fMRI tracks reductions in repetitive behaviors in autism: two case studies.

Autism is characterized by abnormal prefrontal brain activation during cognitive control, a potential biomarker of repetitive behaviors. In this proof-of-principle study, functional magnetic resonance imaging (fMRI) was used to examine brain activity during an oddball task in two high-functioning males with autism before and after 12 weeks of treatment with citalopram, a selective serotonin reuptake inhibitor. One participant showed marked reductions in repetitive behaviors whereas the other showed mild worsening. Brain activation in relevant prefrontal regions increased in only the participant whose repetitive behavior symptoms improved. These findings suggest that fMRI may elucidate potential mechanisms of action of targeted autism interventions.

Age-related differences in restricted repetitive behaviors in autism spectrum disorders.

Restricted repetitive behaviors (RRBs) were examined in a large group of children, adolescents and adults with ASD in order to describe age-related patterns of symptom change and association with specific contextual factors, and to examine if the patterns of change are different for the various types of RRBs. Over 700 individuals with ASD were rated on the Repetitive Behavior Scale-Revised. RRBs were less frequent and less severe among older than younger individuals, corroborating that autism symptoms abate with age. Our findings further suggest that repetitive behaviors are a heterogeneous group of behaviors, with the subtypes of RRBs having their own individual patterns across the lifespan, and in some cases, a differential association with age depending on intellectual functioning.

Evidence for three subtypes of repetitive behavior in autism that differ in familiality and association with other symptoms.

BACKGROUND: Restricted repetitive behaviors (RRBs) are a core feature of autism and consist of a variety of behaviors, ranging from motor stereotypies to complex circumscribed interests. The objective of the current study was to examine the structure of RRBs in autism using relevant items from the Autism Diagnostic Interview-Revised in a sample of 316 individuals with autistic disorder. METHODS/RESULTS: Using exploratory factor analysis, three distinct factors were identified: Repetitive Motor Behaviors (RMB), Insistence on Sameness (IS), and Circumscribed Interests (CI). RMB were found to be associated with a variety of subject characteristics such as IQ, age, social/communication impairments, and the presence of regression. IS was associated with social and communication impairments whereas CI appeared to be independent of subject characteristics, suggesting CI may be particularly useful in subsetting samples. Based on sib-pair correlations, IS and CI (but not RMB) appear to be familial. Analysis of the data at the case level suggests that the presence of multiple forms of RRB in an individual is associated with more impairment in the social and communication domains, suggesting a more severe presentation of autistic disorder. CONCLUSIONS: There appears to be considerable structure within repetitive behavior in autism. The finding that these behaviors are differentially related to subject characteristics and familiality adds to their validity.

The Repetitive Behavior Scale-Revised: independent validation in individuals with autism spectrum disorders.

A key feature of autism is restricted repetitive behavior (RRB). Despite the significance of RRBs, little is known about their phenomenology, assessment, and treatment. The Repetitive Behavior Scale-Revised (RBS-R) is a recently-developed questionnaire that captures the breadth of RRB in autism. To validate the RBS-R in an independent sample, we conducted a survey within the South Carolina Autism Society. A total of 320 caregivers (32%) responded. Factor analysis produced a five-factor solution that was clinically meaningful and statistically sound. The factors were labeled "Ritualistic/Sameness Behavior," "Stereotypic Behavior," "Self-injurious Behavior," "Compulsive Behavior," and "Restricted Interests." Measures of internal consistency were high for this solution, and interrater reliability data suggested that the RBS-R performs well in outpatient settings.

Children's Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders.

OBJECTIVE: To examine the psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scales (CYBOCS) modified for pervasive developmental disorders (PDDs). METHOD: Raters from five Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were trained to reliability. The modified scale (CYBOCS-PDD), which contains only the five Compulsion severity items (range 0-20), was administered to 172 medication-free children (mean 8.2 +/- 2.6 years) with PDD (autistic disorder, n = 152; Asperger's disorder, n = 6; PDD not otherwise specified, n = 14) participating in RUPP clinical trials. Reliability was assessed by intraclass correlation coefficient (ICC) and internal consistency by Cronbach's alpha coefficient. Correlations with ratings of repetitive behavior and disruptive behavior were examined for validity. RESULTS: Eleven raters showed excellent reliability (ICC = 0.97). The mean CYBOCS score was 14.4 (+/- 3.86) with excellent internal consistency (alpha = .85). Correlations with other measures of repetitive behavior ranged from r = 0.11 to r = 0.28 and were similar to correlations with measures of irritability (r = 0.24) and hyperactivity (r = 0.25). Children with higher scores on the CYBOCS-PDD had higher levels of maladaptive behaviors and lower adaptive functioning. CONCLUSIONS: The five-item CYBOCS-PDD is reliable, distinct from other measures of repetitive behavior, and sensitive to change.

