Autism and the broad autism phenotype: familial patterns and intergenerational transmission

Background

Features of the Broad Autism Phenotype (BAP) are disproportionately prevalent in parents of a child with autism, highlighting familial patterns indicative of heritability. It is unclear, however, whether the presence of BAP features in both parents confers an increased liability for autism. The current study explores whether the presence of BAP features in two biological parents occurs more frequently in parents of a child with autism relative to comparison parents, whether parental pairs of a child with autism more commonly consist of one or two parents with BAP features, and whether these features are associated with severity of autism behaviors in probands.

Method

Seven hundred eleven parents of a child with an autism spectrum disorder and 981 comparison parents completed the Broad Autism Phenotype Questionnaire. Parents of a child with autism also completed the Social Communication Questionnaire.

Results

Although parental pairs of a child with autism were more likely than comparison parental pairs to have both parents characterized by the presence of the BAP, they more commonly consisted of a single parent with BAP features. The presence of the BAP in parents was associated with the severity of autism behaviors in probands, with the lowest severity occurring for children of parental pairs in which neither parent exhibited a BAP feature. Severity did not differ between children of two affected parents and those of just one.

Conclusions

Collectively, these findings indicate that parental pairs of children with autism frequently consist of a single parent with BAP characteristics and suggest that future studies searching for implicated genes may benefit from a more narrow focus that identifies the transmitting parent. The evidence of intergenerational transmission reported here also provides further confirmation of the high heritability of autism that is unaccounted for by the contribution of de novo mutations currently emphasized in the field of autism genetics.     

Autism and phenylketonuria

Phenylketonuria (PKU) has been also reported in children with infantile autism (IA); however, the frequency of this association is variably reported. Patients with various forms of hyperphenylalaninemia (HPA) were evaluated applying two methods: the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS). A total of 243 patients were investigated, 97 with classical PKU, 62 identified by neonatal screening, and 35 late diagnosed. None out of 62 patients with classic PKU diagnosed early met criteria for autism. In the group of 35 patients diagnosed late, two boys (5.71%) ages 16 and 13 years fulfilled the diagnostic criteria for autism. The present study confirms that classical PKU is one of the causes of autism, but the prevalence seems to be very low.     

Chromosomal Disorders and Autism

Many cases of autism appear to be caused by several abnormal genes acting in concert. The literature on chromosomal aberrations in autism is reviewed, with a view to finding potential gene markers for the neuropsychiatric disorder. Most of the chromosomes have been implicated in the genesis of autism. However, aberrations on the long arm of Chromosome 15 and numerical and structural abnormalities of the sex chromosomes have been most frequently reported. These chromosomes appear to hold particular promise in the search for candidate genes.     

Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) Correspondence and Conflicts with DSM-IV Criteria in Diagnosis of Autism

Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) are tests widely used for screening and diagnosis of autism. This study verified their correspondence and conflict with a diagnosis made with DSM-IV criteria. The sample consisted of 65 children, aged 18 months to 11 years. We found complete agreement between DSM-IV and CARS. We show that ABC does not distinguish individuals with autistic disorders from other cases of developmental disorders as well as CARS: the number of false negatives is high (46%) with ABC as opposed to 0% with CARS.     

Autism in visually impaired individuals

The aim of the present study was to assess the prevalence and associated risk factors of autism in a sample of visually impaired children and adolescents. A total of 257 blind children and adolescents (age range: 7-18 years) were examined for autism using a three-stage process. The first stage estimated probable cases of autistic disorder based on the Autism Behavior Checklist and the second stage by direct observation of the subjects in different settings. In the third stage, subjects with the probable diagnosis of autistic disorder were asked to undergo psychiatric examination. A final diagnosis of autistic disorder (based on the criteria in DSM-IV) was given after interviewing the caregivers and clinical observation. Thirty of 257 subjects met the criteria for autistic disorder. Comparison of the characteristics of the two groups (autistic and non-autistic) with chi2-squared and independent sample t-tests revealed a statistically significant difference in terms of severity of blindness (P = 0.015), cerebral palsy (P = 0.02) and intellectual level (P = 0.001). The results of the present study suggest that subjects with blindness plus autism have greater neurological impairment (as suggested by the presence of lower intellectual level and cerebral palsy), and more severe visual impairment than the subjects with blindness only.     

