Repetitive behaviors in autism spectrum disorders (ASD) range from motor stereotypy to immersion in restricted interests. The modified Children's Yale–Brown Obsessive Compulsive Scale for children with autism spectrum disorder (CYBOCS-ASD) includes a Symptom Checklist (behavior present or absent) and five severity scales (Time Spent, Interference, Distress, Resistance and Control).
We assembled CYBOCS-ASD data from 3 Research Units on Pediatric Psychopharmacology Autism Network trials to explore the component structure of repetitive behaviors in children with ASD. Raters trained to reliability conducted the CYBOCS-ASD in 272 medication-free subjects. Fifteen Checklist items were endorsed for less than 5% of the sample and were dropped. Principal Component Analysis (PCA) was used to explore the clustering of 23 checklist items. Component scores computed for each subject were correlated with other measures. We also examined the distribution of severity scales.
The subjects (229 boys, 43 girls; mean age = 7.8±2.6 years) met criteria for an ASD; half were intellectually disabled. The PCA resulted in a 5-component solution to classify repetitive behaviors (34.4% of the variance): Hoarding and Ritualistic Behavior; Sensory and Arranging Behavior; Sameness and Self-injurious Behavior; Stereotypy; Restricted Interests. Sensory and Arranging and Stereotypy components were associated with lower adaptive functioning (Pearson r ranged from .2 to .3; p < 0.003). The Resistance scale showed little variation with over 60% of sample with the highest score.
Rarely endorsed checklist items can be dropped. The Resistance item does not appear relevant for children with ASD.
autism spectrum disorder; clinical trials; outcome measures; repetitive behavior
This study identified subtypes of aggression in a sample of 206 children (174 boys, 32 girls) with autism spectrum disorder (ASD) who participated in two risperidone trials conducted by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. The classification of aggression subtypes was based on a review of brief narratives documented at baseline. The narratives were derived from a parent interview about the child’s two most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and non-aggressive. The aggression and SIB group had the highest proportion of children with IQ below 70. Children in the hot aggression group were slightly younger and had higher scores on the ABC-Irritability subscale than the non-aggression group. The SIB only group had the highest ABC-Irritability score. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend our understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD.
The primary goal of this study was to examine the impact of pregnancy, childbirth and menstruation on the onset of obsessive-compulsive disorder (OCD) and/or exacerbation of OCD symptoms.
One hundred twenty-six women attending a university-based OCD clinic aged 18-69 years who met DSM-IV criteria for OCD according to the Structured Clinical Interview for DSM-IV Disorders were interviewed retrospectively to assess OCD onset and symptom exacerbation in relationship to reproductive events. Women were placed into two groups: ever pregnant (Preg) and never pregnant (NPreg). The Preg group was further subdivided into those who reported onset of OCD in the perinatal period (perinatal-related, PR) and those that denied onset related to pregnancy (non-perinatal-related, NR). Between groups comparisons were done using a Student’s t-test for continuous measures and categorical variables were assessed using the chi-square test.
Of the 76 women in the Preg group, 32.1% (N = 25) had OCD onset in the perinatal period (PR group), 15.4% in pregnancy, 15.4% at postpartum, and 1.3% following miscarriage. Out of 132 total pregnancies, 34.1% involved an exacerbation of symptoms, 22.0% involved an improvement in OCD symptoms, and 43.9% did not change symptom severity in women with pre-existing illness. Women in the PR group and women with perinatal worsening of pre-existing OCD were more likely to have premenstrual worsening of OCD symptoms compared to NR women (65.5% vs. 39.3%, p = 0.047).
Findings from this study provide additional evidence that pregnancy and childbirth are frequently associated with the onset of OCD or worsening of symptoms in those with pre-existing disorder. In addition, there appears to be continuity between OCD onset and/or exacerbation across the reproductive life cycle, at least with menstruation and pregnancy.
This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.
Autism Spectrum Disorders; anxiety; measurement; comorbidity
A Structured Observational Analog Procedure (SOAP), an analogue measure of parent-child interactions, was used to assess treatment outcome in children with Autism Spectrum Disorder and serious behavior problems. It served as a secondary outcome measure in a 24-week, randomized trial of risperidone (MED; N=49) versus risperidone plus parent training (COMB; n=75) (ages 4–13 years). At 24-weeks, there was 28 % reduction in child inappropriate behavior during a Demand Condition (p=.0002) and 12 % increase in compliance to parental requests (p=.004) for the two treatment conditions combined. Parents displayed 64 % greater use of positive reinforcement (p=.001) and fewer repeated requests for compliance (p<.0001). In the analysis of covariance (ANCOVA), COMB parents used significantly more positive reinforcement (p=.01) and fewer restrictive statements (p<.05) than MED parents. The SOAP is sensitive to change in child and parent behavior as a function of risperidone alone and in combination with PMT and can serve as a valuable complement to parent and clinician-based measures.
