1. Allen-Brady K, Robison R, Cannon D, Varvil T, Villalobos M, Pingree C, Leppert MF, Miller J, McMahon WM, Coon H. {{Genome-wide linkage in Utah autism pedigrees}}. {Mol Psychiatry} (Oct);15(10):1006-1015.
Genetic studies of autism over the past decade suggest a complex landscape of multiple genes. In the face of this heterogeneity, studies that include large extended pedigrees may offer valuable insights, as the relatively few susceptibility genes within single large families may be more easily discerned. This genome-wide screen of 70 families includes 20 large extended pedigrees of 6-9 generations, 6 moderate-sized families of 4-5 generations and 44 smaller families of 2-3 generations. The Center for Inherited Disease Research (CIDR) provided genotyping using the Illumina Linkage Panel 12, a 6K single-nucleotide polymorphism (SNP) platform. Results from 192 subjects with an autism spectrum disorder (ASD) and 461 of their relatives revealed genome-wide significance on chromosome 15q, with three possibly distinct peaks: 15q13.1-q14 (heterogeneity LOD (HLOD)=4.09 at 29 459 872 bp); 15q14-q21.1 (HLOD=3.59 at 36 837 208 bp); and 15q21.1-q22.2 (HLOD=5.31 at 55 629 733 bp). Two of these peaks replicate earlier findings. There were additional suggestive results on chromosomes 2p25.3-p24.1 (HLOD=1.87), 7q31.31-q32.3 (HLOD=1.97) and 13q12.11-q12.3 (HLOD=1.93). Affected subjects in families supporting the linkage peaks found in this study did not reveal strong evidence for distinct phenotypic subgroups.
2. Brookman-Frazee LI, Taylor R, Garland AF. {{Characterizing community-based mental health services for children with autism spectrum disorders and disruptive behavior problems}}. {J Autism Dev Disord} (Oct);40(10):1188-1201.
This study describes the characteristics of children with autism spectrum disorders (ASD) with disruptive behavior problems served in community-based mental health clinics, characterizes psychotherapy process and outcome, and examines differences between children with ASD and a non-ASD comparison group. Results indicate that children with ASD served in this setting are high functioning and diagnostically complex. Certain research-based behavioral and cognitive behavioral psychotherapeutic strategies were observed frequently, while parent training strategies and active teaching strategies were observed less frequently. The intensity or thoroughness with which strategies were pursued was relatively low. Outcome analyses indicate improvement in child symptoms and family functioning. Treatment delivery and outcome were similar for children with and without ASD. These findings represent the first detailed observational data characterizing community-based mental health services for children with ASD.
3. Brooks-Kayal A. {{Epilepsy and autism spectrum disorders: are there common developmental mechanisms?}}. {Brain Dev} (Oct);32(9):731-738.
Autistic spectrum disorders (ASD) and epilepsies are heterogeneous disorders that have diverse etiologies and pathophysiologies. The high rate of co-occurrence of these disorders suggest potentially shared underlying mechanisms. A number of well-known genetic disorders share epilepsy and autism as prominent phenotypic features, including tuberous sclerosis, Rett syndrome, and fragile X. In addition, mutations of several genes involved in neurodevelopment, including ARX, DCX, neuroligins and neuropilin2 have been identified in children with epilepsy, ASD or often both. Finally, in animal models, early-life seizures can result in cellular and molecular changes that could contribute to learning and behavioral disabilities as seen in ASD. Increased understanding of the common genetic, molecular and cellular mechanisms of ASD and epilepsy may provide insight into their underlying pathophysiology and elucidate new therapeutic approaches of both conditions.
4. Correia CT, Almeida JP, Santos PE, Sequeira AF, Marques CE, Miguel TS, Abreu RL, Oliveira GG, Vicente AM. {{Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions}}. {Pharmacogenomics J} (Oct);10(5):418-430.
Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.
5. de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C. {{Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives}}. {J Pediatr Gastroenterol Nutr} (Oct);51(4):418-424.
OBJECTIVES: Intestinal permeability (IPT) was investigated in patients with autism as well as in their first-degree relatives to investigate leaky gut hypothesis. Faecal calprotectin (FC) was also measured in patients with autism, either with or without gastrointestinal symptoms, and in their first-degree relatives. PATIENTS AND METHODS: IPT results, assessed by means of the lactulose/mannitol test, were compared with adult and child controls and with FC values. RESULTS: A high percentage of abnormal IPT values were found among patients with autism (36.7%) and their relatives (21.2%) compared with normal subjects (4.8%). Patients with autism on a reported gluten-casein-free diet had significantly lower IPT values compared with those who were on an unrestricted diet and controls. Gastrointestinal symptoms were present in 46.7% of children with autism: constipation (45.5%), diarrhoea (34.1%), and others (alternating diarrhoea/constipation, abdominal pain, etc: 15.9%). FC was elevated in 24.4% of patients with autism and in 11.6% of their relatives; it was not, however, correlated with abnormal IPT values. CONCLUSIONS: The results obtained support the leaky gut hypothesis and indicate that measuring IPT could help to identify a subgroup of patients with autism who could benefit from a gluten-free diet. The IPT alterations found in first-degree relatives suggest the presence of an intestinal (tight-junction linked) hereditary factor in the families of subjects with autism.
6. Deonna T, Roulet-Perez E. {{Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate}}. {Brain Dev} (Oct);32(9):746-752.
Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome) may present as a developmental language disturbance and the affected child may also exhibit autistic features. Landau-Kleffner is now seen as the rare and severe end of a spectrum of cognitive-behavioural symptoms that can be seen in idiopathic (genetic) focal epilepsies of childhood, the benign end being the more frequent typical rolandic epilepsy. Several recent studies show that many children with rolandic epilepsy have minor developmental cognitive and behavioural problems and that some undergo a deterioration (usually temporary) in these domains, the so-called « atypical » forms of the syndrome. The severity and type of deterioration correlate with the site and spread of the epileptic spikes recorded on the electroencephalogram within the perisylvian region, and continuous spike-waves during sleep (CSWS) frequently occur during this period of the epileptic disorder. Some of these children have more severe preexisting communicative and language developmental disorders. If early stagnation or regression occurs in these domains, it presumably reflects epileptic activity in networks outside the perisylvian area, i.e. those involved in social cognition and emotions. Longitudinal studies will be necessary to find out if and how much the bioelectrical abnormalities play a causal role in these subgroup of children with both various degrees of language and autistic regression and features of idiopathic focal epilepsy. One has to remember that it took nearly 40 years to fully acknowledge the epileptic origin of aphasia in Landau-Kleffner syndrome and the milder acquired cognitive problems in rolandic epilepsies.
7. Dereu M, Warreyn P, Raymaekers R, Meirsschaut M, Pattyn G, Schietecatte I, Roeyers H. {{Screening for autism spectrum disorders in flemish day-care centres with the checklist for early signs of developmental disorders}}. {J Autism Dev Disord} (Oct);40(10):1247-1258.
A new screening instrument for ASD was developed that can be filled out by child care workers: the Checklist for Early Signs of Developmental Disorders (CESDD). The predictive validity of the CESDD was evaluated in a population of 6,808 children between 3 and 39 months attending day-care centres in Flanders. The CESDD had a sensitivity of .80 and a specificity of .94. Based on the screening procedure used in this study, 41 children were diagnosed with ASD or got a working diagnosis of ASD. Thus, including child care workers’ report on signs of ASD in screening procedures can help to identify cases of ASD at a young age.
8. Ekas NV, Lickenbrock DM, Whitman TL. {{Optimism, social support, and well-being in mothers of children with autism spectrum disorder}}. {J Autism Dev Disord} (Oct);40(10):1274-1284.
This study used structural equation modeling to examine the relationship between multiple sources of social support (e.g., partner, family, and friends), optimism, and well-being among mothers of children with ASD. Social support was examined as a mediator and moderator of the optimism-maternal well-being relationship. Moreover, the role of optimism as a mediator of the social support-maternal well-being relationship was also evaluated. Results revealed that family support was associated with increased optimism that, in turn, predicted higher levels of positive maternal outcomes and lower levels of negative maternal outcomes. In addition, partner and friend support were directly associated with maternal outcomes. Implications for the development of interventions directed at increasing the quality of social support networks are discussed.
9. Ellis Weismer S, Lord C, Esler A. {{Early language patterns of toddlers on the autism spectrum compared to toddlers with developmental delay}}. {J Autism Dev Disord} (Oct);40(10):1259-1273.
This study characterized early language abilities in toddlers with autism spectrum disorders (n = 257) using multiple measures of language development, compared to toddlers with non-spectrum developmental delay (DD, n = 69). Findings indicated moderate to high degrees of agreement among three assessment measures (one parent report and two direct assessment measures). Performance on two of the three measures revealed a significant difference in the profile of receptive-expressive language abilities for toddlers with autism compared to the DD group, such that toddlers with autism had relatively more severe receptive than expressive language delays. Regression analyses examining concurrent predictors of language abilities revealed both similarities in significant predictors (nonverbal cognition) and differences (frequency of vocalization, imitation) across the diagnostic groups.
10. Fehr S, Downs J, Bebbington A, Leonard H. {{Atypical presentations and specific genotypes are associated with a delay in diagnosis in females with Rett syndrome}}. {Am J Med Genet A} (Oct);152A(10):2535-2542.
There is often delay between onset of Rett syndrome symptoms and its diagnosis, possibly related to symptom presentation or socio-demographic factors. We hypothesized that girls with an atypical presentation or whose family had a lower socio-economic status would receive a later diagnosis. Female subjects with a confirmed diagnosis of Rett syndrome were sourced from the Australian Rett Syndrome and InterRett Databases. Variables analyzed included timing and development of symptoms; MECP2 mutation type; parental occupation and education; maternal age and birth order. Residential location and socio-economic status were also analyzed for the Australian cases. Linear regression was used to determine relationships between these factors and age at diagnosis. A total of 909 cases were included. An older age of diagnosis was associated with later loss of hand function and speech, later onset of hand stereotypies and the presence of the p.R133C or p.R294X MECP2 mutation. Socio-economic factors did not predict age of diagnosis for Australian families. For families participating in the InterRett database, a younger age of diagnosis was associated with higher levels of parental education or occupation. A clinical picture consistent with the classic presentation of Rett syndrome is associated with an earlier diagnosis. Clinicians need to be alerted to the variable presentation of Rett syndrome including the milder phenotypes of cases with the p.R133C or p.R294X mutation. Educational resources to assist this understanding including guidance on when to request genetic testing could be useful to streamline the process of diagnosis in Rett syndrome.
11. Fournier KA, Hass CJ, Naik SK, Lodha N, Cauraugh JH. {{Motor coordination in autism spectrum disorders: a synthesis and meta-analysis}}. {J Autism Dev Disord} (Oct);40(10):1227-1240.
Are motor coordination deficits an underlying cardinal feature of Autism Spectrum Disorders (ASD)? Database searches identified 83 ASD studies focused on motor coordination, arm movements, gait, or postural stability deficits. Data extraction involved between-group comparisons for ASD and typically developing controls (N = 51). Rigorous meta-analysis techniques including random effects models, forest and funnel plots, I (2), publication bias, fail-safe analysis, and moderator variable analyses determined a significant standardized mean difference effect equal to 1.20 (SE = 0.144; p <0.0001; Z = 10.49). This large effect indicated substantial motor coordination deficits in the ASD groups across a wide range of behaviors. The current overall findings portray motor coordination deficits as pervasive across diagnoses, thus, a cardinal feature of ASD.
