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.
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.
Autism; Asperger’s disorder; psychiatric comorbidity; anxiety; depression; mood disorders; familial aggregation; maternal symptoms
To compare scores on autism spectrum disorder (ASD) symptom scales in healthy youths and youths with mood or anxiety disorders.
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.
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.
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.
mood disorder; anxiety disorder; autism spectrum; impairment
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.
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.
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).
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.
Autistic disorder; Child; Iran; Parents
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.
autism; co-morbidity; psychiatric disorders; adolescents and adults; burden
Objectives. To analyze cooccurring disorders and problems in a representative group of 198 preschool children with autism spectrum disorders (ASD) who had had interventions at a specialized habilitation center. Methods. Parents and children were seen by a research team. Data were based on parental interviews, pediatric assessments, and tests of the child. Information on autistic symptoms, general cognitive function, speech and language, motor function, epilepsy, vision, hearing, activity level, behavior, and sleep was collected. Results. Three ASD categories were used: (1) autistic disorder (AD), (2) autistic-like condition (ALC) or Asperger syndrome, and (3) one group with autistic symptoms/traits but not entirely all its criteria met for ASD. Children with autism had a mean of 3.2 coexisting disorders or problems, the ALC/Asperger group had a mean of 1.6, and children with autistic traits had a mean of 1.6. The most common disorder/problems in the total group pertained to language problems (78%), intellectual disability (ID) (49%), below average motor function (37%), and severe hyperactivity/ADHD (33%). Conclusions. The results accord with the concept of early symptomatic syndromes eliciting neurodevelopmental clinical examination (ESSENCE), and highlight the need of considering ASD in a broad perspective taking also other cooccurring developmental disorders into account.
Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger Syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl- (penta) and copro- porphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and copro porphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (p < 0.006) and copro (p < 0.006) concentrations compared to same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic (ROC) curve analysis, we evaluated the sensitivity and specificity of penta, copro and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic.
autistic spectrum disorder; porphyrins; heme; biomarker; children
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.
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
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.
Autism; Risk; Parenting; Parent-Child Interaction; Sensitivity; Language
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.
siblings; autism spectrum disorder; maternal well-being; depression
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.
Asperger; Aripiprazole; Obsessive compulsive disorder
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.
Autism; genetics; mental handicap
Autism spectrum disorders (ASDs) are neurodevelopmental in origin, affecting an estimated 1 in 88 children in the United States. We previously described ASD-specific maternal autoantibodies that recognize fetal brain antigens. Herein, we demonstrate that lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2) and Y-box-binding protein to comprise the seven primary antigens of maternal autoantibody-related (MAR) autism. Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of ASD children and only 1% of controls. ASD children from mothers with specific reactivity to LDH, STIP1 and CRMP1 and/or cypin (7% vs 0% in controls; P<0.0002; odds ratios of 24.2 (95% confidence interval: 1.45–405)) had elevated stereotypical behaviors compared with ASD children from mothers lacking these antibodies. We describe the first panel of clinically significant biomarkers with over 99% specificity for autism risk thereby advancing our understanding of the etiologic mechanisms and therapeutic possibilities for MAR autism.
autism; autoantibodies; fetal brain; neurodevelopment
Parents of children with autism spectrum disorders (ASDs) are at risk for higher stress levels than parents of children with other developmental disabilities and typical development. Recent advances in early diagnosis have resulted in younger children being diagnosed with ASDs but factors associated with parent stress in this age group are not well understood.
The present study examined parenting-related stress and psychological distress in mothers of toddlers with ASD, developmental delay without ASD (DD), and typical development. The impact of child problem behavior and daily living skills on parenting-stress and psychological distress were further investigated.
Participants were part of a larger research study on early ASD intervention. Parent self-report of parenting-related stress and psychological distress was utilized.
Parents of toddlers with ASD demonstrated increased parenting-related stress compared with parents of toddlers with DD and typical development. However, psychological distress did not differ significantly between the groups. Child behavior problems, but not daily living skills emerged as a significant predictor of parenting-related stress and psychological distress. This was true for both mothers of children with ASD and DD.
These finding suggest that parents’ abilities to manage and reduce behavior problems is a critical target for interventions for young children with ASD and DD in order to improve child functioning and decrease parenting-related stress.
Autism Spectrum Disorder; parents; distress; toddlers; parenting-stress
We analyzed data from case groups of 538 children with autism spectrum disorders (ASD) and 163 with developmental delays (DD), and from 421 typically developing controls to assess associations with maternal influenza or fever during pregnancy. Exposure information was obtained by telephone interviews, and outcomes were clinically confirmed. Though neither ASD nor DD was associated with influenza, both were associated with maternal fever during pregnancy: OR’s (odds ratios) were 2.12 (95 % CI 1.17, 3.84) and 2.50 (95 % CI 1.20, 5.20) respectively. However, the fever-associated ASD risk was attenuated among mothers who reported taking antipyretic medications (OR = 1.30, 95 % CI 0.59, 2.84), but remained elevated for those who did not (OR = 2.55, 95 % CI 1.30, 4.99).