Neurochemical correlates of autistic disorder: a review of the literature.

Review of neurochemical investigations in autistic disorder revealed that a wide array of transmitter systems have been studied, including serotonin, dopamine, norepinephrine, acetylcholine, oxytocin, endogenous opioids, cortisol, glutamate, and gamma-aminobutyric acid (GABA). These studies have been complicated by the fact that autism is a very heterogeneous disorder which often presents with comorbid behavioral problems. In addition, many of these studies employed very small samples and inappropriate control groups, making it difficult to draw conclusions with confidence. Overall, serotonin appears to have the most empirical evidence for a role in autism, but this requires further investigation and replication. There is little support for the notion that a dysfunction of norepinephrine or the endogenous opioids are related to autism. The role of dopaminergic functioning has not been compelling thus far, though conflicting findings on central dopamine turnover require further study. Promising new areas of study may include possible dysfunction of the cholinergic system, oxytocin, and amino acid neurotransmitters. Implications for pharmacotherapy are briefly discussed for each neurotransmitter system with brief research examples. Review of this work emphasizes the need for future studies to control for subject variables, such as race, sex, pubertal status, and distress associated with blood draws, which can affect measures of neurochemical function. In addition, research in neurochemistry must continue to work in concert with other subspecialties to form a more comprehensive and theory-based approach to the neurobiological correlates of autistic disorder.

Medication patterns in patients with autism: temporal, regional, and demographic influences.

To date, there have been relatively few surveys of psychotropic medicine use in individuals with autism. Data were analyzed from three statewide surveys that employed the same questionnaire and survey methodology. The first was done in the Autism Society of North Carolina in 1992-1993 (NC-1, n = 838; Aman et al. 1995); the second was done in the Autism Society of Ohio in 1999 (Ohio, n = 417; Aman et al. 2003), and the third was done again in the Autism Society of North Carolina in 2001 (NC-2, n = 1538; Langworthy-Lam et al. 2002). Response rates ranged from 48%-56%. Longitudinal trends were examined by comparing the NC-1 and NC-2 data, and regional effects were assessed by comparing the NC-2 and Ohio data. There was a very large increase in antidepressant utilization from 1993 to 2001, with significant increases also occurring for antipsychotics, psychostimulants, and alpha-agonists and beta-blockers. Among youths with autism, the use of any psychotropic increased from 30.5% in NC-1 to 45.2% in NC-2. Psychotropic medication patterns were remarkably consistent across North Carolina and Ohio, except that significantly more autism supplements were used in Ohio. We also examined subject and demographic variables across studies and found several robust correlates of psychotropic medication use. Greater age and handicap, and more restrictive placements, were associated with the use of several drug classes. Knowledge of these patterns may help families and medical planners anticipate future needs.

Prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio.

To date, there have been few surveys of psychotropic and antiepileptic drug (AED) prevalence in individuals with autism-spectrum conditions. We surveyed 747 families in the Autism Society of Ohio regarding the use of psychotropic drugs, AEDs, and over-the-counter (OTC) preparations for autism. In all, 417 families (55.8%) replied. A total of 45.6% were taking some form of psychotropic agent (including St. John's wort and melatonin), whereas 11.5% were taking AEDs, and 10.3% took OTC autism preparations. The most common psychotropic agents included antidepressants (21.6%), antipsychotics (14.9%), antihypertensives (12.5%), and stimulants (11.3%). Some 51.6% were prescribed psychotropic drugs or AEDs, and 55.4% took psychotropic drugs, AEDs, or autism supplements. Demographic variables frequently found to be associated with medication use included greater age, more severe autism, more severe intellectual handicap, and housing outside the family home. Whereas there is empirical support for the use of some of these psychotropic agents in autism, others are being prescribed with minimal research support. OTC autism preparations were used in substantial numbers of individuals, despite limited research support and the possibility of toxic effects.