12. Fox NS, Roman AS. {{Beta 2 adrenergic agents and autism}}. {Am J Obstet Gynecol} (Oct);203(4):e15; author reply e15-16.
13. Gabis L, Raz R, Kesner-Baruch Y. {{Paternal age in autism spectrum disorders and ADHD}}. {Pediatr Neurol} (Oct);43(4):300-302.
Increased paternal age has been associated with an increased risk for autism spectrum disorders. The present study compared the paternal age distribution in autism spectrum disorders children with that of the general population and among children with attention deficit hyperactivity disorder. Study participants were drawn from the records of children diagnosed with one of these conditions in the years 1998-2006 at the Weinberg Child Development Center, Israel. Data regarding paternal age distribution in the general Israeli population were drawn from the yearly official publications of the Central Bureau of Statistics, Israel. Paternal age at the child’s birth was found for autism spectrum disorders children (n = 268) and attention deficit hyperactivity disorders children (n = 320). Paternal age distribution of the attention deficit hyperactivity disorder children was similar to that of the general population in Israel, whereas autism spectrum disorders children were born to older fathers, compared with either the general population (P < 0.001) or children with attention deficit hyperactivity disorder (P = 0.04). These results support the claim that increased paternal age is associated with a birth of a child with autism spectrum disorders, but indicate that this finding cannot be generalized to attention deficit hyperactivity disorder.
14. Gadow KD, DeVincent CJ, Pisarevskaya V, Olvet DM, Xu W, Mendell NR, Finch SJ, Hatchwell E. {{Parent-child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder}}. {Prog Neuropsychopharmacol Biol Psychiatry} (Oct 1);34(7):1208-1214.
The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent-child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother-child (MC) and father-child (FC) dyads. Mothers completed a validated DSM-IV-referenced rating scale. Partial eta-squared (etap(2)) was used to determine the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate, and >0.14=large. Analyses indicated that children in MC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe mother-rated oppositional-defiant (etap(2)=0.11) and separation anxiety (etap(2)=0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe obsessive-compulsive behaviors (etap(2)=0.19) and tics (etap(2)=0.18). Youths whose parents were both noncarriers had less severe tics than peers with at least one parental carrier, and the effect size was large (etap(2)=0.16). There was little evidence that noncarrier children were rated more severely by mothers who were carriers versus noncarriers. Transmission Disequilibrium Test analyses provided preliminary evidence for undertransmission of the 2-repeat allele in youths with more severe tics (p=0.02). Parent genotype may be helpful in constructing prognostic biomarkers for behavioral disturbances in ASD; however, findings are tentative pending replication with larger, independent samples.
15. Ghanizadeh A. {{Factor analysis on ADHD and autism spectrum disorder DSM-IV-derived items shows lack of overlap}}. {Eur Child Adolesc Psychiatry} (Oct);19(10):797-798.
16. Greenaway R, Howlin P. {{Dysfunctional attitudes and perfectionism and their relationship to anxious and depressive symptoms in boys with autism spectrum disorders}}. {J Autism Dev Disord} (Oct);40(10):1179-1187.
In spite of increasing interest in cognitive behaviour therapy for emotional disorders in children with autism spectrum disorders (ASD), little research has explored the relevance of the cognitive model in this population. This study explores dysfunctional attitudes and perfectionism in boys with ASD and the relationship with anxious and depressive symptoms. Compared to a typically developing group (n = 42), boys with ASD (n = 41) endorsed more dysfunctional attitudes and reported higher emotional symptoms. The relationship between emotional and cognitive variables was weak in both groups, although in the ASD group dysfunctional attitudes were significantly associated with reported obsessive-compulsive symptoms. Reasons for elevated dysfunctional attitudes in the ASD group are discussed and the roles of cognitive inflexibility and social impairments are explored.
17. Kalyva E. {{Multirater congruence on the social skills assessment of children with asperger syndrome: self, mother, father, and teacher ratings}}. {J Autism Dev Disord} (Oct);40(10):1202-1208.
Children with Asperger Syndrome (AS) who attend mainstream settings face social skills deficits that have not been adequately explored. This study aims to examine social skills through self-reports of children with AS (N = 21) and a matched group of typically developing peers, as well as reports from their mothers, fathers, and teachers. Results showed that children with AS had more social skills deficits according to all raters and that they reported more aggressiveness/antisocial behavior, more conceit/haughtiness, more loneliness/social anxiety, and less assertiveness than controls. The level of agreement between raters varied significantly, suggesting that social skills are best studied with multiple informants.
18. Kawasaki Y, Shinomiya M, Takayanagi M, Niwa S. {{Paroxysmal EEG abnormalities and epilepsy in pervasive developmental disorders: follow-up study until adolescence and beyond}}. {Brain Dev} (Oct);32(9):769-775.
This study examined paroxysmal abnormalities and epilepsy in EEG for individuals with pervasive developmental disorders (PDD) in two parts: first with a large number of subjects (n=1624); and second with extracted subjects followed from 5 years into adolescence and beyond (n=92). Many paroxysms in PDD patients in their childhood tended to appear at various sites and the same held for paroxysms at the time of epilepsy onset. However, in adolescence and beyond, paroxysms in the frontal region prevailed as those appearing at sites other than the frontal region tended to disappear. The same held for paroxysms at the time of epilepsy onset. These paroxysms in the frontal area characteristic of PDD were named « Paroxysms at F. » It was suggested that functional abnormality in the frontal region exists in PDD through paroxysmal EEG abnormalities and epilepsy.