Autism spectrum disorder; Autism; Observational measures; Behavioral interventions; Parent training; Clinical trials
A key area of concern in children with autism spectrum disorders (ASDs) are self-injurious behaviors (SIBs). These are behaviors that an individual engages in that may cause physical harm, such as head banging, or self-biting. SIBs are more common in children with ASD than those who are typically developing or have other neurodevelopmental disabilities. Therefore, it is important that clinicians who work with children with ASD have a solid understanding of SIB. The purpose of this paper is to review the research on the epidemiology of SIB in children with ASD, factors that predict the presence of SIB in this population, and the empirically supported behavioral treatments available.
self-injury; autism spectrum disorders; applied behavior analysis
Children with Pervasive Developmental Disorders (PDDs) have deficits in social interaction, delayed communication and repetitive behavior as well as impairments in adaptive functioning. Many children actually show decline in adaptive skills compared to age mates over time.
This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavior problems to medication alone (MED; N=49; risperidone 0.5 to 3.5 mg/day (if ineffective, switch to aripiprazole was permitted) or medication plus parent training (PT) (COMB; N=75). Parents of children in COMB received an average of 11.4 PT sessions. Standard scores and Age Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest.
Seventeen subjects did not have a post-randomization Vineland. Thus, we used a mixed model with outcome conditioned on the baseline Vineland scores. Both groups showed improvement over the 24-week trial on all Vineland domains. Compared to MED, Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group (p = 0.01 and 0.05; effect sizes = 0.35.and 0.22, respectively). On Age Equivalent scores, Socialization and Communication domains showed greater improvement in COMB versus MED (p=0.03, 0.05; effect sizes = 0.33 and 0.14 respectively). Using logistic regression, children in the COMB group were twice as likely to make at least 6 months gain (equal to the passage of time) in the Vineland Communication Age Equivalent score compared to MED (p = 0.02). After controlling for IQ, this difference was no longer significant.
Reduction of serious maladaptive behavior promotes improvement in adaptive behavior. Medication plus PT shows modest additional benefit over medication alone.
risperidone; parent training; Pervasive Developmental Disorders; children; adaptive behavior
The Research Units on Pediatric Psychopharmacology—Autism Network reported additional benefit when adding parent training (PT) to antipsychotic medication in children with autism spectrum disorders and serious behavior problems. The intent-to-treat analyses were rerun with putative predictors and moderators. The Home Situations Questionnaire (HSQ) and the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist were used as outcome measures. Candidate predictors and moderators included 21 demographics and baseline measures of behavior. Higher baseline HSQ scores predicted greater improvement on the HSQ regardless of treatment assignment, but no other predictors of outcome were observed. None of the variables measured in this study moderated response to PT. Antipsychotic medication plus PT appears to be equally effective for children with a wide range of demographic and behavioral characteristics.
Parent training; Pervasive developmental disorder; Autism; Risperidone; Predictor; Moderator
There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials.
To follow up on a 3-site 24-week randomized clinical trial (N=124) comparing antipsychotic medication alone (MED) to antipsychotic plus parent training (PT) in behavior management (COMB) for autism spectrum disorders with severe behavior problems. COMB had shown a significant advantage for child behavioral noncompliance (p=.006, d=.34), irritability (p=.01, d=.48), and hyperactivity/noncompliance (p=.04, d=.55), with a lower medication dose.
Method: A year after each participant’s termination we priority-mailed an assessment packet
with a return-addressed envelope; a phone call alerted the family. Failure to return packets within a month elicited recontact and offers to resend.
Eighty-seven of 124 families (70.2%) participated in follow-up. The improvement difference between treatments attenuated from post-treatment to follow-up for noncompliance (d=0.32 to d=0.12) and irritability (d=0.46 to d=0.03). Follow-up differences were nonsignificant. (The noncompliance difference was nonsignificant also at post-treatment for these 87.) 67% of COMB and 53% of MED were still taking risperidone, the original study medication. Most had needed dose adjustments or additional medication, and COMB no longer had a significantly lower dose. All COMB families but only 39% of MED reported seeking PT post-treatment. Daily living skills improvement during treatment predicted noncompliance improvement at follow-up for COMB, but noncompliance deterioration, and especially hyperactivity/noncompliance deterioration for MED-only children.