Maternal influenza; Fever; Autism; Anti-fever medication
The prevalence of sleep related complaints is reported by questionnaire studies to be as high as 83.3% in children with autism spectrum disorders (ASD). Questionnaire studies report the presence of various parasomnia in ASD. However, no polysomnographic study reports non-REM parasomnias and only a single study reports REM related parasomnias in ASD. We investigated the prevalence and characteristics of sleep disorders by polysomnographic study and questionnaires in a cohort of 23 children with ASD and 23 age-matched children of a non-autistic comparison group. The results showed significantly more non-REM parasomnias in 14 children with ASD on polysomnograms (PSG) and 16 ASD children by questionnaire, a finding that was not associated with medication use, other comorbid medical or psychiatric disorders, or sleep disordered breathing. Of the 14 children with ASD who had PSG evidence of parasomnia, 11 of them had a history suggestive of parasomnia by questionnaire. There was a high sensitivity but a low specificity of parasomnia in ASD by questionnaire in predicting the presence of parasomnia in the PSG. Of the parasomnias recorded in the laboratory, 13 ASD children had Disorders of Partial Arousal, consistent with sleep terrors or confusional arousals. Furthermore, multiple episodes of partial arousal occurred in 11 of the 13 ASD children who had PSG evidence of Disorders of Partial Arousal. Of the 11 ASD children with multiple episodes of partial arousal, 6 ASD children had multiple partial arousals during both nights’ PSG study. Sleep architecture was abnormal in children with ASD, characterized by increased spontaneous arousals, prolonged REM latency and reduced REM percentage. These results suggest a high prevalence of parasomnia in this cohort of children with ASD and a careful history intake of symptoms compatible with parasomnia could be prudent to diagnose parasomnia in ASD children when performing a PSG is not possible.
Autism spectrum disorders; parasomnia; sleep terror; confusional arousal; disorders of partial arousal
The purpose of this study was to compare a medical diagnosis of autism spectrum disorder (ASD) with the perceptions of immigrant parents regarding their child’s difficulties.
Semistructured interviews were conducted with parents. The children were assessed using the ADOS, and a multiaxial diagnosis was reached using the DSM-IV.
The majority of parents recognized symptoms in their child that were related to autism. Less often, however, parents believed their children had a developmental delay or communication problem rather than an ASD. There were also parents who failed to see any problem at all in their child although the child was, nonetheless, diagnosed as having an ASD.
The failure of immigrant mothers to acknowledge a diagnosis of ASD in their younger children may represent an attempt to preserve hope for their child’s future. Mothers of older children may not, however, agree with the psychiatric diagnosis. Community services need to balance the need to convey accurate medical information with the need to protect parents’ investment in their children. This may be particularly true for immigrant parents who are living outside their cultural framework.
autism; diagnosis; parents; immigrant; perceptions; qualitative; autisme; diagnostic; parents; immigrants; perception; qualitatif
The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets.
Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD.
Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9).
Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.
Autism; Bayesian; Imidacloprid; Measurement error; Neonicotinoids; Pesticides
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.
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.
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.
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.
Genetics; Pervasive Developmental Disorder; Language; Broader Autism Phenotype
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.
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.
Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connection. We hypothesized that in families affected by ASD, elevated maternal and paternal BAPQ scores would correlate with greater autism symptomatology in diagnosed children. In an extension of prior research, we also explored this relationship in families with typically developing children (TDC).
Two hundred and forty-five children with ASD, 129 TDC and all parents were recruited as part of a larger study investigating relationships between genes, brain and behavior. The Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and expert clinical judgment confirmed ASD diagnoses in children. SRS was collected for all children. Parents completed a self-report BAPQ and an informant report BAPQ for their spouse; an average of self-report and informant report for each parent was used in all analyses.
Mothers and fathers of children with ASD had significantly higher rates of BAP traits as compared to parents of TDC. Maternal and paternal BAPQ total scores were not correlated with child IQ in either group. In the ASD group, 10% of mothers and 21% of fathers scored above the established BAP threshold compared to 4% of TDC parents. Crude regression analyses showed that maternal and paternal BAPQ total scores accounted for significant variance in child SRS scores in both ASD (17.1%) and TDC (19.8%) families.
Our results suggest that broad autism symptomatology in parents is moderately associated with their child’s autism symptomatology. This result extended to TDC families, suggesting that the BAPQ and SRS capture subtle, subclinical social variation in both children and adults. These findings could help define multi-generational social impairments in future phenotypic and genetic studies.
Autism spectrum disorders; Broad autism phenotype; Social functioning
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.
autism; gene; immune; maternal; cytokine
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.
Research findings investigating the sociodemographics of autism spectrum disorder (ASD) have been inconsistent and rarely considered the presence of intellectual disability (ID).
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.
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.
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.