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1.  Parent Report of Community Psychiatric Comorbid Diagnoses in Autism Spectrum Disorders 
Autism Research and Treatment  2011;2011:405849.
We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD). Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder—not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.
doi:10.1155/2011/405849
PMCID: PMC3420588  PMID: 22937248
2.  Association Between Depression and Anxiety in High-Functioning Children with Autism Spectrum Disorders and Maternal Mood Symptoms 
Autism Research  2010;3(3):120-127.
Research suggests that children with autism spectrum disorders (ASDs) and their relatives have high rates of depression and anxiety. However, relatively few studies have looked at both factors concurrently. This study examined the potential relationship between maternal mood symptoms and depression and anxiety in their children with ASD. Participants were 31 10- to 17-year-old children with an ASD diagnosis that was supported by gold-standard measures and their biological mothers. Mothers completed the Autism Comorbidity Interview to determine whether the child with ASD met criteria for any depressive or anxiety diagnoses and a questionnaire of their own current mood symptoms. As expected, many children with ASD met criteria for lifetime diagnoses of depressive (32%) and anxiety disorders (39%). Mothers’ report of their own current mood symptoms revealed averages within the normal range, though there was significant variability. Approximately 75% of children with ASD could be correctly classified as having a depressive or anxiety disorder history or not based on maternal symptoms of interpersonal sensitivity, hostility, phobic anxiety, depression, and anxiety. The results provide preliminary evidence that maternal mood symptoms may be related to depression and anxiety in their children with ASD. Although the design did not allow for testing of heritability per se, the familial transmission patterns were generally consistent with research in typical populations. While larger follow-up studies are needed, this research has implications for prevention and intervention efforts.
doi:10.1002/aur.133
PMCID: PMC3374580  PMID: 20578069
Autism; Asperger’s disorder; psychiatric comorbidity; anxiety; depression; mood disorders; familial aggregation; maternal symptoms
3.  Autism Spectrum Disorder Scale Scores in Pediatric Mood and Anxiety Disorders 
Objective
To compare scores on autism spectrum disorder (ASD) symptom scales in healthy youths and youths with mood or anxiety disorders.
Method
A total of 352 youths were recruited (107 healthy participants, 88 with an anxiety disorder, 32 with major depressive disorder, 62 with bipolar disorder, and 63 with a mood disorder characterized by severe nonepisodic irritability). Participants received structured psychiatric interviews and parent ratings on at least one of three ASD symptom scales: Children’s Communication Checklist, Social Communication Questionnaire, and Social Responsiveness Scale.
Results
Relative to healthy youths, youths with mood or anxiety disorders exhibited higher scores on each ASD symptom scale. ASD symptom scale scores also showed an association with impairment severity and attention-deficit/hyperactivity disorder. Among patients with mood disorders but not those with anxiety disorders, consistent, statistically significant associations between diagnosis and ASD symptom scale scores remained even after controlling for potential confounders.
Conclusions
Patients with mood disorders exhibit higher scores on ASD symptom scales than healthy youths or youths with anxiety disorders. These data should alert clinicians to the importance of assessing ASD symptoms to identify social reciprocity and communication deficits as possible treatment targets in pediatric mood and anxiety disorders.
doi:10.1097/CHI.0b013e31816bffa5
PMCID: PMC2735817  PMID: 18434923
mood disorder; anxiety disorder; autism spectrum; impairment
4.  Broader Autism Phenotype in Iranian Parents of Children with Autism Spectrum Disorders vs. Normal Children 
Iranian Journal of Psychiatry  2012;7(4):157-163.
Objective
The aim of the present study was to compare the broader autism phenotype in Iranian parents of children with autism spectrum disorders and parents of typically developing children.
Method
Parents of children with ASD and parents of typically developing children were asked to complete the Persian version of the Autism Spectrum Quotient (AQ). In the ASD group, families included 204 parents (96 fathers and 108 mothers) of children diagnosed as having autism (Autistic Disorder, or AD) (n=124), Asperger Syndrome (AS) or High Functioning Autism (HFA) (n=48) and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) (n=32) by psychiatrists based on the Diagnostic and Statistical Manual of Mental Disorders-4thedition (DSM-IV-TR) criteria. In the control group, 210 (108 fathers and 102 mothers) parents of typically developing children. Parents of typically developing children were selected from four primary schools. Based on family reports, their children did not have any psychiatric problems. Total AQ score and each of the 5 subscales were analyzed using two-way ANOVAs with sex and group as factors.