19. Koenig K, White SW, Pachler M, Lau M, Lewis M, Klin A, Scahill L. {{Promoting social skill development in children with pervasive developmental disorders: a feasibility and efficacy study}}. {J Autism Dev Disord} (Oct);40(10):1209-1218.
A randomized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders. Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy. Forty-four children, ages 8-11 years, were randomly assigned to treatment or wait list. Treatment consisted of a 16-week group intervention designed to teach appropriate social behavior. Between group comparisons showed that children in treatment were rated as improved on the primary outcome measure, (unblinded parent report), but not on the secondary outcome measure, a parent questionnaire. Parents reported a high level of satisfaction with the intervention. The study supports the feasibility of this intervention to families and highlights challenges for future research in social skills intervention.
20. Kumar R. {{SHANK2 redemption: another synaptic protein for mental retardation and autism}}. {Clin Genet} (Aug 30)
Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation Berkel et al. (2010) Nature Genetics 42(6):489-491.
21. Loirat C, Bellanne-Chantelot C, Husson I, Deschenes G, Guigonis V, Chabane N. {{Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion}}. {Nephrol Dial Transplant} (Oct);25(10):3430-3433.
BACKGROUND: We report autism in 3 out of 53 children with cystic or hyperechogenic kidneys and heterozygous 17q12 region deletion encompassing hepatocyte nuclear factor-1beta (HNF1B). RESULTS: They presented mental retardation, social interaction impairments, verbal and non-verbal communication deficits and stereotyped behaviours. Deletion size and location of breakpoints were similar to those reported in patients with renal disease/diabetes only. CONCLUSION: Reciprocal genomic rearrangements of the 17q12 region, reported in patients with mental retardation and epilepsy, could also be involved in autism. Nephrologists should be aware of the possibility of autism in patients with 17q12 deletion including HNF1B locus.
22. Luppanapornlarp S, Leelataweewud P, Putongkam P, Ketanont S. {{Periodontal status and orthodontic treatment need of autistic children}}. {World J Orthod} (Fall);11(3):256-261.
23. Mandell DS, Morales KH, Xie M, Polsky D, Stahmer A, Marcus SC. {{County-level variation in the prevalence of medicaid-enrolled children with autism spectrum disorders}}. {J Autism Dev Disord} (Oct);40(10):1241-1246.
This study examined how county-level resources are associated with the identification of children with autism spectrum disorders (ASD) in Medicaid. Medicaid claims from 2004 were combined with county-level data. There were 61,891 children diagnosed with ASD in the Medicaid system in 2004. Counties with lower per-student education expenditures, more students, a greater proportion of students in special education, higher per capita number of pediatricians and pediatric specialists, and a greater proportion of Medicaid enrollees and white residents had higher Medicaid prevalence. Within states, counties differ in how they implement Medicaid policies. The results suggest the substitution of education and Medicaid-reimbursed services. Our findings highlight the need for geographically targeted outreach to minority groups and clinicians to improve recognition of ASD.
24. Matsuo M, Maeda T, Sasaki K, Ishii K, Hamasaki Y. {{Frequent association of autism spectrum disorder in patients with childhood onset epilepsy}}. {Brain Dev} (Oct);32(9):759-763.
Autism spectrum disorder (ASD) has a close relationship with epilepsy. This study retrospectively examined patients with epilepsy associated with ASD. Among the 519 patients with epilepsy, 79 patients (15.2%) had ASD. Sixty-two patients had idiopathic ASD and 17 had secondary ASD. The epilepsy patients with idiopathic ASD were retrospectively analyzed. There were 47 males and 15 females, ranging from 2 to 43 years of age (median 11 years). The most frequent age at the onset of seizures was 4 years, and 85% occurred before 10. ASD was detected after the onset of epilepsy in 29 cases (46.8%), and eight of them had been overlooked for more than five years. Most of these were high-functioning ASD cases. The most frequent type of seizure was a complex partial seizure (CPS; 68%). Paroxysmal activities on EEG were localized in the frontal area in about half of the cases. Multiple anti-epileptic drugs were used in 33.8% cases (two in 17.7%, three in 16.1%), and 67.3% of the patients were seizure-free for more than two years. An amelioration of the autistic symptoms occurred after epilepsy treatment in five cases (8%). CPS with frontal paroxysms occurring from one to nine years of age seems to be characteristic of epilepsy associated with ASD.
25. Murray MJ. {{Attention-deficit/Hyperactivity Disorder in the context of Autism spectrum disorders}}. {Curr Psychiatry Rep} (Oct);12(5):382-388.
Autism spectrum disorders (ASD) are frequently marked by symptoms consistent with attention-deficit/hyperactivity disorder (ADHD), namely inattention, hyperactivity, and impulsivity. Recent work has established that about half of the ASD population also meets diagnostic criteria for ADHD, although the comorbid diagnoses are precluded by the DSM-IV-TR. Individuals with co-occurring ASD and ADHD symptoms are more severely impaired, with significant deficits seen in social processing, adaptive functioning, and executive control. Children with ASD and ADHD symptoms are also prone to motor problems, which lead to especially poor outcomes. Recent work has also demonstrated high rates of ASD symptoms in a subset of children with ADHD. Medication studies have demonstrated the efficacy of methylphenidate, atomoxetine, and guanfacine, among others, in treating ADHD symptoms co-occurring with ASD. However, these effects were not as great as those seen when treating primary ADHD, and they are less well-tolerated in the ASD population.
26. Parmeggiani A, Barcia G, Posar A, Raimondi E, Santucci M, Scaduto MC. {{Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders}}. {Brain Dev} (Oct);32(9):783-789.
