The broad autism phenotype predicts child functioning in autism spectrum disorders

Background

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).

Methods

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.

Results

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.

Conclusions

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.     

Plasma Oxytocin in Children with Autism and Its Correlations with Behavioral Parameters in Children and Parents

Objective

Oxytocin (OT) has been implicated to play an important role in autism spectrum disorders (ASD) etiology. We aimed to find out the differences in plasma OT levels between children with autism and healthy children, the associations of OT levels with particular autism symptoms and the associations of particular parental autistic traits with their ASD children OT levels.

Methods

We included 19 boys with autism and 44 healthy age-matched boys. OT levels were analyzed by ELISA method. Children with autism were scored by Childhood Autism Rating Scale and Autism Diagnostic Interview (ADI), adjusted research version. Autism Spectrum Quotient (AQ), Systemizing Quotient (SQ) and Empathizing Quotient were completed by parents of children with autism.

Results

Children with autism had significantly lower plasma OT levels than controls. OT levels positively correlated with ADI Reciprocal Interaction and Communication scores. AQ and SQ of fathers positively correlated with children plasma OT level.

Conclusion

Our results support the hypothesis of OT deficiency in autism. The "paradoxical" associations of OT levels and social skills in children with autism indicate disturbances at various levels of OT system. We first reported associations of OT levels in children with autism and behavioral measures in fathers indicating that OT abnormalities stay between parental autistic traits and autism symptoms in their children.     

Psychological adjustment and sibling relationships in siblings of children with Autism Spectrum Disorders: Environmental stressors and the Broad Autism Phenotype

Research with siblings of children with Autism Spectrum Disorders (ASD) suggests that they may be at increased risk for behavioural and emotional problems and relatively poor sibling relationships. This study investigated a diathesis-stress model, whereby the presence of Broad Autism Phenotype features in the typically developing siblings might interact with family-environmental risk variables to predict sibling functioning (5-17 years of age) of children with an Autism Spectrum Disorder (ASD), their child with an ASD, and their own psychological well-being. Sibling adjustment was associated with the extent of behaviour problems in the child with an ASD and with the extent of the sibling's Broad Autism Phenotype (BAP) features. Sibling relationships were more negative when the child with an ASD had more behaviour problems and when there was evidence of critical expressed emotion in the family environment. Siblings with more BAP features, who had brothers/sisters with an ASD and a greater number of behaviour problems, had more behaviour problems themselves. Siblings with more BAP features who had parents with mental health problems reported more sibling relationship conflict.     

The Broad Autism Phenotype Questionnaire

The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the BAP in adults, the Broad Autism Phenotype Questionnaire (BAPQ), was administered to 86 parents of autistic individuals and 64 community control parents. Sensitivity and specificity of the BAPQ for detecting the BAP were high (>70%). Parents of children with autism had significantly higher scores on all three subscales: aloof personality, rigid personality, and pragmatic language. This instrument provides a valid and efficient measure for characterizing the BAP.     

Examining associations between anxiety and cortisol in high functioning male children with autism

Background

Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal.

Methods

Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol).

Results

Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism.

Conclusions

Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances.     

Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder

Objective

Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism.

Method

Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen’s.

Results

In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106) = 6.095; p < .05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106) = 4.068, p = .046; F(1, 106) = 4.068, p = .046; F(1, 106) = 6.064, p = .016).

Conclusion

According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children.     

Predictors of Mental Health in Chinese Parents of Children with Autism Spectrum Disorder (ASD)

The aim of this study was to explore the influence of parental intolerance of Uncertainty (IU), sensory sensitivity (SS) and Broader Autism Phenotype (BAP), as well as the severity of their children’s autism symptoms and co-morbid symptoms, on the mental health of Chinese parents of children with autism spectrum disorder (ASD). One hundred and twenty-two parents (86.9% mothers; M _age = 35.64 years, SD?=?4.21) of children with ASD took part. Regression and mediation analyses showed that children’s internalizing difficulties, parental BAP and IU had a direct effect, and SS had an indirect effect through IU, on parental mental health. We did not find a significant relationship between parental mental health and children’s ASD severity. Our findings emphasise the need to focus on parental traits when considering their well-being and mental health, and have implications for the design of evidence-based services to support the needs of parents.     