Results
The mean age of ASD fathers was 40.6 years (SD=5.96; range 31-54), and of ASD mothers was 34.7 years (SD=4.55; range 28-45). The mean age of control fathers was 37 years (SD=4.6; range 29-45) and of control mothers was 34.11 years (SD=4.86; range 28-45). Group differences were found in age (p ‹ 0/001). On total AQ, a main effect for group and sex was found. ASD parents scored higher than controls (F(1,410)=77.876, P ‹ 0/001) and males scored higher than females (F(1,410)=23.324, P ‹ 0/001). Also, Group by Sex interaction was significant (F(1,410)=4.986, P ‹ 0/05). Results of MANOVA analysis displayed significant differences between ASD's subgroups on total AQ and subscales scores (F (15, 1121)=13.924, p < 0.0005; Wilk's Lambda= 0.624, partial =0.145). Pairwise comparisons between ASD's subgroups and Normal group showed that mean scores for the Asperger group are significantly more than other groups in total AQ, attention switching and communication subscales (p < 0.05). The frequencies of BAP (X^2=52.721 (DF=1), P ‹ 0/001), MAP (X^2=17.133 (DF=1), P ‹ 0/001) and NAP (X^2=12.722 (DF=1), P ‹ 0/001) in ASD parents were significantly more than control parents. The frequencies of Broader Autism Phenotype (BAP) (X^2=3.842 (DF=1), P›0/05) and Medium Autism phenotype (MAP) (X^2=0.060 (DF=1), P›0/05) did not significantly differ in ASD fathers and mothers, but the proportion of fathers in Narrow Autism Phenotype(NAP) range was more than mothers (X2=14.344, P ‹ 0/001).
Conclusion
Results of the present study revealed that parents of children with ASD scored significantly higher than control parents on total AQ and its subscales and the rates of BAP, MAP and NAP were higher in ASD parents than in controls. In addition, in ASD's subgroups, the parents of Asperger children scored significantly more than other subgroups (Autism and PDD-nos) and the normal group on total AQ and some subscales.
PMCID: PMC3570573  PMID: 23408558
Autistic disorder; Child; Iran; Parents
5.  Adolescents and Adults with Autism with and without Co-morbid Psychiatric Disorders: Differences in Maternal Well-Being 
This study investigated the associations between the characteristics of adolescents and adults with autism spectrum disorders (ASD) and maternal well-being. Two groups were compared: mothers of adolescents and adults with ASD and co-morbid psychiatric disorders (n = 142) and mothers whose sons or daughters had a single diagnosis of ASD (n = 130). Individuals with co-morbid psychiatric disorders had higher levels of repetitive behaviors, asocial behavior, and unpredictability of behavior than their counterparts with ASD only. They also had poorer rated health as well as more frequent gastrointestinal problems and sleep problems. Mothers of sons and daughters with ASD and co-morbid psychiatric disorders reported higher levels of burden and a poorer quality parent-child relationship than mothers of sons and daughters with ASD only. Higher levels of asocial behavior, unpredictability of behavior, and poorer health in sons and daughters with ASD were predictive of greater burden in mothers and a poorer quality parent-child relationship.
doi:10.1080/19315860801988228
PMCID: PMC2885815  PMID: 20556237
autism; co-morbidity; psychiatric disorders; adolescents and adults; burden
6.  Communication, Interventions, and Scientific Advances in Autism: A Commentary 
Physiology & behavior  2010;100(3):268-276.
Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its co-morbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research.
doi:10.1016/j.physbeh.2010.01.003
PMCID: PMC2860058  PMID: 20093134
autism spectrum disorders; social; communication; language; gender differences; behavior modeling; Picture Exchange Communication System; mice; genetics; BTBR; Center for Autism and Related Disabilities; education programs; translational research
7.  A Pilot Study of Maternal Sensitivity in the Context of Emergent Autism 
Unstructured mother-toddler interactions were examined in 18-month-old high- and low-risk children subsequently diagnosed (n=12) or not diagnosed (n=21) with autism spectrum disorders (ASD) at 36 months. Differences in maternal sensitivity were not found as a function of emergent ASD status. A differential-susceptibility moderation model of child risk guided investigations linking maternal sensitivity to child behavior and language growth. Group status moderated the relation between sensitivity and concurrent child behavior problems, with a positive association present for children with emergent ASD. Maternal sensitivity at 18 months predicted expressive language growth from age two to three years among children with emergent ASD only. Findings underscore the importance of understanding parent-child interaction during this key period in the development of autism symptomatology.
