References to Relevant Papers. ADOS Standardisation / Psychometrics. BeginningwithA

Transcription

1 References to Relevant Papers ADOS Standardisation / Psychometrics Bastiaansen, J. A., Meffert, H., Hein, S., Huizinga, P., Ketelaars, C., Pijnenborg, M., Bartels, A., Minderaa, R., Keysers, C. and De Bildt, A. (2011). Diagnosing autism spectrum disorders in adults: the use of Autism Diagnostic Observation Schedule (ADOS) module 4. J Autism Dev Disord, 41, Abstract: Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a reliable instrument with good predictive value. It can adequately discriminate ASD from psychopathy and typical development, but is less specific with respect to schizophrenia due to behavioral overlap between autistic and negative symptoms. However, these groups differ on some core items and explorative analyses indicate that a revision of the algorithm in line with Gotham et al. (J Autism Dev Disord 37: , 2007) could be beneficial for discriminating ASD from schizophrenia. Brian, J., Bryson, S. E., Garon, N., Roberts, W., Smith, I. M., Szatmari, P. and Zwaigenbaum, L. (2008). Clinical assessment of autism in high-risk 18-month-olds. Autism, 12, Abstract: Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non- ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fisher's exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD. De Bildt, A., Oosterling, I. J., Van Lang, N. D., Sytema, S., Minderaa, R. B., Van Engeland, H., Roos, S., Buitelaar, J. K., Van Der Gaag, R. J. and De Jonge, M. V. (2011). Standardized ADOS scores: measuring severity of autism spectrum disorders in a Dutch sample. J Autism Dev Disord, 41, Abstract: The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: , 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham's sample in age and level of verbal functioning. 1

2 Falkmer, T., Anderson, K., Falkmer, M. and Horlin, C. (2013). Diagnostic procedures in autism spectrum disorders: a systematic literature review. Eur Child Adolesc Psychiatry. At present, 'gold standard' diagnosis of autism spectrum disorders (ASD) is a lengthy and time consuming process that requires suitably qualified multi-disciplinary team (MDT) personnel to assess behavioural, historical, and parentreport information to determine a diagnosis. A number of different tools have been developed to assist in determination. To optimise the diagnostic procedures, the best diagnostic instruments need to be identified. This study is a systematic review addressing the accuracy, reliability, validity and utility of reported diagnostic tools and assessments. To be included in this review, studies must have (1) identified an ASD diagnostic tool; (2) investigated either diagnostic procedure or the tools or personnel required; (3) be presented in English; (4) be conducted in the Western world; (5) be one of three types of studies [adapted from Samtani et al. in Cochrane Database Syst Rev 3:1-13, 2011], viz. (a) cohort studies or cross-sectional studies, (b) randomised studies of test accuracy, (c) case-control studies. MEDLINE, PsychINFO, Scopus, EMBASE, and Cochrane Library databases were scrutinised for relevant literature published from 2000 inclusive on 20th January In total, 68 articles were included. 17 tools were assessed. However, many lacked an evidence base of high quality-independent studies. The Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) stood out with the largest evidence base and highest sensitivity and specificity. When the ADI-R and ADOS were used in combination they revealed levels of accuracy very similar to the correct classification rates for the current 'gold standard' diagnostic procedure viz % for ASD. There is scope for future studies on the use of the ADI-R and ADOS in combination. Gotham, K., A. Pickles, et al. (2009). "Standardizing ADOS scores for a measure of severity in autism spectrum disorders." J Autism Dev Disord, 39(5): The aim of this study is to standardize Autism Diagnostic Observation Schedule (ADOS) scores within a large sample to approximate an autism severity metric. Using a dataset of 1,415 individuals aged 2-16 years with autism spectrum disorders (ASD) or nonspectrum diagnoses, a subset of 1,807 assessments from 1,118 individuals with ASD were divided into narrow age and language cells. Within each cell, severity scores were based on percentiles of raw totals corresponding to each ADOS diagnostic classification. Calibrated severity scores had more uniform distributions across developmental groups and were less influenced by participant demographics than raw totals. This metric should be useful in comparing assessments across modules and time, and identifying trajectories of autism severity for clinical, genetic, and neurobiological research. Gotham, K., S. Risi, et al. (2008). "A replication of the Autism Diagnostic Observation Schedule (ADOS) revised