The broad autism phenotype questionnaire: prevalence and diagnostic classification.

The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n = 1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 14-23% for PCAs and between 5-9% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, 6: 134-143. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Phenomenology and measurement of circumscribed interests in autism spectrum disorders.

Circumscribed interests (CI) are important and understudied symptoms that affect individuals with autism spectrum disorders (ASD). The present study sought to develop quantitative measures of the content, intensity and functional impairment of CI in 50 children with high-functioning ASD compared to an age-, IQ-, and gender-matched sample of 50 typically developing (TD) peers. The Interests Scale, a parent-rating questionnaire, and the Interview for Repetitive Behaviors, a semi-structured interview, were used to assess CI. Groups did not differ on the number of interests children held, but they did differ on types of interests and impairment associated with them. The interests of ASD participants were more likely to be nonsocial in nature (e.g. mechanical systems) than TD participants. Parents of children with ASD endorsed higher degrees of functional impairment on metrics including frequency, interference, resistance when interrupted, flexibility, and accommodation required, as well as less involvement of other people, than parents of children with TD. These findings suggest that interests of individuals with ASD differ qualitatively and in intensity from individuals with TD. The present study offers further support for the notion that CI reflect a clinically significant feature of ASD that warrants intervention in some children.

Performance of children with autism spectrum disorders on the dimension-change card sort task.

Restricted and repetitive behaviors in autism spectrum disorders have been conceptualized to reflect impaired executive functions. In the present study, we investigated the performance of 6-17-year-old children with and without an autism spectrum disorder on a dimension-change card sort task that explicitly indicated sorting rules on every trial. Diagnostic groups did not differ in speed of responses after the first rule switch or in speed or accuracy on blocks with mixed versus single sort rules. However, performance of the ASD group was significantly slower and less accurate overall than the typically-developing group. Furthermore, within the ASD group, poorer DCCS task performance did not predict more severe autism symptoms. Implications for the executive dysfunction theory of autism are discussed.

Generativity abilities predict communication deficits but not repetitive behaviors in Autism Spectrum Disorders.

Individuals with Autism Spectrum Disorders (ASD) often demonstrate impaired generativity that is thought to mediate repetitive behaviors in autism (Turner in J Child Psychol Psychiatry, 40(6):839-849, 1999a). The present study evaluated generativity in children with and without ASD via the use-of-objects task (Turner in J Child Psychol Psychiatry, 40(2):189-201, 1999b) and an Animals Fluency Task (Lezak in Neuropsychological assessment. Oxford University Press, Oxford, 1995). Groups differed significantly on two of four metrics from the Animals Fluency Task and two of seven metrics from the Use of Objects task. In the ASD sample, no significant relations were found between generativity and repetitive behaviors. Significant relations were found, however, between performance on the Animals Fluency Task and communication symptoms. Results replicate reports of generativity deficits in ASD and suggest that impaired generativity may reflect communication deficits that are characteristic of the disorder.

Children with autism demonstrate circumscribed attention during passive viewing of complex social and nonsocial picture arrays.

Although circumscribed interests are a hallmark characteristic of autism spectrum disorders, providing a means for quantifying their functional impairment has proven difficult. We developed a passive viewing task to measure aspects of visual attention in children with autism spectrum disorders and typically developing controls. Task stimuli included picture arrays that were matched for social and nonsocial content. Nonsocial content was balanced to include items related to circumscribed interests (e.g., trains) as well as more commonplace items (e.g., furniture). Discrete aspects of gaze behavior were quantified using eye-tracking technology. Results indicate that visual attention in the autism group was more circumscribed (as indicated by the exploration of fewer images), more perseverative (as indicated by longer fixation times per image explored), and more detail oriented (as indicated by a greater number of discrete fixations on explored images). This pattern of results was similar for both social and object arrays. Within the autism group, overall severity of repetitive behavior symptoms correlated positively with exploration of object pictures and negatively with perseveration on social pictures. Results suggest that children with autism have a domain-general pattern of atypical visual attention that may represent an exaggeration of a typical attentional process and is related to a tendency to perseverate on images of interest and explore them in a more detail-oriented manner. Discrete measures of visual attention may therefore provide a reasonable means of quantifying aspects of the repetitive behavior phenotype in autism.