1. Blankenship K, Erickson CA, Stigler KA, Posey DJ, McDougle CJ. {{Aripiprazole for irritability associated with autistic disorder in children and adolescents aged 6-17 years}}. {Ped Health};2010 (Sep 29);4(4):375-381.

Aripiprazole was recently US FDA-approved to treat irritability in children and adolescents with autistic disorder aged 6-17 years. There are currently only two psychotropics approved by the FDA to treat irritability in the autistic population. This drug profile will discuss available studies of aripiprazole in individuals with pervasive developmental disorders, two of which led to its recent FDA approval. We will discuss the efficacy, as well as the safety and tolerability of the drug documented in these studies. In addition, the chemistry, pharmacokinetics, metabolism and mechanism of action of aripiprazole will be reviewed.

2. Buxbaum JD, Hof PR. {{The emerging neuroscience of autism spectrum disorders}}. {Brain Res};2011 (Mar 22);1380:1-2.

3. Charania SM, Leblanc LA, Sabanathan N, Ktaech IA, Carr JE, Gunby K. {{Teaching effective hand raising to children with autism during group instruction}}. {J Appl Behav Anal};2010 (Fall);43(3):493-497.

We taught 3 children with autism to raise a hand or keep both hands down depending on their status (e.g., having heard a target word, possessing a specific item) using modeling, prompting, and reinforcement. All 3 children acquired accurate hand-raising skills in response to progressively more difficult discrimination tasks during group instruction. The implications for preparing children for general education settings are discussed.

4. Doyen C, Mighiu D, Kaye K, Colineaux C, Beaumanoir C, Mouraeff Y, Rieu C, Paubel P, Contejean Y. {{Melatonin in children with autistic spectrum disorders: recent and practical data}}. {Eur Child Adolesc Psychiatry};2011 (Feb 26)

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

5. Gai X, Xie HM, Perin JC, Takahashi N, Murphy K, Wenocur AS, D’Arcy M, O’Hara RJ, Goldmuntz E, Grice DE, Shaikh TH, Hakonarson H, Buxbaum JD, Elia J, White PS. {{Rare structural variation of synapse and neurotransmission genes in autism}}. {Mol Psychiatry};2011 (Mar 1)

Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci.Molecular Psychiatry advance online publication, 1 March 2011; doi:10.1038/mp.2011.10.

6. Griswold AJ, Ma D, Sacharow SJ, Robinson JL, Jaworski JM, Wright HH, Abramson RK, Lybaek H, Oyen N, Cuccaro ML, Gilbert JR, Pericak-Vance MA. {{A de Novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis}}. {Autism Res};2011 (Feb 28)

Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5-7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk.

7. Hernandez P, Ikkanda Z. {{Applied behavior analysis: Behavior management of children with autism spectrum disorders in dental environments}}. {J Am Dent Assoc};2011 (Mar);142(3):281-287.

BACKGROUND: There are a limited number of studies addressing behavior management techniques and procedural modifications that dentists can use to treat people with an autism spectrum disorder (ASD). METHODS: The authors conducted a search of the dental and behavioral analytic literature to identify management techniques that address problem behaviors exhibited by children with ASDs in dental and other health-related environments. RESULTS: Applied behavior analysis (ABA) is a science in which procedures are based on the principles of behavior through systematic experimentation. Clinicians have used ABA procedures successfully to modify socially significant behaviors of people with ASD. Basic behavior management techniques currently used in dentistry may not encourage people with cognitive and behavioral disabilities, such as ASD, to tolerate simple in-office dental procedures consistently. Instead, dental care providers often are required to use advanced behavior management techniques to complete simple in-office procedures such as prophylaxis, sealant placement and obtaining radiographs. ABA procedures can be integrated in the dental environment to manage problem behaviors often exhibited by children with an ASD. CONCLUSIONS: The authors found no evidence-based procedural modifications that address the behavioral characteristics and problematic behaviors of children with an ASD in a dental environment. Further research in this area should be conducted. CLINICAL IMPLICATIONS: Knowledge and in-depth understanding of behavioral principles is essential when a dentist is concerned with modifying behaviors. Using ABA procedures can help dentists manage problem behaviors effectively and systematically when performing routine dental treatment. Being knowledgeable about each patient’s behavioral characteristics and the parents’ level of involvement is important in the successful integration of the procedures and reduction of in-office time.