doi:10.1007/s10803-010-0948-4
PMCID: PMC2904821  PMID: 20130975
Autism; Risk; Parenting; Parent-Child Interaction; Sensitivity; Language
8.  Sibling Adjustment and Maternal Well-Being: An Examination of Families With and Without a Child With an Autism Spectrum Disorder 
Differences in sibling social, behavioral, and academic adjustment and maternal well-being in families with (n = 20) and without (n = 23) a preschooler with autism spectrum disorder (ASD) were explored. Results are interpreted to suggest that mothers of children with autism report more daily hassles, life stress, and depression than mothers without a child with ASD. There were no significant differences in parent and teacher reports of older siblings’ social, behavioral, and academic adjustment in families with and without a child with ASD. Sibling behavioral adjustment was, however, significantly related to maternal well-being. Because families with children with ASD often experience more parenting stress and depression, siblings may be more vulnerable to the cumulative risks over time.
doi:10.1177/1088357609350367
PMCID: PMC2966315  PMID: 21037802
siblings; autism spectrum disorder; maternal well-being; depression
9.  Aripiprazole Improved Obsessive Compulsive Symptoms in Asperger's Disorder 
There are many comorbid disorders associated with autism spectrum disorders in child and adolescent population. Although obsessive compulsive disorder and autism spectrum disorders (ASD) comorbidity has common in clinical practice, there are few reports about psychopharmacological treatment for obsessive compulsive symptoms in children with ASD in the literacy. We report a successful treatment case with aripiprazole in Asperger's Disorder with obsessive compulsive symptoms. The Yale Brown Obsessive Compulsive Scale was performed to assess symptom variety. This case report supports the effectiveness of aripiprazole in treatment of obsessive compulsive symptoms in Asperger's Disorder or ASDs. Aripiprazole may be beneficial to obsessive compulsive disorder comorbid autism spectrum disorders in child and adolescent age group.
doi:10.9758/cpn.2011.9.3.134
PMCID: PMC3569112  PMID: 23429759
Asperger; Aripiprazole; Obsessive compulsive disorder
10.  Genetic studies in children with intellectual disability and autistic spectrum of disorders 
Indian Journal of Human Genetics  2009;15(3):103-107.
Autism is one of the five disorders that falls under the umbrella of Pervasive Developmental Disorders (PDD) or Autism Spectrum Disorder (ASD), a category of neurological disorders characterized by “severe and pervasive impairment in several areas of development.” ASD is characterized by varying degrees of impairment in communication skills, social interaction and restricted, repetitive stereotyped patterns of behavior. The five disorders under PDD are autistic disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder and PDD-not otherwise specified. ASD can often be reliably detected by the age of 3 years and, in some cases, as early as 18 months. The appearance of any warning signs of ASD is reason to have the child evaluated by a professional specializing in these disorders.
doi:10.4103/0971-6866.60185
PMCID: PMC2922625  PMID: 21088714
Autism; genetics; mental handicap
11.  Sibling recurrence and the genetic epidemiology of autism 
The American journal of psychiatry  2010;167(11):1349-1356.
Objective
Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings.
Method
We report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register who met the criteria of having at least one child clinically-affected by an autism spectrum disorder (ASD) and at least one full biological sibling.
Results
The occurrence of a traditionally-defined ASD in an additional child occurred in 10.9% of the families. An additional 20% of non-ASD-affected siblings had a history of language delay, half of whom had exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale (SRS) supported previously-reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families, and a relative absence of quantitative autistic traits among siblings in single-incidence autism families. Girls whose standardized severity ratings fell above a first percentile severity threshold (relative to the general population distribution) were significantly less likely to have elicited community diagnoses than their male counterparts.
