Structural neural phenotype of autism: preliminary evidence from a diffusion tensor imaging study using tract-based spatial statistics.

BACKGROUND AND PURPOSE: There is mounting evidence suggesting widespread aberrations in neural connectivity as the underlying neurobiology of autism. Using DTI to assess white matter abnormalities, this study implemented a voxelwise analysis and tract-labeling strategy to test for a structural neural phenotype in autism. MATERIALS AND METHODS: Subjects included 15 boys with autism and 8 controls, group-matched on age, cognitive functioning, sex, and handedness. DTI data were obtained by using a 3T scanner. FSL, including TBSS, was used to process and analyze DTI data where FA was chosen as the primary measure of fiber tract integrity. Affected voxels were labeled by using an integrated white matter tractography atlas. Post hoc correlation analyses were performed between FA of each affected fiber tract and scores on the Social Responsiveness Scale. RESULTS: The autism group exhibited bilateral reductions in FA involving numerous association, commissural, and projection tracts, with the most severely affected being the forceps minor. The most affected association tracts were the inferior fronto-occipital fasciculus and superior longitudinal fasciculus. There were no areas of increased FA in the autism group. All post hoc correlation analyses became nonsignificant after controlling for multiple comparisons. CONCLUSIONS: This study provides preliminary evidence of reduced FA along many long-range fiber tracts in autism, suggesting aberrant long-range corticocortical connectivity. Although the spatial distribution of these findings suggests widespread abnormalities, there are major differences in the degree to which different tracts are affected, suggesting a more specific neural phenotype in autism.

Speech and prosody characteristics of adolescents and adults with high-functioning autism and Asperger syndrome.

Speech and prosody-voice profiles for 15 male speakers with High-Functioning Autism (HFA) and 15 male speakers with Asperger syndrome (AS) were compared to one another and to profiles for 53 typically developing male speakers in the same 10- to 50-years age range. Compared to the typically developing speakers, significantly more participants in both the HFA and AS groups had residual articulation distortion errors, uncodable utterances due to discourse constraints, and utterances coded as inappropriate in the domains of phrasing, stress, and resonance. Speakers with AS were significantly more voluble than speakers with HFA, but otherwise there were few statistically significant differences between the two groups of speakers with pervasive developmental disorders. Discussion focuses on perceptual-motor and social sources of differences in the prosody-voice findings for individuals with Pervasive Developmental Disorders as compared with findings for typical speakers, including comment on the grammatical, pragmatic, and affective aspects of prosody.

Pharmacological interventions in autism: theoretical and practical issues.

Focused on issues of drug treatment in relation to autism. Pharmacological treatment studies in autism are complicated by various factors including a tremendous range of syndrome expression, a lack of robust animal models of the disorder, and various methodological problems. Theories have tended to follow treatments, and various neurochemical systems have been the focus of study. Neurochemical systems potentially implicated include those involving dopamine, norepinephrine, serotonin, and neuropeptides. The dopaminergic system has been the most extensively studied. Treatments developed are effective relative to certain disabling symptoms but "core" problems (e.g., in social relatedness and communication) appear less responsive to medications. The development of new approaches to assessment, including integration of behavioral and pharmacological approaches, is an important research priority.

Language regression in childhood.

Language regression is observed both in autistic regression and as part of acquired epileptic aphasia (Landau-Kleffner Syndrome). We prospectively identified 177 children with language regression at four major medical centers, and their clinical characteristics were recorded. Their mean age at regression was 22.8 months. The mean time-to-specialist referral was 38 months of age. Most children (88%) met criteria for autism or manifested autistic features. Males (P = 0.02) and children less than 3 years of age who regressed (P = 0.016) had a higher probability of developing autistic behaviors. Seizures were more common in children who regressed after they reached 3 years of age (P < 0.001), and children with seizures were less likely to have associated autistic regression (P < 0.001). Electroencephalogram abnormalities were reported in 37% of patients and were more common in children with seizures (P < 0.001). At last follow-up, language function was impaired in 88% of the children, although some improvement was noted in 57%. We conclude that the loss of previously acquired language at any age, even if that language only includes a few words or communicative gestures, is often associated with a more global regression in cognition and/or behavior and has serious implications for future function. Early identification and referral of these children is necessary to allow for diagnosis and intervention.