8. Lee H, Kang HC, Kim SW, Kim YK, Chung HJ. {{Characteristics of late-onset epilepsy and EEG findings in children with autism spectrum disorders}}. {Korean J Pediatr};2011 (Jan);54(1):22-28.

PURPOSE: To investigate the clinical characteristics of late-onset epilepsy combined with autism spectrum disorder (ASD), and the relationship between certain types of electroencephalography (EEG) abnormalities in ASD and associated neuropsychological problems. METHODS: Thirty patients diagnosed with ASD in early childhood and later developed clinical seizures were reviewed retrospectively. First, the clinical characteristics, language and behavioral regression, and EEG findings of these late-onset epilepsy patients with ASD were investigated. The patients were then classified into 2 groups according to the severity of the EEG abnormalities in the background rhythm and paroxysmal discharges. In the severe group, EEG showed persistent asymmetry, slow and disorganized background rhythms, and continuous sharp and slow waves during slow sleep (CSWS). RESULTS: Between the two groups, there was no statistically significant difference in mean age (P=0.259), age of epilepsy diagnosis (P=0.237), associated family history (P=0.074), and positive abnormal magnetic resonance image (MRI) findings (P=0.084). The severe EEG group tended to have more neuropsychological problems (P=0.074). The severe group statistically showed more electrographic seizures in EEG (P=0.000). Rett syndrome was correlated with more severe EEG abnormalities (P=0.002). Although formal cognitive function tests were not performed, the parents reported an improvement in neuropsychological function on the follow up checkup according to a parent’s questionnaire. CONCLUSION: Although some ASD patients with late-onset epilepsy showed severe EEG abnormalities, including CSWS, they generally showed an improvement in EEG and clinical symptoms in the long-term follow up. In addition, severe EEG abnormalities tended to be related to the neuropsychological function.

9. 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 (Feb 25)

Over the last 25 years, ‘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.

10. Mathewson KJ, Drmic IE, Jetha MK, Bryson SE, Goldberg JO, Hall GB, Santesso DL, Segalowitz SJ, Schmidt LA. {{Behavioral and cardiac responses to emotional stroop in adults with autism spectrum disorders: influence of medication}}. {Autism Res};2011 (Feb 28)

Researchers have recently hypothesized that autism spectrum disorders (ASD) may be partly characterized by physiological over-arousal. One way to assess physiological arousal is through autonomic measures. Here heart period (HP) and parasympathetic activity measured by respiratory sinus arrhythmia (RSA) were examined in adults with ASD and matched controls at rest and during performance of an emotional Stroop task. Resting HP and RSA were lower in adults with ASD than in matched controls, consistent with hypothesized over-arousal in ASD. However, dividing the ASD group on the basis of antipsychotic medication usage revealed that group differences in autonomic arousal may be related to the effects of these medications or their correlates. Autonomic adjustments for Stroop performance were comparable across groups, but in the control group, larger RSA reductions were correlated with faster responding (i.e., better performance). This relation was reversed in the unmedicated ASD group and absent in the medicated ASD group. Findings highlight the importance of considering medication status in the recently burgeoning area of psychophysiological studies of autism.