The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal abnormalities (PA) are frequently recorded in patients with autism, although the influence of epilepsy and/or EEG PA on the autistic regression has not been clarified yet. We examine a large sample of 345 inpatients with autism, divided into three groups: (1) patients without epilepsy and EEG PA; (2) patients with EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions. The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that reported in the general population. The significant differences among the three groups concerned autistic regression (comparison between groups 1 and 2, p<0.05; comparison between groups 1 and 3, p<0.01), cerebral lesions (comparison between groups 1 and 2, p<0.05; between groups 1 and 3, p<0.001), and symptomatic autism (comparison between groups 1 and 2 as much as comparison between groups 1 and 3, p<0.001), which were prevalent in groups 2 and 3; while severe/profound mental retardation was more frequent in group 3 compared to group 1 (p<0.01). Focal epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group with epilepsy. EEG PA were mainly localized in temporal and central areas (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep. Seizures and EEG PA were not related to autistic regression. EEG PA occurred mainly in childhood, while epilepsy tended to occur (p<0.001) as age increased. The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15 years with no difference between idiopathic and symptomatic cases. In 58.5% of subjects aged > or = 20 years, epilepsy including febrile seizures occurred at some point of their lives, while cases with only EEG PA were less frequent (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified and investigated. In autism, seizures and EEG PA could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions.
27. Perkins T, Stokes M, McGillivray J, Bittar R. {{Mirror neuron dysfunction in autism spectrum disorders}}. {J Clin Neurosci} (Oct);17(10):1239-1243.
Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity.
28. Quintero-Rivera F, Sharifi-Hannauer P, Martinez-Agosto JA. {{Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review}}. {Am J Med Genet A} (Oct);152A(10):2459-2467.
The screening of individuals with mild dysmorphic features and mental retardation using whole genome scanning technologies has resulted in the delineation of several previously unrecognized microdeletion syndromes. Microdeletion of 3q29 has been recently described as one such new syndrome. The clinical phenotype is variable despite an almost identical submicroscopic deletion size in most cases. We report on two individuals that further expand the clinical presentation of this rare disorder and compare the findings with earlier reports to refine the 3q29 microdeletion syndrome phenotype. The propositi are a 10-year-old female and a 15-year-old male, who have in common intellectual disabilities, a history of autism and psychiatric symptoms ranging from bipolar disorder presenting with increasing suicidal ideation to aggressive behavior and general anxiety. Other shared physical findings include asymmetric face, high-nasal bridge, crowded/dysplastic teeth, and tapered fingers. Oligonucleotide array-based chromosomal microarray analysis (CMA) using a genome-wide SNP array identified a de novo subtelomeric microdeletion of chromosome region 3q29 ranging from 1.6 to 2.1 Mb. The region of overlap encompasses 20 RefSeq genes, including FBX045, DLG1, and PAK2. These genes are related to neuronal postsynaptic membrane function and PTEN signaling, suggesting a role for synaptic connectivity dysfunction in the etiology of autism in these children. The novel clinical presentation of our patients expands the clinical spectrum of the 3q29 microdeletion syndrome and provides additional insights into the pathophysiology of autism and psychiatric disorders.
29. Redfern RE, Daou MC, Li L, Munson M, Gericke A, Ross AH. {{A mutant form of PTEN linked to autism}}. {Protein Sci} (Oct);19(10):1948-1956.
The tumor suppressor, phosphatase, and tensin homologue deleted on chromosome 10 (PTEN), is a phosphoinositide (PI) phosphatase specific for the 3-position of the inositol ring. PTEN has been implicated in autism for a subset of patients with macrocephaly. Various studies identified patients in this subclass with one normal and one mutated PTEN gene. We characterize the binding, structural properties, activity, and subcellular localization of one of these autism-related mutants, H93R PTEN. Even though this mutation is located at the phosphatase active site, we find that it affects the functions of neighboring domains. H93R PTEN binding to phosphatidylserine-bearing model membranes is 5.6-fold enhanced in comparison to wild-type PTEN. In contrast, we find that binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) model membranes is 2.5-fold decreased for the mutant PTEN in comparison to wild-type PTEN. The structural change previously found for wild-type PTEN upon interaction with PI(4,5)P(2), is absent for H93R PTEN. Consistent with the increased binding to phosphatidylserine, we find enhanced plasma membrane association of PTEN-GFP in U87MG cells. However, this enhanced plasma membrane association does not translate into increased PI(3,4,5)P(3) turnover, since in vivo studies show a reduced activity of the H93R PTEN-GFP mutant. Because the interaction of PI(4,5)P(2) with PTEN’s N-terminal domain is diminished by this mutation, we hypothesize that the interaction of PTEN’s N-terminal domain with the phosphatase domain is impacted by the H93R mutation, preventing PI(4,5)P(2) from inducing the conformational change that activates phosphatase activity.
30. Rezaei V, Mohammadi MR, Ghanizadeh A, Sahraian A, Tabrizi M, Rezazadeh SA, Akhondzadeh S. {{Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder}}. {Prog Neuropsychopharmacol Biol Psychiatry} (Oct 1);34(7):1269-1272.
BACKGROUND: Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. METHOD: Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate+risperidone (Group A) or placebo+risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for <30 kg and 200 mg/day for >30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. RESULTS: Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. CONCLUSION: The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial.
31. Sasaki M, Nakagawa E, Sugai K, Shimizu Y, Hattori A, Nonoda Y, Sato N. {{Brain perfusion SPECT and EEG findings in children with autism spectrum disorders and medically intractable epilepsy}}. {Brain Dev} (Oct);32(9):776-782.