Toward a developmental operational definition of autism.

Traditional approaches to diagnosing autism emphasize delays in communication and socialization. Traditional diagnostic schemes typically list symptoms (e.g., lack of eye contact), but provide little guidance on how to incorporate information about developmental level in making a diagnosis. Because standardized measures of adaptive behavior can provide information about children's communication, socialization, and other behavior relative to their age, they may be useful tools for diagnosing autism. This study investigated the ability of the Vineland Adaptive Behavior Scales to identify children with autism. Vineland scores and measures of intellectual functioning were obtained for children with autism, PDDNOS, and other developmental disorders (DD). Discriminant function analyses indicated that the autism and combined nonautism (PDDNOS and DD) groups could be differentiated on the basis of socialization, daily living skills, and serious maladaptive behaviors. Socialization alone accounted for 48% of the variance in diagnosis. Using regression analyses derived from a large normative sample, adaptive behavior scores were predicted from chronological age (CA) and mental age (MA). Socialization scores in the autism group were substantially below the level predicted from CA or MA. An index derived from the ratio of actual to predicted socialization scores correctly classified 86% of both autism and nonautism cases. Findings suggest that comparison of obtained Vineland socialization scores to those predicted by CA or MA may be useful in clarifying the diagnosis of autism.

Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society.

Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.

Verbal bias in recognition of facial emotions in children with Asperger syndrome.

Thirteen children and adolescents with diagnoses of Asperger syndrome (AS) were matched with 13 nonautistic control children on chronological age and verbal IQ. They were tested on their ability to recognize simple facial emotions, as well as facial emotions paired with matching, mismatching, or irrelevant verbal labels. There were no differences between the groups at recognizing simple emotions but the Asperger group performed significantly worse than the control group at recognizing emotions when faces were paired with mismatching words (but not with matching or irrelevant words). The results suggest that there are qualitative differences from nonclinical populations in how children with AS process facial expressions. When presented with a more demanding affective processing task, individuals with AS showed a bias towards visual-verbal over visual-affective information (i.e., words over faces). Thus, children with AS may be utilizing compensatory strategies, such as verbal mediation, to process facial expressions of emotion.

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Season of birth in autism: a fiction revisited.

Variations of season of birth among autistic individuals were studied. The replicability of previously reported increases in birth rates in the months of March and August were examined in groups of individuals with autism or mental retardation (the comparison group). The sample was obtained from the Yale Child Study Center Developmental Disabilities Clinic and from the DSM-IV Autism/PDD field trial. Data were analyzed by applying the Jonckheere test of ordinal trend and the chi-square test, with Yates correction factor. With respect to March and August births, and with calculations based on the beginning and middle of the month, no significant seasonal effect was observed. Samples were subcategorized into verbal and mute groups, and again results failed to support the seasonality hypothesis.

Higher-functioning pervasive developmental disorders: rates and patterns of psychotropic drug use.

OBJECTIVE: To explore the frequency, characteristics, and associated target symptoms of psychotropic drug use among subjects with higher-functioning pervasive developmental disorders (HFPDDs). METHOD: A total of 109 children, adolescents, and adults (mean age = 13.9 years, SD = 6.9) consecutively seeking enrollment into the Yale Child Study Center's Project on Social Learning Disabilities were included in the study. Individuals in whom Asperger's disorder, autism, or pervasive developmental disorder-not otherwise specified had been previously diagnosed and who had a documented Full Scale IQ > or = 70 completed surveys on demographic, clinical, and medication history information. To naturalistically evaluate medication use patterns in this population, each drug class was analyzed with respect to demographic and clinical variables. RESULTS: In all, 55% of subjects were taking psychotropics, with 29.3% taking 2 or more medications simultaneously. Antidepressants were the most commonly used agents (32.1%), followed by stimulants (20.2%) and neuroleptics (16.5%). The clinical presentation of subjects taking psychotropic agents was heterogeneous, and most consistently included anxiety-related target symptoms (in 65% of medicated individuals). CONCLUSIONS: Psychotropic medication use appears to be common among subjects with HFPDDs, yet not generally based on the results of empirical research. Clinical heterogeneity among treated subjects suggests that psychiatric comorbidity may be overlooked in this population.

