and identity independently of each other. They selectively directed their attention to one facial parameter despite variations in the other. Results indicate that there is no interaction in processing facial identity and emotional expression in autism spectrum disorder.

43. Lane AE, Dennis SJ, Geraghty ME. {{Brief report: further evidence of sensory subtypes in autism}}. {J Autism Dev Disord};2011 (Jun);41(6):826-831.

Distinct sensory processing (SP) subtypes in autism have been reported previously. This study sought to replicate the previous findings in an independent sample of thirty children diagnosed with an Autism Spectrum Disorder. Model-based cluster analysis of parent-reported sensory functioning (measured using the Short Sensory Profile) confirmed the triad of sensory subtypes reported earlier. Subtypes were differentiated from each other based on degree of SP dysfunction, taste/smell sensitivity and vestibular/proprioceptive processing. Further elucidation of two of the subtypes was also achieved in this study. Children with a primary pattern of sensory-based inattention could be further described as sensory seekers or non-seekers. Children with a primary pattern of vestibular/proprioceptive dysfunction were also differentiated on movement and tactile sensitivity.

44. Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, Song C, Buijsen RA, Pop AS, Gomezmancilla B, Nelson DL, Willemsen R, Gasparini F, Oostra BA. {{AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome}}. {Neurobiol Dis};2011 (Jun);42(3):311-317.

Fragile X syndrome, the most common form of inherited intellectual disability, is caused by a lack of FMRP, which is the product of the Fmr1 gene. FMRP is an RNA-binding protein and a component of RNA-granules found in the dendrites of neurons. At the synapse, FMRP is involved in regulation of translation of specific target mRNAs upon stimulation of mGluR5 receptors. In this study, we test the effects of a new mGluR5 antagonist (AFQ056) on the prepulse inhibition of startle response in mice. We show that Fmr1 KO mice have a deficit in inhibition of the startle response after a prepulse and that AFQ056 can rescue this phenotype. We also studied the effect of AFQ056 on cultured Fmr1 KO hippocampal neurons; untreated neurons showed elongated spines and treatment resulted in shortened spines. These results suggest that AFQ056 might be a potent mGluR5 antagonist to rescue various aspects of the fragile X phenotype.

45. Lin LY. {{Factors associated with caregiving burden and maternal pessimism in mothers of adolescents with an autism spectrum disorder in Taiwan}}. {Occup Ther Int};2011 (Jun);18(2):96-105.

Relative to the United States and other western countries, less research has focused on factors associated with caregiving burden and maternal pessimism in Taiwanese mothers of adolescents with an autism spectrum disorder (ASD). The characteristics of 50 adolescents with an ASD living at home in Taiwan and its association with caregiving burden and maternal pessimism were examined. The age range of adolescents with an ASD was from 10 to 18. Mothers, aged 35 to 55 years, completed self-report written questionnaires regarding their child’s adaptive functioning and their own perceptions of caregiving burdens and concerns. Findings indicated that functional independence, severe maladaptive behaviours and severity of autism were predictive of maternal caregiving burden. Maternal pessimism was associated with functional independence and severity of autism. The findings of this study indicated that occupational therapy practitioners could focus on training functional independence of the individual with an ASD to meet the family’s need in Taiwan. Researchers should pay significant attention to the lifespan issues of autism in Taiwanese families. The major limitations of this study were small sample size and without a comparison group. Future research using larger samples with a comparison group is needed. Copyright (c) 2010 John Wiley & Sons, Ltd.

46. Liu Y, Cherkassky VL, Minshew NJ, Just MA. {{Autonomy of lower-level perception from global processing in autism: Evidence from brain activation and functional connectivity}}. {Neuropsychologia};2011 (Jun);49(7):2105-2111.

Previous behavioral studies have shown that individuals with autism are less hindered by interference from global processing during the performance of lower-level perceptual tasks, such as finding embedded figures. The primary goal of this study was to examine the brain manifestation of such atypicality in high-functioning autism using fMRI. Fifteen participants with high-functioning autism and fifteen age- and IQ-matched typical controls were asked to perform a lower-level perceptual line-counting task in the presence of a distracting depiction of a 3-D object, in which participants counted whether there were more red or more green contours (In a contrasting 3-D task, participants judged whether the same 3-D stimulus objects (but without color in any contours) depicted a possible or impossible 3-D object). We hypothesized that individuals with autism would be less likely than controls to process the global 3-D information (and would hence show fewer neural signs of such interfering 3-D processing) during the lower-level line-counting task. The fMRI results revealed that in the line-counting task, the autism group did not show the increased medial frontal activity (relative to the possibility task), or the increased functional connectivity between the medial frontal region and posterior visual-spatial regions, demonstrated by the control group. Both findings are indices of lesser effort and difficulty in the line-counting task for the autism group than for the control group, attributed to less interference from the 3-D processing in the autism group. In addition, in the line-counting task, the control group showed a positive correlation between a measure of spatial ability (Vandenberg scores) and activation in the medial frontal region, suggesting that more spatially able control participants did more suppression of the irrelevant 3-D background information in order to focus on the line-counting task. The findings collectively indicate that the global 3-D structure of the figure had a smaller effect, if any, on local processing in the group with autism compared to the control group. The results from this study provide the first direct neural evidence of reduced global-to-local interference in autism.

47. Liu ZH, Chuang DM, Smith CB. {{Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome}}. {Int J Neuropsychopharmacol};2011 (Jun);14(5):618-630.