11. Miles JH. {{Autism spectrum disorders-A genetics review}}. {Genet Med};2011 (Feb 24)

Autism is an etiologically and clinically heterogeneous group of disorders, diagnosed solely by the complex behavioral phenotype. On the basis of the high-heritability index, geneticists are confident that autism will be the first behavioral disorder for which the genetic basis can be well established. Although it was initially assumed that major genome-wide and candidate gene association studies would lead most directly to common autism genes, progress has been slow. Rather, most discoveries have come from studies of known genetic disorders associated with the behavioral phenotype. New technology, especially array chromosomal genomic hybridization, has both increased the identification of putative autism genes and raised to approximately 25%, the percentage of children for whom an autism-related genetic change can be identified. Incorporating clinical geneticists into the diagnostic and autism research arenas is vital to the field. Interpreting this new technology and deciphering autism’s genetic montage require the skill set of the clinical geneticist including knowing how to acquire and interpret family pedigrees, how to analyze complex morphologic, neurologic, and medical phenotypes, sorting out heterogeneity, developing rational genetic models, and designing studies. The current emphasis on deciphering autism spectrum disorders has accelerated the field of neuroscience and demonstrated the necessity of multidisciplinary research that must include clinical geneticists both in the clinics and in the design and implementation of basic, clinical, and translational research.

12. Murphy C, Barnes-Holmes D. {{Establishing five derived mands in three adolescent boys with autism}}. {J Appl Behav Anal};2010 (Fall);43(3):537-541.

Three 14-year-old boys with diagnoses of autism learned to mand for the delivery or removal of tokens by presenting nonsense syllables (A(1-5), respectively). A match-to-sample procedure was used to establish conditional discriminations between the 5 A stimuli and 5 B stimuli and between the B stimuli and 5 C stimuli. Subsequently, each participant was able to use the C stimuli to mand, illustrating a transfer of function, although 1 participant first required multiple-exemplar training.

13. Oblak AL, Rosene DL, Kemper TL, Bauman ML, Blatt GJ. {{Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism}}. {Autism Res};2011 (Feb 28)

Autism is a developmental disorder with prenatal origins, currently estimated to affect 1 in 91 children in the United States. Social-emotional deficits are a hallmark of autism and early neuropathology studies have indicated involvement of the limbic system. Imaging studies demonstrate abnormal activation of the posterior cingulate cortex (PCC), a component of the limbic system. Abnormal activation has also been noted in the fusiform gyrus (FFG), a region important for facial recognition and a key element in social interaction. A potential imbalance between excitatory and inhibitory interneurons in the cortex may contribute to altered information processing in autism. Furthermore, reduced numbers of GABA receptors have previously been reported in the autistic brain. Thionin-stained sections were used to qualitatively assess cytoarchitectonic patterning and quantitatively determine the density of neurons and immunohistochemistry was used to determine the densities of a subset of GABAergic interneurons utilizing parvalbumin-and calbindin-immunoreactivity. In autism, the PCC displayed altered cytoarchitecture with irregularly distributed neurons, poorly demarcated layers IV and V, and increased presence of white matter neurons. In contrast, no neuropathology was observed in the FFG. There was no significant difference in the density of thionin, parvalbumin, or calbindin interneurons in either region and there was a trend towards a reduced density of calbindin neurons in the PCC. This study highlights the presence of abnormal findings in the PCC, which appear to be developmental in nature and could affect the local processing of social-emotional behaviors as well as functioning of interrelated areas.

14. Sarachana T, Xu M, Wu RC, Hu VW. {{Sex Hormones in Autism: Androgens and Estrogens Differentially and Reciprocally Regulate RORA, a Novel Candidate Gene for Autism}}. {PLoS One};2011;6(2):e17116.

Autism, a pervasive neurodevelopmental disorder manifested by deficits in social behavior and interpersonal communication, and by stereotyped, repetitive behaviors, is inexplicably biased towards males by a ratio of approximately 4ratio1, with no clear understanding of whether or how the sex hormones may play a role in autism susceptibility. Here, we show that male and female hormones differentially regulate the expression of a novel autism candidate gene, retinoic acid-related orphan receptor-alpha (RORA) in a neuronal cell line, SH-SY5Y. In addition, we demonstrate that RORA transcriptionally regulates aromatase, an enzyme that converts testosterone to estrogen. We further show that aromatase protein is significantly reduced in the frontal cortex of autistic subjects relative to sex- and age-matched controls, and is strongly correlated with RORA protein levels in the brain. These results indicate that RORA has the potential to be under both negative and positive feedback regulation by male and female hormones, respectively, through one of its transcriptional targets, aromatase, and further suggest a mechanism for introducing sex bias in autism.