The screening and diagnosis of autistic spectrum disorders.

The Child Neurology Society and American Academy of Neurology recently proposed to formulate Practice Parameters for the Diagnosis and Evaluation of Autism for their memberships. This endeavor was expanded to include representatives from nine professional organizations and four parent organizations, with liaisons from the National Institutes of Health. This document was written by this multidisciplinary Consensus Panel after systematic analysis of over 2,500 relevant scientific articles in the literature. The Panel concluded that appropriate diagnosis of autism requires a dual-level approach: (a) routine developmental surveillance, and (b) diagnosis and evaluation of autism. Specific detailed recommendations for each level have been established in this document, which are intended to improve the rate of early suspicion and diagnosis of, and therefore early intervention for, autism.

A normed study of face recognition in autism and related disorders.

Although the interpretation of studies of face recognition in older children, adolescents, and adults with autism is complicated by the fact that participating samples and adopted methodologies vary significantly, there is nevertheless strong evidence indicating processing peculiarities even when task performance is not deficient. Much less is known about face recognition abilities in younger children with autism. This study employed a well-normed task of face recognition to measure this ability in 102 young children with autism, pervasive developmental disorder not otherwise specified (PDDNOS), and non-PDD disorders (mental retardation and language disorders) matched on chronological age and nonverbal mental age, and in a subsample of 51 children divided equally in the same three groups matched on chronological age and verbal mental age. There were pronounced deficits of face recognition in the autistic group relative to the other nonverbally matched and verbally matched groups. Performance on two comparison tasks did not reveal significant differences when verbal ability was adequately controlled. We concluded that young children with autism have face recognition deficits that cannot be attributed to overall cognitive abilities or task demands. In contrast to controls, there was a lower correlation between performance on face recognition and nonverbal intelligence, suggesting that in autism face recognition is less correlated with general cognitive capacity. Contrary to our expectation, children with PDDNOS did not show face recognition deficits.

Nosological and genetic aspects of Asperger syndrome.

The validity of Asperger syndrome (i.e., apart from high-functioning autism) continues to be the topic of considerable debate. Consistent with Asperger's original description of the condition there appear to be some important potential differences from autism if both conditions are strictly defined. Although the importance of genetic factors in the transmission of autism is increasingly clear it also appears that genetic factors may play an even more important role in Asperger syndrome (AS). The nosological validity of this condition and its relation to the various PDD spectrum disorder remains an important topic for future research. Well-designed and carefully controlled studies are needed in which patterns of comorbidity and associated problems in family members can be carefully assessed. Such studies will contribute to our understanding of the relationship of AS and autism and may clarify important genetic mechanisms of relevance to autism.

The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism.

Vineland Adaptive Behavior Scales Special Population norms are presented for four groups of individuals with autism: (a) mute children under 10 years of age; (b) children with at least some verbal skills under 10 years of age; (c) mute individuals who are 10 years of age or older; and (d) individuals with at least some verbal skills who are 10 years of age or older. The sample included 684 autistic individuals ascertained from cases referred for the DSM-IV autism/PDD field trial collaborative study and five university sites with expertise in autism. Young children had higher standard scores than older individuals across all Vineland domains. In the Communication domain, younger verbal children were least impaired, older mute individuals most impaired, and younger mute and older verbal individuals in the midrange. Verbal individuals achieved higher scores in Daily Living Skills than mute individuals. The expected profile of a relative weakness in Socialization and relative strength in Daily Living Skills was obtained with age-equivalent but not standard scores. Results high-light the importance of employing Vineland special population norms as well as national norms when evaluating individuals with autism.