OBJECTIVE: We performed brain perfusion single-photon emission computed tomography (SPECT) to detect the abnormal brain region in children with both autism spectrum disorders (ASD) and medically intractable epilepsy. METHODS: Fifteen children aged 4-16 years underwent multimodal examinations (MRI, interictal and/or ictal ECD-SPECT, EEG and MEG) to investigate their indications for surgical treatment. All children were diagnosed with ASD according to DSM-IV criteria and intractable epilepsy. Despite medical treatment for more than a year, all experienced at least one seizure per month. All had no underlying basic disorders. Each SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). The relationship between the eZIS pattern and EEG abnormalities or clinical symptoms was investigated. RESULTS: All children showed focal abnormal patterns on eZIS and focal spikes on EEG. In all children, eZIS revealed a mixed hypoperfusion pattern, especially in the prefrontal cortex, medial frontal cortex, anterior cingulate cortex, medial parietal cortex, and/or anterior temporal cortex. In seven of 12 children who underwent interictal SPECT studies, areas of hypoperfusion were related to the focus observed on EEG; in six children, the focal EEG spikes represented areas of hyperperfusion. The children were divided into two groups according to the main type of hypoperfusion patterns seen on eZIS; medial-cingulate type and temporal type. No significant relationship was observed between the areas of hypoperfusion and clinical symptoms. eZIS showed the epileptic focus clearly on ictal SPECT. CONCLUSIONS: SPECT was useful to detect the abnormal brain region not only in searching for the epileptic focus but also in assessing the low or high functioning region of the brain.
32. Seskin L, Feliciano E, Tippy G, Yedloutschnig R, Sossin KM, Yasik A. {{Attachment and autism: parental attachment representations and relational behaviors in the parent-child dyad}}. {J Abnorm Child Psychol} (Oct);38(7):949-960.
While attachment research has demonstrated that parents’ internal working models of attachment relationships tend to be transmitted to their children, affecting children’s developmental trajectories, this study specifically examines associations between adult attachment status and observable parent, child, and dyadic behaviors among children with autism and associated neurodevelopmental disorders of relating and communicating. The Adult Attachment Interview (AAI) was employed to derive parental working models of attachment relationships. The Functional Emotional Assessment Scale (FEAS) was used to determine the quality of relational and functional behaviors in parents and their children. The sample included parents and their 4- to 16-year-old children with autism and associated neurodevelopmental disorders. Hypothesized relationships between AAI classifications and FEAS scores were supported. Significant correlations were found between AAI classification and FEAS scores, indicating that children with autism spectrum disorders whose parents demonstrated secure attachment representations were better able to initiate and respond in two-way pre-symbolic gestural communication; organize two-way social problem-solving communication; and engage in imaginative thinking, symbolic play, and verbal communication. These findings lend support to the relevance of the parent’s state of mind pertaining to attachment status to child and parent relational behavior in cases wherein the child has been diagnosed with autism or an associated neurodevelopmental disorder of relating and communicating. A model emerges from these findings of conceptualizing relationships between parental internal models of attachment relationships and parent-child relational and functional levels that may aid in differentiating interventions.
33. Sevik AE, Cengel Kultur E, Demirel H, Karli Oguz K, Akca O, Lay Ergun E, Demir B. {{[Asperger syndrome with highly exceptional calendar memory: a case report.]}}. {Turk Psikiyatri Derg} (Fall);21(3):249-256.
Some patients with pervasive developmental disorders develop unusual talents, which are characterized as savant syndrome. Herein we present neuropsychological examination and brain imaging (fMRI and brain SPECT) findings of an 18-year-old male with Asperger syndrome and highly unusual calendar memory. Neuropsychological evaluation of the case indicated mild attention, memory, and problem solving deficits, and severe executive function deficits that included conceptualization, category formation, and abstraction. Functional MRI findings showed activation above the baseline level (P < 0.05) in the bilateral inferior parietal lobule, precuneus, superior and middle frontal gyri, and medial frontal cortex. Brain SPECT findings, in comparison to rest-SPECT findings, showed that there was hypoperfusion in some brain regions, including the right frontal cortex and right parietal cortex. Baseline blood perfusion in the left frontal cortex was also observed, as well as hypoperfusion in the right parietal-occipital cortex and in the right basal ganglion (compared to the left side). The results of the present study and further research will contribute to our understanding of calendar memory and savant syndrome.
34. South M, Larson MJ, Krauskopf E, Clawson A. {{Error processing in high-functioning Autism Spectrum Disorders}}. {Biol Psychol} (Oct);85(2):242-251.
Studies report error-processing abnormalities in high-functioning individuals with Autism Spectrum Disorders (ASD) that may be influenced by intelligence and autism severity. Error processing can be measured using the error-related negativity (ERN) and post-error positivity (Pe) components of the event-related potential (ERP), along with behavioral indices such as post-error reaction time (RT) slowing. We used a modified Flanker task to test the hypothesis that high-functioning individuals with ASD would show decreased amplitude ERN in 24 individuals with ASD and 21 age- and IQ-matched typically-developing control participants. Behaviorally, individuals with ASD committed more errors than controls, but groups did not significantly differ on RTs, although there was a trend-level difference in post-error slowing. For ERPs, ERN amplitude was significantly attenuated in individuals with ASD relative to controls; groups did not differ in Pe amplitude. Amplitude of the ERN was not significantly correlated with measures of intelligence, anxiety, behavioral inhibition, or general autism severity.
35. Strom SP, Stone JL, Ten Bosch JR, Merriman B, Cantor RM, Geschwind DH, Nelson SF. {{High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene}}. {Mol Psychiatry} (Oct);15(10):996-1005.
Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 x 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect.