Variable cortisol circadian rhythms in children with autism and anticipatory stress

Objective

Autism is characterized by impairment in communication and social interaction, by repetitive behaviours and by difficulty in adapting to novel experiences. The objective of the current investigation was to replicate and extend our previous findings showing variable circadian rhythm and significant elevations in cortisol following exposure to a novel stimulus (mock magnetic resonance imaging [MRI]).

Methods

Circadian rhythms of cortisol were estimated in 22 children with and 22 children without autism via analysis of salivary samples collected in the morning, afternoon and evening over 6 separate days. We assessed hypothalamic-pituitary-adrenal (HPA) responsiveness by examining changes in salivary cortisol in response to a mock MRI. One-half of the children were re-exposed to the MRI environment.

Results

Children with autism showed a decrease in cortisol in the morning over 6 days while maintaining higher evening values. Children with autism also showed more within-and between-subject variability in circadian rhythms. Although the cortisol values tended to be higher in some of the children with autism, a statistically significant elevation in cortisol in response to the initial mock MRI was not observed. Rather, both groups showed heightened cortisol at the arrival to the second visit to the imaging centre, suggesting an anticipatory response to the re-exposure to the mock MRI.

Conclusion

Children with autism showed dysregulation of the circadian rhythm evidenced by variability between groups, between children and within individual child comparisons. Both groups demonstrated increased salivary cortisol in anticipation of re-exposure to the perceived stressor.Medical subject headings: autistic disorder, cortisol, circadian rhythm, stress     

Multiple Informant Agreement of Child,Parent, and Teacher Ratings of Child Anxiety Within Community Samples

Objective:

Extant research concerning the degree of multiple informant (that is, parent, clinician, teacher, and child) agreement for child anxiety ratings generally uses clinical samples, and results have been mixed.

Method:

Our study used a community sample of public school children (n = 1039) to investigate child (self), parent, and teacher reports of child anxiety across 3 time points (pretreatement, posttreatment, and follow-up) in 3 independent school prevention and intervention trials.

Results:

Results showed that parents and teachers had high informant agreement for ratings on anxiety across the 3 time points (r = 0.95 to 0.96, P < 0.001); agreement between parent and child (self) reports and between teacher and child (self) reports consistently showed lower agreement across the 3 time points (r = 0.14 and 0.28, respectively, P < 0.001). Group differences were also significant for sex and grade, whereby females more commonly self-reported higher anxiety and children in grades 3 and 4 self-reported higher anxiety, compared with students in grades 5 to 7.

Conclusion:

Correlations between parent and teacher with child ratings were poor over 3 time points, and significant differences were found for sex and grade. Research is needed to understand reasons for poor concordance between parent, child, and teacher ratings of anxiety for all children.     

A molecular genetic study of autism and related phenotypes in extended pedigrees

Background

Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD.

Methods

We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior.

Results

Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas ''repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study.

Conclusions

These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD.     

Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection

The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the Broad Autism Phenotype Questionnaire (BAPQ), Social Responsiveness Scale: Adult Research Version (SRS:ARV), and Family History Interview (FHI) in a large, multi-site study of 1,650 simplex families (Simons Simplex Collection). Correlations between the BAPQ and SRS:ARV Total scores were moderate, and correlations between FHI ratings and SRS:ARV and BAPQ were significant but weak. Overall, the results suggested that BAP traits occur at low rates in simplex families, and rates vary significantly depending upon the measure utilized. Implications include the need for multiple informants, and the assessment of distinct BAP traits in large-scale genetic studies of individuals with ASD.     

Reading the mind in the face and voice in parents of children with Autism Spectrum Disorders

One core feature of Autism Spectrum Disorders (ASD) is impairment in social functioning and inferring mental states and emotions referred to theory of mind (TOM). The “Broad Autism Phenotype” (BAP) proposes that defining features of autism express in milder form among first degree relatives of these patients. Theory of mind deficits has been examined using advanced TOM tasks such as “Reading the Mind in the Eyes”. This study has furthered previous findings using another test designed to tap higher TOM abilities named “Mind Reading in the Voice”. The objective of this study is to examine theory of mind abilities from two main communicative sources in parents of children with ASD in contrast to two groups, one clinical and one non-clinical. Forty-eight parents of individuals with autism, 31 parents of individuals with Down syndrome and 30 parents of typically developed children were administered two tests of mind-reading. Analysis revealed that although there is not a significant difference between three groups’ performance in “Mind Reading from Eyes”, parents of children with ASD have significantly lower performance in “Mind Reading from Voice”. It can be concluded that TOM deficits in parents of children with ASD are not restricted to inferring mental states form eyes and deficits in mind-reading from voice could also be a part of BAP.     