algorithms." J Am Acad Child Adolesc Psychiatry, 47(6): OBJECTIVE: To replicate the factor structure and predictive validity of revised Autism Diagnostic Observation Schedule algorithms in an independent dataset (N = 1,282). METHOD: Algorithm revisions were replicated using data from children ages 18 months to 16 years collected at 11 North American sites participating in the Collaborative Programs for Excellence in Autism and the Studies to Advance Autism Research and Treatment. RESULTS: Sensitivities and specificities approximated or exceeded those of the old algorithms except for young children with phrase speech and a clinical diagnosis of pervasive developmental disorders not otherwise specified. CONCLUSIONS: Revised algorithms increase comparability between modules and improve the predictive validity of the Autism Diagnostic Observation Schedule for autism cases compared to the original algorithms. 2

3 Gotham, K., S. Risi, et al. (2007). "The Autism Diagnostic Observation Schedule: revised algorithms for improved diagnostic validity." J Autism Dev Disord, 37(4): Autism Diagnostic Observation Schedule (ADOS) Modules 1-3 item and domain total distributions were reviewed for 1,630 assessments of children aged 14 months to 16 years with an autism spectrum disorder (ASD) or with heterogeneous non-spectrum disorders. Children were divided by language level and age to yield more homogeneous cells. Items were chosen that best differentiated between diagnoses and were arranged into domains on the basis of multi-factor item-response analysis. Reflecting recent research, the revised algorithm now consists of two new domains, Social Affect and Restricted, Repetitive Behaviors (RRB), combined to one score to which thresholds are applied, resulting in generally improved predictive value. Gray, K. M., Tonge, B. J. and Sweeney, D. J Using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule with young children with developmental delay: evaluating diagnostic validity. J Autism Dev Disord, 38, Abstract: Few studies have focused on the validity of the ADI-R and ADOS in the assessment of preschool children with developmental delay. This study aimed to evaluate the diagnostic validity of the ADI-R and the ADOS in young children. Two-hundred and nine children aged months participated in the study, 120 of whom received a diagnosis of autism. ADI-R and ADOS diagnostic classifications were compared to consensus clinical diagnoses. Children with a clinical diagnosis of autism scored significantly higher on all algorithm domains of the ADI-R and ADOS. The ADOS performed better than the ADI-R in comparison to consensus clinical diagnosis. Characteristics of the ADI-R and ADOS false positive and false negative cases are explored. Further research is recommended in terms of examining which items of the ADI-R best predict a diagnosis of autism for very young children with developmental problems. Hus et al. (2011). The Adapted ADOS - Preliminary Findings Using a Modified Version of the ADOS for Adults Who Are Nonverbal or Have Limited Language Background: The Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000) is widely used in both research and clinical diagnostic evaluations. However, Module 4, the only module intended for adults, is limited to use with individuals who are verbally fluent. Modules 1 and 2, appropriate for individuals who are nonverbal or have limited language, have not been validated in adult samples. Because these instruments were intended for use with young children, many of the materials and activities were chosen to maximize opportunities for social interaction, such as requests and shared enjoyment, between the child and examiner. These activities and materials may not be interesting to and/or appropriate for use with adults. In addition, items used to score behavior in young children may not be of the same diagnostic utility in older individuals. Objectives: To adapt ADOS Modules 1 & 2 to be appropriate for use with adults who are nonverbal or have limited language. Methods: To create the Adapted ADOS, Module 1 and 2 activities and materials were modified to be more interesting and appropriate for adults. A pilot version of the Adapted ADOS was administered to 61 adults with ASD or non-spectrum diagnoses. Participants ranged from years of age. Protocol and algorithm items were chosen based on their ability to successfully discriminate ASD and non-asd groups. Total scores were generated from the algorithm items and Receiver Operating Curves (ROC; Siegel et al., 1989) were calculated to determine appropriate diagnostic cut-offs. Results: Modifications included changes to materials and activities. For example, Free Play toys were substituted with new, more adult-oriented materials (e.g., a real cell phone, a CD player) and some objects from the Module 3/4 Break. A 3