Conclusions
These data suggest that, depending on how it is defined, sibling recurrence in ASD may exceed previously-published estimates, and varies as a function of family type. The results support differences in mechanisms of genetic transmission between simplex and multiplex autism, and advance current understanding of the genetic epidemiology of autism.
doi:10.1176/appi.ajp.2010.09101470
PMCID: PMC2970737  PMID: 20889652
Genetics; Pervasive Developmental Disorder; Language; Broader Autism Phenotype
12.  Autism-Associated Gene Expression in Peripheral Leucocytes Commonly Observed between Subjects with Autism and Healthy Women Having Autistic Children 
PLoS ONE  2011;6(9):e24723.
Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder.
doi:10.1371/journal.pone.0024723
PMCID: PMC3174190  PMID: 21935445
13.  Facial Identity Recognition in the Broader Autism Phenotype 
PLoS ONE  2010;5(9):e12876.
Background
The ‘broader autism phenotype’ (BAP) refers to the mild expression of autistic-like traits in the relatives of individuals with autism spectrum disorder (ASD). Establishing the presence of ASD traits provides insight into which traits are heritable in ASD. Here, the ability to recognise facial identity was tested in 33 parents of ASD children.
Methodology and Results
In experiment 1, parents of ASD children completed the Cambridge Face Memory Test (CFMT), and a questionnaire assessing the presence of autistic personality traits. The parents, particularly the fathers, were impaired on the CFMT, but there were no associations between face recognition ability and autistic personality traits. In experiment 2, parents and probands completed equivalent versions of a simple test of face matching. On this task, the parents were not impaired relative to typically developing controls, however the proband group was impaired. Crucially, the mothers' face matching scores correlated with the probands', even when performance on an equivalent test of matching non-face stimuli was controlled for.
Conclusions and Significance
Components of face recognition ability are impaired in some relatives of ASD individuals. Results suggest that face recognition skills are heritable in ASD, and genetic and environmental factors accounting for the pattern of heritability are discussed. In general, results demonstrate the importance of assessing the skill level in the proband when investigating particular characteristics of the BAP.
doi:10.1371/journal.pone.0012876
PMCID: PMC2943915  PMID: 20877561
14.  Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression 
Translational Psychiatry  2011;1(10):e48-.
The contribution of peripheral immunity to autism spectrum disorders (ASDs) risk is debated and poorly understood. Some mothers of children with ASD have autoantibodies that react to fetal brain proteins, raising the possibility that a subset of ASD cases may be associated with a maternal antibody response during gestation. The mechanism by which the maternal immune system breaks tolerance has not been addressed. We hypothesized that the mechanism may involve decreased expression of the MET receptor tyrosine kinase, an ASD risk gene that also serves as a key negative regulator of immune responsiveness. In a sample of 365 mothers, including 202 mothers of children with ASD, the functional MET promoter variant rs1858830 C allele was strongly associated with the presence of an ASD-specific 37+73-kDa band pattern of maternal autoantibodies to fetal brain proteins (P=0.003). To determine the mechanism of this genetic association, we measured MET protein and cytokine production in freshly prepared peripheral blood mononuclear cells from 76 mothers of ASD and typically developing children. The MET rs1858830 C allele was significantly associated with MET protein expression (P=0.025). Moreover, decreased expression of the regulatory cytokine IL-10 was associated with both the MET gene C allele (P=0.001) and reduced MET protein levels (P=0.002). These results indicate genetic distinction among mothers who produce ASD-associated antibodies to fetal brain proteins, and suggest a potential mechanism for how a genetically determined decrease in MET protein production may lead to a reduction in immune regulation.
doi:10.1038/tp.2011.48
PMCID: PMC3309488  PMID: 22833194
autism; gene; immune; maternal; cytokine
15.  Autism and Intellectual Disability Are Differentially Related to Sociodemographic Background at Birth 
PLoS ONE  2011;6(3):e17875.
Background
Research findings investigating the sociodemographics of autism spectrum disorder (ASD) have been inconsistent and rarely considered the presence of intellectual disability (ID).
Methods
We used population data on Western Australian singletons born from 1984 to 1999 (n = 398,353) to examine the sociodemographic characteristics of children diagnosed with ASD with or without ID, or ID without ASD compared with non-affected children.