15. Scheuerle A, Wilson K. {{PARK2 copy number aberrations in two children presenting with autism spectrum disorder: Further support of an association and possible evidence for a new microdeletion/microduplication syndrome}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Feb 25)

Microdeletions of PARK2 have been reported previously in seven patients with autism spectrum disorder. There are no reports of PARK2 microduplications in this population. Presented are two patients, one with deletion and the other with duplication, both with autism spectrum disorder, though their syndromic phenotypes vary. The deletion patient is cognitively normal and ectomorphic: the duplication patient is cognitively impaired, underweight and short. Further, the microduplication patient has demonstrated adverse medication reactions to psychotropic medications active in the dopamine metabolic pathway: cyclopentolate, lisdexamfetamine, methylphenidate. These patients support an association between PARK2 mutations and autism spectrum disorder and suggest that duplications may be equally causative. It is hypothesized that the disparate patient phenotypes may represent a deletion/duplication syndrome and that the adverse medication reactions may be a pharmacogenetic phenomenon. (c) 2011 Wiley-Liss, Inc.

16. Schietecatte I, Roeyers H, Warreyn P. {{Exploring the Nature of Joint Attention Impairments in Young Children with Autism Spectrum Disorder: Associated Social and Cognitive Skills}}. {J Autism Dev Disord};2011 (Mar 1)

It is generally accepted that joint attention skills are impaired in children with autism spectrum disorder (ASD). In this study, social preference, attention disengagement and intention understanding, assumed to be associated with the development of joint attention, are explored in relation to joint attention skills in children with ASD at the age of 36 months. Response to joint attention was related to intention understanding, whereas the number of joint attention initiations was associated with attention disengagement, and somewhat less stronger with social preference. The level on which children initiated joint attention was related to social preference. Possible interpretations of these findings are discussed.

17. Shumway S, Thurm A, Swedo SE, Deprey L, Barnett LA, Amaral DG, Rogers SJ, Ozonoff S. {{Brief Report: Symptom Onset Patterns and Functional Outcomes in Young Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (Mar 1)

This study examined the relationship between onset status and current functioning using a recently proposed onset classification system in 272 young children with autism spectrum disorder (ASD). Participants were classified into one of the following groups, based on parent report using the Autism Diagnostic Interview-Revised: Early Onset (symptoms by 12 months, no loss), Delay + Regression (symptoms by 12 months plus loss), Plateau (no early symptoms or loss), and Regression (no early symptoms, followed by loss). Findings indicate that current functioning does not differ according to onset pattern, calling into question the use of onset categorizations for prognostic purposes in children with ASD.

18. Smith CL, Bolton A, Nguyen G. {{Genomic and epigenomic instability, fragile sites, schizophrenia and autism}}. {Curr Genomics};2010 (Sep);11(6):447-469.

Increasing evidence links genomic and epigenomic instability, including multiple fragile sites regions to neuropsychiatric diseases including schizophrenia and autism. Cancer is the only other disease associated with multiple fragile site regions, and genome and epigenomic instability is a characteristic of cancer. Research on cancer is far more advanced than research on neuropsychiatric disease; hence, insight into neuropsychiatric disease may be derived from cancer research results. Towards this end, this article will review the evidence linking schizophrenia and other neuropsychiatric diseases (especially autism) to genomic and epigenomic instability, and fragile sites. The results of studies on genetic, epigenetic and environmental components of schizophrenia and autism point to the importance of the folate-methionine-transulfuration metabolic hub that is diseases also perturbed in cancer. The idea that the folate-methionine-transulfuration hub is important in neuropsychiatric is exciting because this hub present novel targets for drug development, suggests some drugs used in cancer may be useful in neuropsychiatric disease, and raises the possibility that nutrition interventions may influence the severity, presentation, or dynamics of disease.