4 new Conversation activity was added to Module 2 to provide an additional opportunity to observe whether the presence of supporting materials facilitates the participant s ability to carry on a conversation with the examiner. Ninety-seven percent of adults with ASD and 100% of adults with non-spectrum diagnoses shifted attention to a target across the room in response to the examiner s shift in eye gaze or point. Given the high rate of response, the Response to Joint Attention activity was removed from the protocol. For adults receiving a Module 1, sensitivity of 83% and specificity of 75% was achieved. For adults receiving Module 2, sensitivity was 93% and specificity was 71%. Conclusions: The Adapted ADOS Modules 1 and 2 appear to be useful for the assessment of adults who are nonverbal or have limited language. Some behaviors that are diagnostically significant in young children (e.g., Response to Joint Attention) did not differentiate adults with and without ASD. These results are preliminary and the utility of the Adapted ADOS must be explored in larger samples. However, it is anticipated that these measures will facilitate future efforts to understand how ASD-related symptoms manifest across the lifespan. Kim, S. H. and Lord, C. (2012). Combining information from multiple sources for the diagnosis of autism spectrum disorders for toddlers and young preschoolers from 12 to 47 months of age. J Child Psychol Psychiatry, 53, Abstract: BACKGROUND: Purpose of this study was to systematically examine combined use of the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) for children under age 4 using newly developed and revised diagnostic algorithms. METHODS: Single and combined use of the ADI-R and ADOS algorithms were compared to clinical best estimate diagnoses for 435 children with autism spectrum disorders (ASD), 113 children with nonspectrum disorders, and 47 children with typical development from 12 to 47 months of age. Sequential strategies to reach a diagnostic decision by prioritizing administrations of instruments were also evaluated. RESULTS: Well-balanced sensitivities and specificities above 80% were obtained for ASD diagnoses using both instruments. Specificities significantly improved when both instruments were used compared to one. Scores that can be used to systematically prioritize administrations of instruments were identified. CONCLUSIONS: The ADI- R and ADOS make independent, additive contributions to more accurate diagnostic decisions for clinicians evaluating toddlers and young preschoolers with ASD. Sequential assessment strategies using the scores identified may be appropriate for some children. Le Couteur, A., Haden, G., Hammal, D. and Mcconachie, H Diagnosing autism spectrum disorders in pre-school children using two standardised assessment instruments: the ADI-R and the ADOS. J Autism Dev Disord, 38, Abstract: The reliable diagnosis of Autism/Autism Spectrum Disorder in pre-school children is important for access to early intervention and for accurate ascertainment for research. This paper explores the combined use of two standardised assessment instruments--the Autism Diagnostic Interview Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)--in a large sample of pre-school children. The children were recruited to research studies, and a 'best estimate' clinical diagnosis reached. The findings show good agreement between the instruments especially for children with core Autism. The instruments appear to have a complementary effect in aiding diagnosis and confirm the importance of a multidisciplinary assessment process with access to information from different sources and settings. The presence of repetitive behaviours during the ADOS appeared of diagnostic significance. Lord et al. (2013). Measuring Emerging Changes in Social Communication in Background: Clinical trials testing the effectiveness of medical treatments on the behaviors of children with ASD 4

5 have typically used parent questionnaires and clinician judgments heavily reliant on caregiver reports to measure outcomes. Using these measures, a number of approaches to decreasing behavior problems have been shown to be effective. Changes in response to behavioral clinical trials have typically been most evident for measures of general development and parent report measures of adaptive functioning. There has been much interest in measuring the effects of interventions on core features of autism. Several parent-report instruments have been proposed to fill these gaps. The advantage of observational measures, such as the ADOS, is that raters can remain truly blind to intervention status. However, though long-term changes in social-communication have been documented using calibrated scores from the Autism Diagnostic Observation Scale (ADOS), in general, the ADOS has not shown much effect of intervention. Other limitations include substantial correlations