Results
The profiles for the four categories examined, mild-moderate ID, severe ID, ASD without ID and ASD with ID varied considerably and we often identified a gradient effect where the risk factors for mild-moderate ID and ASD without ID were at opposite extremes while those for ASD with ID were intermediary. This was demonstrated clearly with increased odds of ASD without ID amongst older mothers aged 35 years and over (odds ratio (OR) = 1.69 [CI: 1.18, 2.43]), first born infants (OR = 2.78; [CI: 1.67, 4.54]), male infants (OR = 6.57 [CI: 4.87, 8.87]) and increasing socioeconomic advantage. In contrast, mild-moderate ID was associated with younger mothers aged less than 20 years (OR = 1.88 [CI: 1.57, 2.25]), paternal age greater than 40 years (OR = 1.59 [CI: 1.36, 1.86]), Australian-born and Aboriginal mothers (OR = 1.60 [CI: 1.41, 1.82]), increasing birth order and increasing social disadvantage (OR = 2.56 [CI: 2.27, 2.97]). Mothers of infants residing in regional or remote areas had consistently lower risk of ASD or ID and may be linked to reduced access to services or under-ascertainment rather than a protective effect of location.
Conclusions
The different risk profiles observed between groups may be related to aetiological differences or ascertainment factors or both. Untangling these pathways is challenging but an urgent public health priority in view of the supposed autism epidemic.
doi:10.1371/journal.pone.0017875
PMCID: PMC3068153  PMID: 21479223
16.  Cognitive profiles and social-communicative functioning in children with autism spectrum disorder 
Background
Whether there is an unusual degree of unevenness in the cognitive abilities of children with autism spectrum disorder (ASD) and whether different cognitive profiles among children with ASD might index etiologically significant subgroups are questions of continued debate in autism research.
Method
The Differential Ability Scales (DAS) and the Autism Diagnostic Observation Schedule (ADOS) were used to examine profiles of verbal and nonverbal abilities and their relationship to autistic symptomatology in 120 relatively high-functioning children with ADI-confirmed diagnoses of autism.
Results
Discrepancies between verbal and nonverbal ability scores occurred at a significantly higher rate than in the DAS normative sample (30%) in both a younger group of 73 children (56%) with a mean age of 5;5 and an older group of 47 children (62%) with a mean age of 8;11. Discrepancies were mainly in favor of nonverbal ability in the younger group, but occurred equally in favor of verbal and nonverbal abilities in the older group. Comparison of the two age groups suggested a growing dissociation between verbal and nonverbal (and particularly visual processing) skills with age. In the older group, children with discrepantly higher nonverbal abilities demonstrated significantly greater impairment in social functioning, as measured on the ADOS, independent of absolute level of verbal and overall ability.
Conclusions
These findings demonstrate a high rate of uneven cognitive development in children with ASD. Indications of a dissociation between verbal and visual-perceptual skills among the older children, and the specific association of discrepantly high nonverbal skills with increased social symptoms suggest that the nonverbal > verbal profile may index an etiologically significant subtype of autism.
PMCID: PMC1201493  PMID: 12236615
Autistic disorder; behavioral phenotypes; cognition; individual differences; intelligence; symptomatology; ADI-R: Autism Diagnostic Interview - Revised; ADOS: Autism Diagnostic Observation Schedule; ASD: autism spectrum disorder; DAS: Differential Ability Scales; GCA: General Conceptual Ability; NV: Nonverbal; PDDNOS: Pervasive Developmental Disorder Not Otherwise Specified; V: Verbal
17.  Maternal Functional Speech to Children: A Comparison of Autism Spectrum Disorder, Down Syndrome, and Typical Development 
Children with developmental disabilities benefit from their language environment as much as, or even more than, typically developing (TD) children, but maternal language directed to developmentally delayed children is an under investigated topic. The purposes of the present study were to compare maternal functional language directed to children with two developmental disabilities – Autism Spectrum Disorder (ASD) and Down Syndrome (DS) –with TD children and to investigate relations of maternal functional language with child language skills. Participants were 60 mothers and their children with TD (n =20), DS (n =20), or ASD (n =20). Children’s mean developmental age was 24.77 months (SD = 8.47) and did not differ across the groups. Mother and child speech were studied during naturalistic play. We found (a) similarities in maternal functional language directed to the two groups of children with developmental disabilities compared to that directed to TD children and (b) a positive association between subcategories of information-salient speech and child mean length of utterance in TD dyads only. The clinical and developmental implications of these findings are discussed.
doi:10.1016/j.ridd.2011.10.018
PMCID: PMC3429128  PMID: 22119699
18.  High Prescription Drug Utilization and Associated Costs among Medicaid-eligible Children with Autism Spectrum Disorders Identified by a Population-based Surveillance Network 
Annals of epidemiology  2012;22(1):1-8.