Secretin and Autism: A Two-Part Clinical Investigation

Recent anecdotal reports have touted the gastrointestinal (GI) hormone secretin as a treatment modality for autism, though there is little clinical evidence or literature to support its viability. We undertook a two-part clinical trial to investigate these claims. Fifty-six patients (49 boys, 7 girls, mean age = 6.4 years, SD = 2.7) enrolled in an open-label trial of secretin, during which they received one injection of the hormone (2 IU/kg). All subjects were evaluated by their parents at baseline and follow-up visits (3–6 weeks later, M = 3.7, SD = 1.4 weeks) with Childhood Autism Rating Scales (CARS). Thirty-four patients were labeled with Pervasive Developmental Disorder Not Otherwise Specified, and 22 met diagnostic criteria for Autistic Disorder. Forty-five patients were concurrently on other drug treatments. At follow-up, some reported minimal but potentially significant improvements including changes in GI symptoms, expressive and/or receptive language function, and improved awareness and social interactions. No adverse effects were reported or observed. Subsequently, 17 of the most responsive patients from Study 1 began a double-blind trial that also included 8 newly enrolled patients. Patients in this second study were alternatively entered into one of two groups and received injections of secretin or placebo with crossover at 4 weeks. Patients from Study 1 entered into Study 2 at an average of 6.5 (SD = 0.8) weeks after beginning Study 1. Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections.     

Factor Analysis of Restricted and Repetitive Behaviors in Autism Using the Autism Diagnostic Interview-R

The current study examined the factor structure of restricted and repetitive behaviors (RRB) in children with autism. Factor extraction procedures of 12 items from the Autism Diagnostic Interview-Revised (ADI-R) were applied in N = 207 individuals with autism. Two interpretable factors were identified: Factor 1—repetitive sensory motor actions and Factor 2—resistance to change. There was a significant negative correlation between an index of level of adaptive functioning and Factor 1. Intraclass correlations were not significant for either factor in a subset of families with two or more siblings with autism (multiplex). No differences in scores were apparent for either factor when multiplex families and families containing only one affected individual with autism (singleton) were compared. RRB in autism are represented by two distinct factors which may reflect two separate groups within autism. Defining subgroups within autism will allow for reduction of clinical heterogeneity and enhance our ability to dissect the genetic etiology of this complex disorder.     

The Development of Siblings' Understanding of Autism Spectrum Disorders

While professionals commonly advocate sharing information about autism spectrum disorders with siblings, no guidelines currently exist that describe what types of information might be relevant for siblings at different ages. To address this issue, the interviewing method described by Bibace and Walsh (1979, 1980), which measures cognitive sophistication in thinking about illness, was adapted to examine perspectives on autism spectrum disorders. Sixty-three siblings of individuals with autism or related disorders were interviewed using this measure. Parents were given the same interview as their child, and asked to predict their child's responses. Children's reasoning became more mature with age, but developed at a delayed rate compared to norms for illness concepts. Although accurate in estimating their child's understanding of the definition and cause of their sibling' s; diagnosis, parents tended to overestimate their child's understanding of the disorder's impact.     

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.     

The Development of Face Processing in Autism

Both behavioral and neuroimaging evidence indicate that individuals with autism demonstrate marked abnormalities in the processing of faces. These abnormalities are often explained as either the result of an innate impairment to specialized neural systems or as a secondary consequence of reduced levels of social interest. A review of the developmental literature on typical and atypical face processing supports a synthesis of these two hypotheses by demonstrating that face processing is an emergent and developmental skill that is heavily mediated by early experience with faces. Individuals with autism may possess central nervous system irregularities that fail to attribute special status to faces, thereby limiting the visual input required for the development of neural regions specialized for face processing.     

Moderators of Stress in Parents of Children with Autism

Parents of children with autism experience more stress and are more susceptible to negative outcomes than parents of children with other disabilities. The present work examines the relationship between stressors, social support, locus of control, coping styles, and negative outcomes (depression, social isolation, and spousal relationship problems) among parents of children with autism. Fifty-eight parents completed surveys. Results indicated that several coping styles corresponded to negative outcomes. Furthermore, the relationship between stressors and negative outcomes was moderated by social support and coping style. Results are discussed in relation to applications for clinical practice.     

Diagnostic Conceptualization of Autism Among Indian Psychiatrists, Psychologists, and Pediatricians

Diagnostic criteria for autism and background characteristics used by 937 Indian psychiatrists, psychologists and pediatricians were examined. Participants were asked to rate 18 behaviors as necessary for a diagnosis of autism, helpful but not necessary, or not helpful in a diagnosis of autism, and were asked to provide other information about their experiences with autism. Professionals' experience with diagnosing cases did not vary by profession and, in general, the three professions agreed about the characteristics most necessary for a diagnosis. However, within-group differences were found on the agreement over the usefulness of individual characteristics and amount of experience diagnosing cases as autistic. Comparisons with DSM-III and DSM-IV criteria suggest that Indian professionals may adhere to these systems. Conclusions about diagnosis in a cultural context and areas for future research are suggested.     