with verbal IQ; ADOS calibrated severity scores reduce these correlations, but result in children s scores being compared to other children of the same age and language level, which may underestimate the amount of change. Objectives: To design and test a standardized observational method of measuring change in core features of ASD that can be used by different research projects employing different contexts for these observations and that allows independent, blind scoring of change in response to behavioral interventions. Methods: The ADOS-C (ADOS-Change) provides a way of describing change in autism-specific social communication deficits. Standard 6 point codes for 15 social-communication behaviors are rated from a videotaped 10 minute interaction. Inter-rater and test-retest reliability have been established. Rather than contrasting scores of an individual child to normative scores from other children, the ADOS-C compares total scores of the same child in the same context at different times. Multiple raters are currently coding data for over 100 children between the ages of 18 months to 3 years at least three points: pre-intervention, post-intervention and follow-up from randomized controlled trials of three different early interventions and one multiple baseline study. These studies ranged greatly in length and intensity of treatment; all contexts were natural play during mother-child interactions. Results: For several, but not all interventions, preliminary analyses of the ADOS-C showed changes when the ADOS did not. Illustrative data will be presented. Clinical validity of the measure was also tested by comparing scores from children nominated by therapists and those reported by parents as showing the least and greatest amount of change in behavior. Factors associated with changes were complex and have implications for research designs and for use of observational methods documenting changes in social-communication behaviors. Conclusions: The potential to provide truly independent measures of more subtle changes in core features of ASD, as well as methodological issues for the ADOS-C and other measures of change in these features will be discussed, particularly in terms of planning and interpreting results of intervention studies. Lord, C., A. Pickles, et al. (1997). "Diagnosing autism: analyses of data from the Autism Diagnostic Interview." J Autism Dev Disord, 27(5): Results from ROC curves of items from two scales, the Autism Diagnostic Interview (ADI) and Autism Diagnostic Interview-Revised (ADI-R), operationalizing DSM-IV criteria for autism are presented for 319 autistic and 113 other subjects from 8 international autism centers. Analyses indicate that multiple items were necessary to attain adequate sensitivity and specificity if samples with varying levels of language were considered separately. Although considering only current behavior was generally sufficient when a combination cutoff and additive model was employed, predictive power was highest when history was taken into account. A single set of criteria, as operationalized by individually structured questions in the ADI/ADI-R, was effective in differentiating autism from mental handicap and language impairment in subjects with a range of chronological ages and developmental levels. Lord, C., S. Risi, et al. (2000). "The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism." J Autism Dev Disord, 30(3): The Autism Diagnostic Observation Schedule-Generic (ADOS-G) is a semistructured, standardized assessment of social interaction, communication, play, and imaginative use of materials for individuals suspected of having autism spectrum disorders. The observational schedule consists of four 30-minute modules, each designed to be administered to different individuals according to their level of expressive language. Psychometric data are 5

6 presented for 223 children and adults with Autistic Disorder (autism), Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) or nonspectrum diagnoses. Within each module, diagnostic groups were equivalent on expressive language level. Results indicate substantial interrater and test-retest reliability for individual items, excellent interrater reliability within domains and excellent internal consistency. Comparisons of means indicated consistent differentiation of autism and PDDNOS from nonspectrum individuals, with some, but less consistent, differentiation of autism from PDDNOS. A priori operationalization of DSM-IV/ICD-10 criteria, factor analyses, and ROC curves were used to generate diagnostic algorithms with thresholds set for autism and broader autism spectrum/pdd. Algorithm sensitivities and specificities for autism and PDDNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS. Lord, C., M. Rutter, et al. (1989). "Autism diagnostic observation schedule: a standardized observation of