Purpose
This study assessed medication use and associated costs among 8- and 15-yearold children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network.
Methods
All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n=263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder- not otherwise specified (PDD-NOS) were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data.
Results
All 263 SCADDM-identified children had Medicaid data available; 56% (n=147) had a prescription of any type, 40% (n=105) used psychotropic medication, and 20% (n=52) used multiple psychotropic classes over the study period. Common combinations were (1) attention deficit hyperactivity disorder (ADHD) medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age.
Conclusions
Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age.
doi:10.1016/j.annepidem.2011.10.007
PMCID: PMC3240812  PMID: 22153288
Autism; Psychotropic Medication; Medicaid; Public Health Surveillance
19.  Parents of children with autism spectrum disorder and children with intellectual disabilities and their stress and general health 
Introduction
The negative impact on mother’s well-being of having a child with developmental disabilities is well established in Western societies. By contrast less research has been undertaken in other cultures or with fathers.
Method
A convenience sample of 91 parents was recruited in Tehran: 50 parents of children with intellectual disabilities and 41 parents of children with autism spectrum disorder (ASD). A Farsi translation of two widely used scales—general health questionnaire (GHQ) and parental stress index—was used to gauge parental well-being.
Results
Mothers had significantly higher scores than fathers on the GHQ and had higher levels of child-related stress. Also, both mothers and fathers of younger children tended to have significantly higher stress scores, same goes for parents whose children had ASD.
Conclusion
Hence in Middle Eastern countries such as Iran, mothers in particular face stress and health problems as a consequence of caring for a child with developmental disabilities and these seem to be more marked when the child has ASD.
Discussion
Further research is needed with fathers around their decreased involvement with the affected child and cultural expectations that fathers should be able to cope. These findings may also have implications for carers of older persons in non-Western societies.
PMCID: PMC2707573
autism spectrum disorder; intellectual disabilities; parental stress; parental general health; Iran
20.  Mothers’ Reports of Play Dates and Observation of School Playground Behavior of Children Having High-Functioning Autism Spectrum Disorders 
Background
Children with high functioning autism spectrum disorders (ASD) are generally included with typically developing peers at school. They have difficulties interacting with peers on the school play ground. Previous literature suggests that having play dates in the home may be related to better peer acceptance at school.
Methods
This study examines the relationship between mother-reported play date frequency and amount of conflict, and peer interaction observed on the school playground for a sample of 27 boys and 4 girls meeting structured interview and observation criteria for ASD. Measures of intellectual functioning, adaptive behavior, and social skills were included in a stepwise regression analysis to account for their impact on relationships between maternal play date reports, general peer acceptance at school (as rated by the child’s teacher) and observations of school playground behavior.
Results
Results revealed that children with autism spectrum disorders who had more play dates in their home tended to spend a greater amount of time engaged in behaviors such as mutual offering of objects, conversing and other turn taking activities with peers on the school playground. They also received more positive responses to their overtures from peers. These relationships remained highly significant even after accounting for other demographic, general social, and cognitive variables.
Conclusions
The present results suggest that play date frequency is strongly related to school playground behavior. Due to the design of this study, future research must assess whether play dates in the home promote better peer relationships on the playground or the reverse. In either case, the assessment of play dates, as well as observation of spontaneous unsupervised social interactions are important outcome measures to consider in social skills interventions for children with high functioning ASD.
doi:10.1111/j.1469-7610.2010.02318.x
PMCID: PMC3010494  PMID: 20860756
Social Skills; Autism; Asperger’s Disorder; Friendship
21.  Anxiety in Children and Adolescents with Autism Spectrum Disorders 
Clinical psychology review  2009;29(3):216-229.