Study treatment experience/familiarity greatly influenced follow-up treatment: those who had received PT reported seeking it while those who had not experienced it tended not to seek it. The superiority of COMB over MED at post-treatment attenuated by over half at follow-up.
autism; antipsychotic; parent training; follow-up; clinical trial
Guanfacine has been shown to reduce hyperactive behaviors in children with attention-deficit/hyperactivity disorder (ADHD) and possibly in children with pervasive developmental disorder (PDD) and hyperactivity. The aim of this exploratory study was to examine whether gene variants encoding the multidrug resistance protein (MDR1 or ABCB1) , a drug transporter at the blood–brain barrier, are associated with variability in the efficacy of guanfacine in children with PDD and hyperactivity.
Children with PDD who participated in an 8-week open-label trial of guanfacine were genotyped for the C3435T single-nucleotide polymorphism (SNP) variant of the MDR1 gene, a variant reported to alter function of the transporter. The decrease from baseline to 8 weeks in parent-rated Aberrant Behavior Checklist (ABC) hyperactivity and Swanson, Nolan, and Pelham (SNAP) scores were analyzed by MDR1 genotype. Response was compared between subjects homozygous for the minor allele T of the C34535T MDR1 variant (T/T) versus other genotypes (C/T and C/C).
Disruptive behavior decreased during guanfacine treatment as assessed by several end points in the 25 enrolled children (23 boys and 2 girls). Genotype data were available from 22 children. Subjects with either C/T or C/C (n = 16) genotypes showed a three-fold greater improvement than T/T MDR1 C3435T genotype (n = 6) (mean decrease of 15.1 ± 12.6, or 50.7% from baseline, versus 4.5 ± 5.1, or 15.6% from baseline) in parent-rated ABC Hyperactivity scores over 8 weeks (p = 0.03). Parent-rated ADHD SNAP scores also differed by genotype (p = 0.05).
Gene variants in MDR1 may influence guanfacine response on hyperactive-impulsive behaviors via altered membrane transport. If replicated in larger samples, additional studies would be important to clarify the mechanisms underlying this effect and to determine its clinical significance.
Psychotropic medications, including the atypical antipsychotics, have historically been scrutinized for cardiac effects and risk of sudden death. Aripiprazole is an atypical antipsychotic approved for pediatric use in schizophrenia, bipolar I disorder, and autistic disorder. Adult studies have evaluated aripiprazole's effects on electrocardiograms, but no pediatric studies have been published to date.
Electrocardiographic data were collected from children and adolescents participating in a 14-week, prospective, open-label study (n=25) of aripiprazole for irritability in pervasive developmental disorder not otherwise specified and Asperger's disorder. A 12-lead electrocardiogram was obtained at the baseline and end point visits. The electrocardiograms were evaluated for abnormal findings, and the PR, QRS, QTc, and RR intervals were recorded. The QT interval was corrected using Bazett's, United States Food and Drug Administration (FDA) Pharmacology Division, and Fridericia's formulas.
Twenty-four subjects received both baseline and posttreatment electrocardiograms. The mean age was 8.6 years (range 5–17 years). The average final aripiprazole dose was 7.8 mg/day (range 2.5–15 mg/day). There were no significant differences noted with the PR, QRS, RR, and QTc intervals after aripiprazole therapy. Also, there was no significant correlation between the dose given and the percent change in the QTc. No post-treatment QTc exceeded 440 ms.
To our knowledge, this is the first systematic evaluation of the cardiac effects of aripiprazole in children and adolescents. The results are consistent with previously published literature in adults that aripiprazole has no significant cardiac effects and can be deemed a low risk for causing sudden death. It will be important to confirm these findings in a randomized controlled trial.
To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration–approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.
Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-γ (IFN-γ), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.
The neurobiology of autism spectrum disorders (ASDs) has become increasingly understood since the advent of magnetic resonance imaging (MRI). Initial observations of an above-average head circumference were supported by structural MRI studies that found evidence of increased total brain volume and early rapid brain overgrowth in affected individuals. Subsequent research revealed consistent abnormalities in cortical gray and white matter volume in ASDs. The structural integrity and orientation of white matter have been further elucidated via diffusion tensor imaging methods. The emergence of functional MRI techniques led to an enhanced understanding of the neural circuitry of ASDs, demonstrating areas of dysfunctional cortical activation and atypical cortical specialization. These studies have provided evidence of underconnectivity in distributed cortical networks integral to the core impairments associated with ASDs. Abnormalities in the default-mode network during the resting state have also been identified. Overall, structural and functional MRI research has generated important insights into the neurobiology of ASDs. Additional research is needed to further delineate the underlying brain basis of this constellation of disorders.