communicative and social behavior." J Autism Dev Disord, 19(2): The Autism Diagnostic Observation Schedule (ADOS), a standardized protocol for observation of social and communicative behavior associated with autism, is described. The instrument consists of a series of structured and semistructured presses for interaction, accompanied by coding of specific target behaviors associated with particular tasks and by general ratings of the quality of behaviors. Interrater reliability for five raters exceeded weighted kappas of.55 for each item and each pair of raters for matched samples of 15 to 40 autistic and nonautistic, mildly mentally handicapped children (M IQ = 59) between the ages of 6 and 18 years. Test-retest reliability was adequate. Further analyses compared these groups to two additional samples of autistic and nonautistic subjects with normal intelligence (M IQ = 95), matched for sex and chronological age. Analyses yielded clear diagnostic differences in general ratings of social behavior, specific aspects of communication, and restricted or stereotypic behaviors and interests. Clinical guidelines for the diagnosis of autism in the draft version of ICD-10 were operationalized in terms of abnormalities on specific ADOS items. An algorithm based on these items was shown to have high reliability and discriminant validity. Lord, C., M. Rutter, et al. (1994). "Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders." J Autism Dev Disord, 24(5): Describes the Autism Diagnostic Interview-Revised (ADI-R), a revision of the Autism Diagnostic Interview, a semistructured, investigator-based interview for caregivers of children and adults for whom autism or pervasive developmental disorders is a possible diagnosis. The revised interview has been reorganized, shortened, modified to be appropriate for children with mental ages from about 18 months into adulthood and linked to ICD-10 and DSM-IV criteria. Psychometric data are presented for a sample of preschool children. Luyster, R., K. Gotham, et al. (2009). "The Autism Diagnostic Observation Schedule-toddler module: a new module of a standardized diagnostic measure for autism spectrum disorders." J Autism Dev Disord, 39(9): The Autism Diagnostic Observation Schedule (ADOS; Lord et al., J Autism Dev Disord, 30(3): , 2000) is widely accepted as a "gold standard" diagnostic instrument, but it is of restricted utility with very young children. The purpose of the current project was to modify the ADOS for use in children under 30 months of age. A modified ADOS, the ADOS Toddler Module (or Module T), was used in 360 evaluations. Participants included 182 children with best estimate diagnoses of ASD, non-spectrum developmental delay or typical development. A final set of protocol and algorithm items was selected based on their ability to discriminate the diagnostic groups. The traditional 6

7 algorithm "cutoffs" approach yielded high sensitivity and specificity, and a new range of concern approach was proposed. Molloy, C. A., Murray, D. S., Akers, R., Mitchell, T. and Manning-Courtney, P. (2011). Use of the Autism Diagnostic Observation Schedule (ADOS) in a clinical setting. Autism, 15, Abstract: The aim of this study was to examine the Autism Diagnostic Observation Schedule (ADOS) as it is commonly used in clinical practice. ADOS classifications were compared to final diagnoses given by a multidisciplinary team to 584 children referred for evaluation for possible autism spectrum disorder (ASD) at the Cincinnati Children's Hospital Medical Center. A total of 177 children were evaluated with a Module 1 (87 No Words), 198 with a Module 2 (90 < 5 years) and 209 with a Module 3. Of these, 142 (26%) were diagnosed with autism, 185 (32%) with non-autism ASD, and 257 (44%) with non-spectrum disorders. Sensitivities were moderate to high on both original and revised algorithms, while specificities were substantially lower than those previously reported. This difference is likely attributable to the composition of the sample that included many children with a broad array of developmental and behavioral disorders. The clinical impression of the team member who administered the ADOS was critical to the accuracy of the overall diagnosis. Using numeric scores alone resulted in misclassification from false positive results. The study highlights the importance of the qualitative interactions of the ADOS activities as well as the score in diagnostic decision making. Oosterling, I., S. Roos, et al. (2010). "Improved diagnostic validity of the ADOS revised algorithms: a replication study in an independent sample." J Autism Dev Disord, 40(6): Recently, Gotham et al. (2007) proposed revised algorithms for the Autism Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim of the current study was to replicate predictive validity, factor structure, and correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms for Modules 1 and 2 in a large independent Dutch sample (N = 532). Results showed that the improvement of diagnostic validity was most apparent for autism, except in very young or low functioning children. Results for other autism spectrum disorders were less consistent. Overall, these findings support the use of the more homogeneous revised algorithms, with the use of similar items across developmental cells making it easier to compare ADOS scores within and between individuals. Risi, S., C. Lord, et al. (2006). "Combining information from multiple sources in the diagnosis of autism spectrum disorders." J Am Acad Child Adolesc Psychiatry, 45(9): BACKGROUND: Standard case criteria are proposed for combined use of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule to diagnose autism and to define the broader category of autism spectrum disorders. METHOD: Single and combined Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule algorithms were compared to best estimate diagnoses in four samples: U.S. (n = 960) and Canadian (n = 232) participants 3 years and older, U.S. participants younger than 36 months (n = 270), and U.S. participants older than 36 months with profound mental retardation (n = 67). RESULTS: Sensitivities and specificities of 80% and higher were obtained when strict criteria for an autism diagnosis using both instruments were applied in the U.S. samples, and 75% or greater in the Canadian sample. Single-instrument criteria resulted in significant loss of specificity. Specificity was poor in the sample with profound mental retardation. Lower sensitivity and specificity were also obtained when proposed criteria for broader spectrum disorders were applied. CONCLUSIONS: The Autism 7

8 Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule make independent, additive contributions to the judgment of clinicians that result in a more consistent and rigorous application of diagnostic criteria. Sappok, T., Diefenbacher, A., Budczies, J., Schade, C., Grubich, C., Bergmann, T., Bolte, S. & Dziobek, I. (2013). Diagnosing autism in a clinical sample of adults with intellectual disabilities: How useful are the ADOS and the ADI-R? Res Dev Disabil, 34, Abstract: Intellectual disability (ID) and autism spectrum disorder (ASD) are frequently co-occurring conditions. Carefully diagnosing ASD in individuals with ID would allow for more tailored clinical interventions that would improve mental health and quality of life. In this study, we evaluated the psychometric properties of the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) in a clinical sample of 79 adults with ID who were suspected of also having ASD. In the testable cases (68%), the ADOS was over-inclusive (specificity 45%) but highly sensitive (100%) of ASD. In the ADI-R, the feasibility was 37%, with a sensitivity of 88% and a specificity of 80%. Previously proposed adaptations of the ADOS algorithm were evaluated, and new items and tasks were suggested. The ADOS and the ADI-R were found to be valuable diagnostic tools for adults with ID. Adjustments of the setting and the tasks may further improve their feasibility and specificity. Aetiology Ring, A., Y. Barak, et al. (1997). "Evidence for an infectious etiology in autism." Pathophysiology, 4(2): Objective: Cyclical trends in birth rates that vary from general population patterns have been reported for several neuropsychiatric disorders. These data are used to test etiological hypotheses. Monthly and seasonal variations have been demonstrated for Autism possibly implicating an environmental pathogenic factor. We analyse data from Israel, focusing on viral epidemics. Method: Data covering a 30 year period ( ), including general population live births, autistic births, and incidence of viral encephalitis, viral meningitis, rubella, measles, and poliomyelitis were collected from Israel's Ministry of Health, Central Bureau of Statistics and National League for Autism. Periodicity and correlations between variables were analyzed. Results: Over the period studied, 290 autistic births were evaluated. Spectral analysis using the cosine function demonstrated a significant periodicity (tau) of 17.6 years (P=0.011) and near-significant periodicities of 3.2 years (P=0.07) and 4.1 years (P=0.27). Superposition of these three periods showed a highly significant fit to the annual autistic birth pattern (r=0.749, P=0.042). Multiple regression analysis of variables (encephalitis, meningitis, rubella, measles and poliomyelitis), yielded two significant findings: (a) during the period the incidence of measles correlated with the rhythmicity of Autistic births (r=0.49, P=0.036); (b) during the entire study period the incidence of viral meningitis correlated with this rhythmicity (r=0.37, P=0.042). It is note worthy that the only risk factor demonstrating a cyclical trend was viral meningitis (tau=3.0 years, P=0.032). Conclusions: Cyclical trends are significant in Autistic births in Israel. Autistic birth patterns are partially explained by the rates of measles and viral meningitis in the general population. There is a statistically significant environmental association between autism and both viral meningitis and measles that should be further investigated. 8