36. Takumi T. {{A humanoid mouse model of autism}}. {Brain Dev} (Oct);32(9):753-758.
Even now fruit of the human genome project is available, we have difficulties to approach neuropsychiatric disorders at the molecular level. Autism is a complex psychiatric illness but has received considerable attention as a developmental brain disorder not only from basic researchers but also from society. Substantial evidence suggests that chromosomal abnormalities contribute to autism risk. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We succeeded to generate mice with a 6.3-Mb-wide interstitial duplication in mouse chromosome 7c that is highly syntenic to human 15q11-13 by using a Cre-loxP-based chromosome-engineering technique. The only paternally duplicated mice display autistic behavioral features such as poor social interaction and stereotypical behavior, and exhibit a developmental abnormality in ultrasonic vocalizations as well as anxiety. The detailed analysis focusing on a non-coding small nucleolar RNA, MBII52, within the duplicated region, revealed that the paternally duplicated mice alter the editing ratio of serotonin (5-HT) 2c receptor pre-mRNA and intracellular calcium responses by a 5-HT2c receptor specific agonist are changed in neurons. This result may explain one of molecular mechanisms of abnormal behaviors in the paternal duplicated mice. The first chromosome-engineered mouse model for human chromosome 15q11-13 duplication fulfills not only face validity of human autistic phenotypes but also construct validity based on human chromosome abnormality. This model will be a founder mouse for forward genetics of autistic disease and an invaluable tool for its therapeutic development.
37. Thanseem I, Nakamura K, Miyachi T, Toyota T, Yamada S, Tsujii M, Tsuchiya KJ, Anitha A, Iwayama Y, Yamada K, Hattori E, Matsuzaki H, Matsumoto K, Iwata Y, Suzuki K, Suda S, Kawai M, Sugihara G, Takebayashi K, Takei N, Ichikawa H, Sugiyama T, Yoshikawa T, Mori N. {{Further evidence for the role of MET in autism susceptibility}}. {Neurosci Res} (Oct);68(2):137-141.
MET receptor tyrosine kinase (MET)-mediated signaling has been implicated in multiple aspects of neocortical and cerebellar neuronal growth and maturation. A promoter functional SNP (rs1858830) that disrupts the transcription of MET has been reported to be strongly associated with autism spectrum disorders (ASD) in the Caucasian population. Here, we performed a trio association study of MET with ASD in Japanese subjects (n=126 trios). Based on the HapMap data on the Japanese population, 15 SNPs were chosen for the association study. One SNP located in intron 1, rs38841, showed a nominal association with autism (p=0.044; OR=1.61) when analyzed using the transmission disequilibrium test. To the best of our knowledge, this is the first replication study of the association of MET with autism, in any non-Caucasian population. Association of rs38841 with autism was further confirmed in 252 Caucasian trios from AGRE (p=0.0006). An interesting observation is that all three SNPs of MET (rs1858830, rs38845 and rs38841) shown to be associated with autism in three independent studies including the present one, are located towards the 5’end of the gene at a span of 9.4 kb. Our results provide further evidence for a possible role of MET in the pathogenesis of ASD.
38. Totsika V, Felce D, Kerr M, Hastings RP. {{Behavior problems, psychiatric symptoms, and quality of life for older adults with intellectual disability with and without autism}}. {J Autism Dev Disord} (Oct);40(10):1171-1178.
The evidence base on outcomes associated with autism in older adulthood is limited. The expected increase in the prevalence of older adults with autism highlights the need to describe their profiles and service needs. Adults 50 years or older with an intellectual disability (ID) and the triad of impairments characteristic of autism spectrum disorders (ASD) were compared to peers with ID only, and younger adults with ASD and ID. After accounting for ability differences, older adults with ASD did not differ from those with ID in terms of behavior problems, psychiatric disorder, and quality of life. Any differences in the skills of adults with ASD were associated with decreased adaptive skills, and not the presence of ASD per se.
39. Tuchman R, Alessandri M, Cuccaro M. {{Autism spectrum disorders and epilepsy: moving towards a comprehensive approach to treatment}}. {Brain Dev} (Oct);32(9):719-730.
The biological and phenotypic heterogeneity of children with autism spectrum disorders (ASD) and epilepsy presents a significant challenge to the development of effective treatment protocols. There is no single treatment or treatment protocol for children with ASD or epilepsy. Children with co-occurring ASD and epilepsy should undergo a comprehensive assessment that includes investigation of underlying biological etiologies as well assessment of cognitive, language, affective, social and behavioral function prior to initiating treatment. The comprehensive treatment of children with ASD is based on a combination of therapeutic psychosocial interventions in combination with pharmacological agents. A process-oriented approach to assessment and intervention allows careful analysis of the child’s response to treatment such that treatment protocols may be revised secondary to any changes in developmental trajectory of the child with ASD and epilepsy. The possibility of developing pharmacological interventions that target both ASD and epilepsy awaits definitive evidence. The best hope for good developmental outcomes in children with ASD and epilepsy is early recognition and comprehensive treatment of both the ASD and epilepsy.
40. Tuchman R, Cuccaro M, Alessandri M. {{Autism and epilepsy: historical perspective}}. {Brain Dev} (Oct);32(9):709-718.