Autism; Autism spectrum disorder; Magnetic resonance imaging; Neurobiology; Review
This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed.
autism; autism spectrum disorder; autistic disorder; pervasive developmental disorder; treatment
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-011-1094-6) contains supplementary material, which is available to authorized users.
Importance of the Field
Autism spectrum disorders, or pervasive developmental disorders (PDDs), are neurodevelopmental disorders defined by qualitative impairment in social interaction, impaired communication, and stereotyped patterns of behavior. The most common forms of PDD are autstic disorder (autism), Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD NOS). Recent surveillance studies reveal an increase in the prevalence of autism and related PDDs. The use of pharmacologic agents in the treatment of these disorders can reduce the impact of interfering symptoms, providing relief for affected individuals and their families.
Areas Covered in this Review
This review examines results from neurobiologic research in an attempt to both elucidate the pathophysiology of autism and guide the development of pharmacologic agents for the treatment of associated symptoms. The safety and efficacy data of drugs currently in clinical use for the treatment of these symptoms, as well as pharmaceuticals currently under development, are discussed.
What the Reader will Gain
This comprehensive review will deepen the reader's current understanding of the research guiding the pharmacologic treatment of symptoms associated with autism and related PDDs. Areas of focus for future research are also discussed. The need for large-scale investigation of some commonly used pharmacologic agents, in addition to the development of drugs with improved efficacy and safety profiles, is made evident.
Take Home Message
Despite progress in the development of pharmacologic treatments for a number of interfering symptom domains associated with autism and other PDDs, a great deal of work remains.
aripiprazole; autism; autistic disorder; methylphenidate; PDDs; risperidone; treatment
Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder. While medication and psychotherapy advances have been very helpful to patients, many patients do not respond adequately to initial trials of serotonergic medication or cognitive-behavioral therapy (CBT) and require multiple treatment trials or combination therapies. Comorbidity may also influence treatment response. The role of streptococcal infections in pediatric OCD has become an area of intense scrutiny and controversy. In this article, current treatment methods for OCD will be reviewed, with special attention to strategies for treating OCD in children and in patients with comorbid tic disorders. Alternative psychotherapy strategies for patients who are highly anxious about starting CBT, such as cognitive therapy or augmentation with D-cycloserine, will be reviewed. Newer issues regarding use of antibiotics, neuroleptics, and glutamate modulators in OCD treatment will also be explored.
OCD; exposure/response prevention therapy; PANDAS; tic disorder
Aripiprazole was recently US FDA-approved to treat irritability in children and adolescents with autistic disorder aged 6–17 years. There are currently only two psychotropics approved by the FDA to treat irritability in the autistic population. This drug profile will discuss available studies of aripiprazole in individuals with pervasive developmental disorders, two of which led to its recent FDA approval. We will discuss the efficacy, as well as the safety and tolerability of the drug documented in these studies. In addition, the chemistry, pharmacokinetics, metabolism and mechanism of action of aripiprazole will be reviewed.
aripiprazole; Asperger’s disorder; autistic disorder; dehyro-aripiprazole; pervasive developmental disorder; pervasive developmental disorder not otherwise specified; quinolinone antipsychotic
Autism spectrum disorders (ASDs) are childhood onset developmental disorders characterized by social skills impairment, repetitive behavior, and for classic autistic disorder, a significant communication impairment. In addition to these core symptom domains, persons with ASDs frequently exhibit interfering behavioral symptoms, including irritability marked by aggression, self-injurious behavior (SIB), and severe tantrums. Aripiprazole is an atypical or newer generation antipsychotic with a unique mechanism of action impacting dopaminergic and serotonergic neurotransmission. The drug has been found efficacious for several indications, including most recently for use targeting irritability associated with autistic disorder in youth. Fragile X Syndrome (FXS) is the most common inherited cause of developmental disability and most common known single gene cause of ASDs. As in idiopathic ASDs, irritable behavior is often exhibited by persons with FXS. Research to date in this disorder, however, has not focused on this target symptom cluster. Initial pilot study has begun to assess the impact of aripiprazole on irritability in youth with FXS.
aripiprazole; autistic disorder; irritability; fragile X syndrome