9 Attachment Croft, C., C. Beckett, et al. (2007). "Early adolescent outcomes of institutionally-deprived and non-deprived adoptees. II: language as a protective factor and a vulnerable outcome." J Child Psychol Psychiatry, 48(1): BACKGROUND: There is uncertainty about the extent to which language skills are part of general intelligence and even more uncertainty on whether deprivation has differential effects on language and non-language skills. METHODS: Language and cognitive outcomes at 6 and 11 years of age were compared between a sample of 132 institution-reared Romanian children adopted into UK families under the age of 42 months, and a sample of 49 children adopted within the UK under the age of 6 months who had not experienced either institutional rearing or profound deprivation. RESULTS: The effects of institutional deprivation were basically similar for language and cognitive outcomes at age 6; in both there were few negative effects of deprivation if it ended before the age of 6 months and there was no linear association with duration of deprivation within the 6 to 42 month range. For the children over 18 months on arrival (range months), the presence of even very minimal language skills (imitation of speech sounds) at the time of arrival was a strong beneficial prognostic factor for language and cognitive outcomes, but not for social/emotional/behavioural outcomes. Individual variations in adoptive parent characteristics were unrelated to differences in language or cognitive outcomes, possibly as a consequence of the limited variability in the adoptive family group. CONCLUSIONS: Minimal language probably indexes some form of cognitive reserve that, in turn, indexes the degree of institutional deprivation. Moran, H. (2010). Clinical observations of the differences between children on the autism spectrum and those with attachment problems: the Coventry Grid. Good Autism Practice, 26/10/2010 It is often problematic when a child has experienced a very difficult early life or serious abuse or trauma to determine whether the child has attachment problems or is on the autism spectrum or both, as the presenting problems may appear very similar on referral. Heather Moran is a Consultant Child Clinical Psychologist who works within a Child and Adolescent Mental Health Service (CAMHS). Over the last few years, she has met with other professionals in the West Midlands to discuss the similarities and differences between children on the autism spectrum and children with attachment problems and their response to interventions. This paper is a work in progress and presents the thoughts and ideas generated to date. It is presented here as others also ponder the same questions and Heather would welcome readers views on this. Link not available (not on PubMed) Rutgers, A. H., M. J. Bakermans-Kranenburg, et al. (2004). "Autism and attachment: a meta-analytic review." J Child Psychol Psychiatry, 45(6): METHOD: Sixteen studies on attachment in children with autism were reviewed, and ten studies with data on observed attachment security (N = 287) were included in a quantitative meta-analysis. RESULTS: Despite the impairments of children with autism in reciprocal social interaction, the majority of the studies found evidence for attachment behaviours in these children. In four samples using the Strange Situation procedure the average percentage of secure attachments amounted to 53% (n = 72). Meta-analytic results showed that children with autism were significantly less securely attached to their parents than comparison children, and the combined effect size for this difference was moderate (r =.24). Children with autism displayed less attachment security than comparisons without autism, but this difference disappeared in samples with children with higher mental development, and in samples in which autism was mixed with less severe symptoms of autistic spectrum disorders. CONCLUSIONS: It is concluded that attachment security is compatible with autism, and can be assessed with Strange 9