19. Tang B, Piazza CC, Dolezal D, Stein MT. {{Severe Feeding Disorder and Malnutrition in 2 Children With Autism}}. {J Dev Behav Pediatr};2011 (Feb 24)

CASE:: Leanna, a 10-year-old girl with autism, was hospitalized for severe malnutrition and 20 pound weight loss secondary to reduced intake over 4 months. Her food choices became increasingly restrictive to the point where she only ate certain types and brands of foods. She gradually stopped drinking and developed severe constipation and encopresis. A new behavior of collecting saliva in her mouth and spitting onto napkins also emerged.Vital signs and electrolytes were normal on admission. A nasogastric tube was placed because she refused to eat. A behavior modification plan was implemented that awarded points for completing specific tasks related to feeding, which could later be redeemed for specific rewards, such as computer time. Although her ideal body weight increased from 68% to 75% (due to continuous nasogastric tube feeds), her refusal to eat persisted.Upon further data gathering, the staff learned that she moved and changed schools 5 months ago. She was cared for by either a family friend or paid caregiver while her mother worked. Although she could conduct basic self-care activities without assistance and write and draw at a third-grade level, she functioned cognitively at a 4-year-old level. The behavior plan was modified, breaking the tasks into shorter components with immediate and tangible rewards. She soon began eating small portions of food and spitting less frequently. Toileting was later incorporated into this plan. She was referred to a behavioral therapist in the community to work with her at home and school. Weekly visits with her pediatrician and appointments with a child psychiatrist and dietician were made.Orlando, a 3-year-old boy with autism, was evaluated in the emergency room for lethargy and generalized edema for 6 weeks. The history revealed a restrictive diet of commercial pureed fruit and coconut juice for 2 years. He only ate a particular brand and with specific containers; the limited food intake occurred only with his favorite blanket. He refused to eat other types of food. Outpatient treatments were unsuccessful.On physical examination, he was irritable with an erythematous, scaly rash throughout his body. His hair was thin, coarse, and blonde. He had nonpitting edema in his arms, legs, and periorbital region. The laboratory evaluation was significant for anemia, hypoalbuminemia, and hypoproteinemia.He was admitted to the pediatric service where nutritional formula feedings were initiated through a nasogastric tube. Weight gain was adequate, and the hemoglobin, serum albumen, and protein became normal. The rash improved with zinc supplementation. He was transferred to an inpatient feeding disorders unit where a team of occupational therapists implemented a behavioral modification program to overcome his severe food aversion.

20. Tasdemiroglu E, Kaya M, Yildirim CH, Firat L. {{Response letter to editor: cerebellar mutism and autistic spectrum disorder}}. {Childs Nerv Syst};2011 (Mar 1)

21. Zayat M, Kalb L, Wodka EL. {{Brief Report: Performance Pattern Differences Between Children with Autism Spectrum Disorders and Attention Deficit-Hyperactivity Disorder on Measures of Verbal Intelligence}}. {J Autism Dev Disord};2011 (Mar 1)

Performance patterns on verbal subtests from the WISC-IV were compared between a clinically-referred sample of children with either autism spectrum disorders (ASD) or attention deficit/hyperactivity disorder (ADHD). Children with ASD demonstrated a statistically significant stepwise pattern where performance on Similarities was best, followed by Vocabulary, then Comprehension. Although children with ASD and ADHD share multiple behavioral features, this pattern was not observed for those with ADHD. Greater deficits in social reasoning and verbal formulation for children with ASD (compared to ADHD) are hypothesized to account for this observed difference in their performance pattern. Clinical implications, including use of this identified pattern in combination with other symptoms suggestive of ASD in referral decision making are discussed.