Autism spectrum disorders (ASD) and epilepsy co-occur in approximately 30% of individuals with either ASD or epilepsy. While there is no single unifying ASD-epilepsy phenotype, understanding potential commonalities in subgroups of children with an ASD-epilepsy phenotype will help us disentangle the pathophysiology of both ASD and epilepsy. Throughout this brief historical perspective we selectively review critical trends in ASD-epilepsy research and highlight challenges to clinical and research efforts including terminology, heterogeneity of both ASD and epilepsy, and lack of careful characterization of children affected with both ASD and epilepsy. These complex issues continue to burden research on the diagnosis, neurobiology and management of children with ASD and epilepsy. A key concept that has emerged during the past 40 years is the strong association between intellectual disability and a higher prevalence of epilepsy in individuals with ASD. In addition, the two peaks of seizure onset, one in early childhood and one in adolescence and continuing through adulthood may be unique to individuals with ASD. The overlap of language and autistic regression to epilepsy, EEG epileptiform activity, sleep, and to epileptic encephalopathies such as Landau-Kleffner syndrome continue to be controversial areas of research and of clinical interest. An emerging consensus is that shared developmental genetic, molecular and pathophysiological mechanisms exist and account for the common co-occurrence of ASD and epilepsy.
41. Ward-King J, Cohen IL, Penning H, Holden JJ. {{Brief report: telephone administration of the autism diagnostic interview–revised: reliability and suitability for use in research}}. {J Autism Dev Disord} (Oct);40(10):1285-1290.
The Autism Diagnostic Interview–revised is one of the « gold standard » diagnostic tools for autism spectrum disorders. It is traditionally administered face-to-face. Cost and geographical concerns constrain the employment of the ADI-R for large-scale research projects. The telephone interview is a reasonable alternative, but has not yet been examined for reliability with face-to-face administration. In this study, participants were interviewed both face-to-face and on the telephone using the complete ADI-R interview. Results indicate that there was no significant difference between the algorithm scores or the diagnoses arrived at for face-to-face and telephone administrations. Reliability statistics across the two modalities were very good and indicate that telephone interviews using the ADI-R are a viable option for researchers.
42. Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP. {{Urinary Porphyrin Excretion in Neurotypical and Autistic Children}}. {Environ Health Perspect} (Oct);118(10):1450-1457.
Background: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).Objectives: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.Methods: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.Results: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.Conclusions: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent. Editor’s SummaryIncreased urinary concentrations of pentacarboxylporphyrins, precoproporphyrins and coproporphyrins have been associated with prolonged mercury (Hg) exposure in adults. Comparable increases in urinary prophyrins have been attributed to Hg exposure in children with autism. Woods et al. (p. 1450) compared urinary porphyrin concentrations in neurotypical children and autistic children of the same age. They also examined the association between urinary porphyrin levels and past or current Hg exposure in children with autism. Children 2-12 years of age were categorized into one of three groups: autistic, pervasive developmental disorder-not otherwise specified (PDD-NOS), and neurotypical. Elevated urinary concentrations of coproporphyrin, hexacarboxylporphyrin, and pentacarboxylporphyrin were significantly associated with autism but not with PDD-NOS. Hg exposures were comparable between the two diagnostic groups, and a urinary porphyrin pattern did not appear to be consistent with that seen in Hg-exposed adults. The authors conclude that disordered porphyrin metabolism is a characteristic of autism.
43. Xia W, Zhou Y, Sun C, Wang J, Wu L. {{A preliminary study on nutritional status and intake in Chinese children with autism}}. {Eur J Pediatr} (Oct);169(10):1201-1206.
Parents of children with autism often report gastrointestinal problems as well as picky eating and selective eating in their children. The purpose of this study was to evaluate the nutritional status and the nutrient intake in 111 Chinese children with autism, aged between 2 and 9 years. Anthropometric data were expressed as Z scores. A 3-day dietary recall was provided by the parents, and the data were compared with the national Dietary Reference Intakes (DRI) standards for Chinese children. The results showed that only nine of the autistic children (8.1%) were acute or chronically malnourished. From the remaining 102 patients, 67 (60.4%) were eutrophic and 35 (31.5%) had either overweight or obesity. Intakes of both calories and proteins were adequate in the vast majority of these children, but the calories from fat was lower than DRI in the same age group. The average intake of vitamin E and niacin exceeded 100% of DRI, and the intakes of vitamin B1 and B2, magnesium, and iron were between 80% and 90% of DRI range. However, the following nutrients did not meet the DRI requirements at all: vitamins A, B6 and C, folic acid, calcium, and zinc. Although growth was satisfactory in the vast majority of these children with autistic disorder, this study revealed serious deficiencies in the intakes of several vitamins and essential nutrients.
44. Zappella M. {{Autistic regression with and without EEG abnormalities followed by favourable outcome}}. {Brain Dev} (Oct);32(9):739-745.
OBJECTIVES: To explore the relationship between autistic regression (AR) with and without EEG abnormalities and favourable outcome. METHODS: Follow up data on children with favourable outcome in a series of 534 cases aged below 5 years and diagnosed as ASD. RESULTS: Cases with regression were 167 (31.8%), usually with persistent ASD, intellectual disabilities and EEG abnormalities. Thirty nine children (7.3%) went off autism and recovered entirely their intellectual and social abilities. Few of them included examples of pharmacologically treated Landau and Kleffner syndrome and other similar complex cases with abnormal EEG. The majority was represented by 36 (6.7%) children, mostly males, with a dysmaturational syndrome: their development was initially normal up to 18 months when an autistic regression occurred accompanied by the appearance of motor and vocal tics. Relational therapies were followed by rapid improvement. By 6 years all children had lost features of ASD and their I.Q. was in most cases between 90 and 110. Convulsions were absent and EEG was normal in all cases except one. In a few of them recovery was spontaneous. Seventeen children were followed after 5 years 6 months: 12 (70%) had ADHD, 10 (56%) persistent tics. Tics were often present in parents and relatives, ASD absent, suggesting a genetic background different from cases with persistent ASD. With one exception all « off autism » children had a previous autistic regression. CONCLUSIONS: In this series « off autism » children had either early onset epilepsy and/or EEG abnormalities or cases of dysmaturational syndrome. Autistic regression was present in almost all.