As our understanding of the underlying defects in fragile X syndrome (FXS) increases so does the potential for development of treatments aimed at modulating the defects and ameliorating the constellation of symptoms seen in patients. Symptoms of FXS include cognitive disability, hyperactivity, autistic behaviour, seizures and learning deficits. Lithium is a drug used clinically to treat bipolar disorder, and it has been used to treat mood dysregulation in individuals with FXS. We examined whether dietary lithium would alter behavioural and morphological abnormalities in fmr1 knockout (KO) mice. We studied wild-type (WT) and KO mice untreated (control chow) or treated with lithium (0.3% lithium-carbonate-containing chow) commenced at weaning and maintained throughout the experiment. At age 8-12 wk, mice were subjected to the following behavioural tests: open field, social interaction, elevated plus maze, elevated zero maze and passive avoidance. At 13 wk, brains were prepared for Golgi staining and analysis of dendritic spine morphology in medial prefrontal cortex. We found that compared to untreated WT, untreated KO mice were hyperactive and had reduced anxiety, impaired social interactions, and deficits on a learning test. Dendritic spines in medial prefrontal cortex were longer and increased in number. Lithium treatment ameliorated the hyperactivity and reversed impaired social interaction and deficits on the learning test. Lithium treatment also partially normalized general anxiety levels and dendritic spine morphology. Our findings and those from other laboratories on the efficacy of lithium treatment in animal models support further studies in patients with FXS.

48. Lombardo MV, Chakrabarti B, Bullmore ET, Baron-Cohen S. {{Specialization of right temporo-parietal junction for mentalizing and its relation to social impairments in autism}}. {Neuroimage};2011 (Jun 1);56(3):1832-1838.

Over the last 25years, « mindblindness » (deficits in representing mental states) has been one of the primary explanations behind the hallmark social-communication difficulties in autism spectrum conditions (ASC). However, highlighting neural systems responsible for mindblindness and their relation to variation in social impairments has remained elusive. In this study we show that one of the neural systems responsible for mindblindness in ASC and its relation to social impairments is the right temporo-parietal junction (RTPJ). Twenty-nine adult males with ASC and 33 age and IQ-matched Controls were scanned with fMRI while making reflective mentalizing or physical judgments about themselves or another person. Regions of interest within mentalizing circuitry were examined for between-group differences in activation during mentalizing about self and other and correlations with social symptom severity. RTPJ was the only mentalizing region that responded atypically in ASC. In Controls, RTPJ was selectively more responsive to mentalizing than physical judgments. This selectivity for mentalizing was not apparent in ASC and generalized across both self and other. Selectivity of RTPJ for mentalizing was also associated with the degree of reciprocal social impairment in ASC. These results lend support to the idea that RTPJ is one important neural system behind mindblindness in ASC. Understanding the contribution of RTPJ in conjunction with other neural systems responsible for other component processes involved in social cognition will be illuminating in fully explaining the hallmark social-communication difficulties of autism.

49. Manning SE, Davin CA, Barfield WD, Kotelchuck M, Clements K, Diop H, Osbahr T, Smith LA. {{Early diagnoses of autism spectrum disorders in massachusetts birth cohorts, 2001-2005}}. {Pediatrics};2011 (Jun);127(6):1043-1051.

OBJECTIVE: We examined trends in autism spectrum disorder diagnoses by age 36 months (early diagnoses) and identified characteristics associated with early diagnoses. METHODS: Massachusetts birth certificate and early-intervention program data were linked to identify infants born between 2001 and 2005 who were enrolled in early intervention and receiving autism-related services before age 36 months (through December 31, 2008). Trends in early autism spectrum disorders were examined using Cochran-Armitage trend tests. chi(2) Statistics were used to compare distributions of selected characteristics for children with and without autism spectrum disorders. Multivariate logistic regression analyses were conducted to identify independent predictors of early diagnoses. RESULTS: A total of 3013 children (77.5 per 10 000 study population births) were enrolled in early intervention for autism spectrum disorder by age 36 months. Autism spectrum disorder incidence increased from 56 per 10 000 infants among the 2001 birth cohort to 93 per 10 000 infants in 2005. Infants of mothers younger than 24 years of age, whose primary language was not English or who were foreign-born had lower odds of an early autism spectrum disorder diagnosis. Maternal age older than 30 years was associated with increased odds of an early autism spectrum disorder diagnosis. Odds of early autism spectrum disorders were 4.5 (95% confidence interval: 4.1-5.0) times higher for boys than girls. CONCLUSIONS: Early autism spectrum disorder diagnoses are increasing in Massachusetts, reflecting the national trend observed among older children. Linkage of early-intervention program data with population-based vital statistics is valuable for monitoring autism spectrum disorder trends and planning developmental and educational service needs.

50. Maras K, Bowler DM. {{Brief report: schema consistent misinformation effects in eyewitnesses with autism spectrum disorder}}. {J Autism Dev Disord};2011 (Jun);41(6):815-820.

A number of studies have demonstrated schema-related misinformation effects in typical individuals, but no research to date has examined this with witnesses with autism spectrum disorder (ASD), despite their impaired ability to generate core elements that define everyday events. After witnessing slides depicting a bank robbery, 16 adults with ASD and 16 matched comparison individuals were exposed to post-event misinformation that was either schema typical or atypical. Consistent with previous work, the comparison group went onto report more schema typical misinformatio