Anxiety and poor stress management are common concerns in clinical samples of children with autism spectrum disorders (ASD). Anxiety may worsen during adolescence, as young people face an increasingly complex social milieu and often become more aware of their differences and interpersonal difficulties. This review summarizes the state of research on the prevalence, phenomenology, and treatment of anxiety in youth with autism and related conditions such as Asperger’s disorder. Using search words autism, asperger(s), or pervasive developmental disorder and anxiety or anxious to find reports published between 1990 and 2008, this review identified 40 papers. The results of the review suggest that anxiety, whether measured categorically or dimensionally, is indeed common in children and adolescents with autism spectrum disorders and may be a source of additional morbidity. The assessment of anxiety disorders in ASD should be conducted using multiple informants and modalities, as children with ASD often do not display age-typical symptoms of anxiety. To date, relatively few controlled intervention studies using well-characterized samples have been conducted despite preliminary evidence for efficacy of select pharmacological and psychosocial approaches. Recommendations for future applied research are presented and clinical implications are explored.
doi:10.1016/j.cpr.2009.01.003
PMCID: PMC2692135  PMID: 19223098
Autism; Asperger’s Disorder; anxiety
22.  Factors Associated With Age of Diagnosis Among Children With Autism Spectrum Disorders 
Pediatrics  2005;116(6):1480-1486.
Objective
Early diagnosis of children with autism spectrum disorders (ASD) is critical but often delayed until school age. Few studies have identified factors that may delay diagnosis. This study attempted to identify these factors among a community sample of children with ASD.
Methods
Survey data were collected in Pennsylvania from 969 caregivers of children who had ASD and were younger than 21 years regarding their service experiences. Linear regression was used to identify clinical and demographic characteristics associated with age of diagnosis.
Results
The average age of diagnosis was 3.1 years for children with autistic disorder, 3.9 years for pervasive developmental disorder not otherwise specified, and 7.2 years for Asperger’s disorder. The average age of diagnosis increased 0.2 years for each year of age. Rural children received a diagnosis 0.4 years later than urban children. Near-poor children received a diagnosis 0.9 years later than those with incomes >100% above the poverty level. Children with severe language deficits received a diagnosis an average of 1.2 years earlier than other children. Hand flapping, toe walking, and sustained odd play were associated with a decrease in the age of diagnosis, whereas oversensitivity to pain and hearing impairment were associated with an increase. Children who had 4 or more primary care physicians before diagnosis received a diagnosis 0.5 years later than other children, whereas those whose pediatricians referred them to a specialist received a diagnosis 0.3 years sooner.
Conclusion
These findings suggest improvements over time in decreasing the age at which children with ASD, especially higher functioning children, receive a diagnosis. They also suggest a lack of resources in rural areas and for near-poor families and the importance of continuous pediatric care and specialty referrals. That only certain ASD-related behaviors, some of which are not required to satisfy diagnostic criteria, decreased the age of diagnosis suggests the importance of continued physician education.
doi:10.1542/peds.2005-0185
PMCID: PMC2861294  PMID: 16322174
23.  Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms 
Background
Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.
Methods
Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.
Results
There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.
Conclusion
Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.
doi:10.1186/1753-2000-2-4
PMCID: PMC2276205  PMID: 18237439
24.  A systems biological study on the comorbidity of autism spectrum disorders and bipolar disorder 
Bioinformation  2011;7(3):102-106.
Autism Spectrum Disorder (ASD) is a “spectrum” of disorders, characterized by varying degrees of symptoms ranging from mild to severe. Among Psychiatric disorders, Autism Spectrum Disorders have the strongest evidence for a genetic basis, yet the search for specific genes contributing to these often devastating developmental syndromes has proven extraordinarily difficult. Bipolar Disorder (BP) is a manic-depressive disorder whose symptoms are characterized by extremities in moods. It is also called as the “Mood disorder”. BP, like, ASD also has a strong genetic basis and identification of the candidate genes still remains an ongoing effort. Literature studies point to the hypothesis that ASD and BP have good chances of comorbidity and that they may share common pathways for their manifestation. But this hypothesis has not been worked on in depth. Thus, the study focuses on identifying the chances of their comorbidity by identifying their common pathways and the genes involved in the pathways and also discuss the degree of chances of their comorbidity based on the genes involved in the common pathways. Networks for the genes are also constructed to represent their commonness or uniqueness for the disorders.
PMCID: PMC3218309  PMID: 22125377
Autism Spectrum Disorders; Bipolar Disorder; Comorbidity; Systems Biology; Gene Networks
25.  Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study 
Molecular Autism  2011;2:13.
Background
Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.
Methods
Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.
Results
Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.
Conclusion
The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.
doi:10.1186/2040-2392-2-13
PMCID: PMC3170586  PMID: 21810230

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