L’enfant autiste et son parent face à l’échec de l’intersubjectivité : une clinique de la narrativité

Aim

This article examines the failure of the processes enabling access to intersubjectivity and to primary subjectivation in the treatment of small children presenting autism, and the consequences thereof in the development of parenting exercised by the mothers and fathers of such children. The psychotherapeutic processes implemented via narrative and testimonial functions during consultations appear necessary to relaunch narrative identity and the capacity for parental reverie.

Behavioral,cognitive, and adaptive development in infants with autism spectrum disorder in the first 2?years of life

Background

To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR).

Methods

Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg).

Results

The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains.

Conclusions

These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9117-6) contains supplementary material, which is available to authorized users.     

Autistic children,their parents,and the failures of intersubjectivity: A narrative approach

Aim

This article examines the failure of the processes of access to intersubjectivity and to primary subjectivation in the treatment of young children presenting autism, and the consequences thereof for the development of parenthood. The psychotherapeutic nature of certain narrative and testimonial processes used during parent-child consultations appears as a critical element in the restarting of narrative identity and of the capacity for parental reverie.

Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome

Background

Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism.

Methods

Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised.

Results

For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes.

Conclusions

These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder.     

Testing a Model of Sexual Minority Orientation in Individuals with Typical Development,the Broad Autism Phenotype,and Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Individuals with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP) are more likely than individuals with typical development (TD)...     

Testing for association of the monoamine oxidase A promoter polymorphism with brain structure volumes in both autism and the fragile X syndrome

Background

Autism and the fragile X syndrome (FXS) are related to each other genetically and symptomatically. A cardinal biological feature of both disorders is abnormalities of cerebral cortical brain volumes. We have previously shown that the monoamine oxidase A (MAOA) promoter polymorphism is associated with cerebral cortical volumes in children with autism, and we now sought to determine whether the association was also present in children with FXS.

Methods

Participants included 47 2-year-old Caucasian boys with FXS, some of whom also had autism, as well as 34 2-year-old boys with idiopathic autism analyzed in a previous study. The MAOA promoter polymorphism was genotyped and tested for relationships with gray and white matter volumes of the cerebral cortical lobes and cerebro-spinal fluid volume of the lateral ventricles.

Results

MAOA genotype effects in FXS children were the same as those previously observed in idiopathic autism: the low activity MAOA promoter polymorphism allele was associated with increased gray and white matter volumes in all cerebral lobes. The effect was most pronounced in frontal lobe gray matter and all three white matter regions: frontal gray, F = 4.39, P = 0.04; frontal white, F = 5.71, P = 0.02; temporal white, F = 4.73, P = 0.04; parieto-occipital white, F = 5.00, P = 0.03. Analysis of combined FXS and idiopathic autism samples produced P values for these regions <0.01 and effect sizes of approximately 0.10.

Conclusions

The MAOA promoter polymorphism is similarly associated with brain structure volumes in both idiopathic autism and FXS. These data illuminate a number of important aspects of autism and FXS heritability: a genetic effect on a core biological trait of illness, the specificity/generalizability of the genetic effect, and the utility of examining individual genetic effects on the background of a single gene disorder such as FXS.     

Perinatal and Familial Risk Factors Are Associated with Full Syndrome and Subthreshold Attention-Deficit Hyperactivity Disorder in a Korean Community Sample

Objective

The objective of this study was to examine the effect of perinatal and familial risk factors on full syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD) among Korean children and adolescents.

Methods

A sample of 2,673 students was randomly selected from 19 representative schools in Seoul, Korea. The parents of the students completed the Diagnostic Interview Schedule for Children-version IV (DISC-IV), as well as questionnaires on perinatal and familial risk factors.

Results

Maternal stress and alcohol use during pregnancy, parental marital discord, parental separation or divorce, changes in primary caregivers, and notbreastfeeding were significantly associated with full syndrome ADHD; however, maternal stress during pregnancy was the only variable that differentiated subthreshold ADHD from non-ADHD.

Conclusion

Our results provide evidence the perinatal and familial risk factors contribute to the development of ADHD in Korea children and adolescents, and suggest that these perinatal and familial risk factors are more closely related to full syndrome than to subthreshold ADHD.