Autism and developmental delay

Objective This study improves the knowledge of early autistic symptomatology and research concerning (i) the significant differences in the behaviors of children with autistic disorder (AD) and children with a developmental delay (DD), and (ii) the influence of the cognitive delay on symptomatology. Method Two groups of 20 young children (7–42 months) were compared: children with AD, and those with DD. The groups were paired by chronological and developmental age. The comparison was extended to four subgroups composed according to age (younger and older children—<24 months, >24 months) and to the global development quotient (GDQ) (the more and less delayed). Each child was evaluated with the Infant Behavior Summarized Evaluation scale (IBSE). Results For the younger AD children, significant differences affected social communication and their adaptation to the environment (intolerance to frustration, resistance to change). For the older children (>24 months), this study showed the rapid progression of the number of distinctive signs between AD and DD children according to age and/or developmental level. Conclusions Cognitive delay has an important influence on the symptomatology at the moment of initial recognition of an autistic syndrome. This study is a complement for the fuller understanding of the nature and early diagnosis of disorders specific to autism at the earliest phases of development.     

Autism in the Faroe Islands. An Epidemiological Study

The Faroe Islands are considered to be a genetic isolate. This population study of the prevalence of autism sought to identify a representative cohort for future genetic studies. In 2002 all schools were screened for autism spectrum disorders. The target population were all children born in 1985 through 1994 and living in the Faroe Islands on December 31, 2002. Children who screened positive for autism characteristics were examined using the Diagnostic Interview for Social and Communication Disorders (DISCO). Of the children aged 8 through 17 years, 0.56% had childhood autism, Asperger syndrome or atypical autism. The male:female ratio was just under 6:1. The prevalence of autism in the Faroe Islands was very similar to that reported from many western countries.     

Nonverbal Communication Skills in Young Children with Autism

Objective The study was to examine nonverbal communication in young children with autism. Methods The participants were 23 young children with autism (mean CA = 32.79 months), 23 CA and MA-matched children with developmental delay and 22 18–20-month-old, and 22 13–15-month-old typically developing toddlers and infants. The abbreviated Early Social Communication Scales [Mundy et al. 1996, Early social communication scales (ESCS)] were used to test three types of nonverbal communicative skills, i.e., joint attention, requesting, and social interaction. Both frequency and proportion analyses were done in group comparisons. Results (1) Two- to three-year-old children with autism displayed deficits in joint attention ability, especially high-level skills. (2) The deficit in terms of frequency of communication was marked even compared with typically developing infants with younger mental age. (3) Young children with autism had different nonverbal communication profile compared with all three comparison groups. Conclusion Early social-communicative difficulties in autism involve early triadic communications involving joint attention and possibly dyadic turn-taking skills, which has implications for both early screening and early intervention.     

Young Adult Outcome of Autism Spectrum Disorders

To learn about the lives of young adults with ASD, families with children born 1974–1984, diagnosed as preschoolers and followed into adolescence were contacted by mail. Of 76 eligible, 48 (63%) participated in a telephone interview. Global outcome scores were assigned based on work, friendships and independence. At mean age 24, half had good to fair outcome and 46% poor. Co-morbid conditions, obesity and medication use were common. Families noted unmet needs particularly in social areas. Multilinear regression indicated a combination of IQ and CARS score at age 11 predicted outcome. Earlier studies reported more adults with ASD who had poor to very poor outcomes, however current young people had more opportunities, and thus better results were expected.     

Relative Carnitine Deficiency in Autism

A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p=0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.     

Brief Education About Autism Spectrum Disorders for Family Therapists

The prevalence of autism spectrum disorders (ASDs) is on the rise, and family therapists are increasingly likely to encounter clients who have some form of this disorder. There is emerging evidence that professionals, including family therapists, may misdiagnose the condition or that proper diagnosis and treatment may be delayed. Thus, professional education about ASDs is important. In addition to the effects on the diagnosed individual, ASDs have significant impact on the family system. Family-centered interventions constitute a crucial piece of a multifaceted treatment plan, and there is a call for family-centered intervention and support services. To support family therapists in becoming more informed and effective members of treatment teams, this article provides an overview of Asperger's disorder and autism, with a focus on definitions, assessment, and individual treatments of ASDs. Ways in which ASDs have impact on the family are then identified, and specific issues relevant to family treatment are discussed.