10 Situation type of procedures. The co-morbidity of autism and mental retardation appears to be associated with attachment insecurity. Rutgers, A. H., M. H. Van Ijzendoorn, et al. (2007). "Autism and attachment: the Attachment Q-Sort." Autism, 11(2): Children with autism are able to show secure attachment behaviours to their parents/caregivers. Most studies on attachment in children with autism used a (modified) Strange Situation Procedure (SSP) to examine attachment security. An advantage of the Attachment Q-Sort (AQS) over the SSP is that it can be attuned to the secure-base behaviour of children from special populations. In this study experts in the field of autism (both clinicians and researchers: N = 59) defined an AQS criterion sort for children with autism and tested its content validity. Separate criterion sorts were defined for the social subtypes aloof and active-but-odd, but the two criterion sorts could be combined into one AQS criterion sort for children with autism. It is concluded that with minor amendments the original Attachment Q-Sort is applicable in observing the attachment behaviour of children with autism. Rutgers, A. H., M. H. van Ijzendoorn, et al. (2007). "Autism, Attachment and Parenting: A Comparison of Children with Autism Spectrum Disorder, Mental Retardation, Language Disorder, and Non-clinical Children." J Abnorm Child Psychol., 35(5) Children with Autism Spectrum Disorder (ASD) have severe and pervasive impairments in the development of social interaction, which may affect the attachment relationship with their parents and may have an impact on parenting. In the current investigation 89 families with young children (mean age 26.5 months) were involved, who were diagnosed as ASD, mentally retarded (MR), or language delayed (LD), or part of a non-clinical comparison group. Attachment security was observed with the Brief Attachment Screening Questionnaire, and several parental selfreport questionnaires assessed the parenting style, parental efficacy, parental experiences of daily hassles, social support, and psychological problems. Children with ASD were rated as less secure compared to the other clinical and normal comparison groups. Parents of non-clinical children reported higher levels of authoritative parenting than parents in the ASD group and in the total clinical group, and they also received less social support. Parents of children with ASD coped remarkably well with the challenges of raising a child with ASD. Rutter, M. (1998). "Developmental catch-up, and deficit, following adoption after severe global early privation. English and Romanian Adoptees (ERA) Study Team." J Child Psychol Psychiatry, 39(4): The extent of developmental deficit and catch-up following adoption after severe global early privation was examined at 4 years in a sample of 111 Romanian children who came to the U.K. before the age of 2 years, and compared with respect to their functioning at the same age to a sample of 52 U.K. adopted children placed before the age of 6 months. The measures at 4 years included height, head circumference, and general cognitive level (assessed on both the McCarthy and Denver Scales). The children from Romania were severely developmentally impaired at the time of U.K. entry, with about half below the third percentile on height, on weight, on head circumference, and on developmental quotient. Many were also in a poor physical state with recurrent intestinal and respiratory infections. The catch-up in both physical growth and cognitive level appeared nearly complete at 4 years for those children who came to the U.K. before the age of 6 months, despite the fact that their background prior to U.K. entry was similar to the children who came to the U.K. when older. The developmental catch-up was also impressive, but not complete, in those placed after 6 months of age. The mean McCarthy General Cognitive 10

11 Index was 92 compared with 109 for the within-u.k. adoptees. The strongest predictor of level of cognitive functioning at 4 years was the children's age at entry to the U.K. It was concluded that the remaining cognitive deficit was likely to be a consequence of gross early privation, with psychological privation probably more important than nutritional privation. A further follow-up at age 6 years will determine whether there is continuing recovery after 4 years. Rutter, M., L. Andersen-Wood, et al. (1999). "Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) Study Team." J Child Psychol Psychiatry, 40(4): Six per cent of child in a sample of 111 children who were adopted into U.K. families from Romania, and who were systematically assessed at the ages of 4 and 6 years, showed autistic-like patterns of behaviour. A further 6% showed milder (usually isolated) autistic features. Such autistic characteristics were not found in a similarly studied sample of 52 children adopted in the first 6 months of life within the U.K. The children from Romania with autistic patterns showed clinical features closely similar to "ordinary" autism at 4 years but they differed with respect to the improvement seen by age 6 years, to an equal sex ratio, and to a normal head circumference. The children from Romania with autistic features tended to differ from the other Romanian adoptees with respect to a greater degree of cognitive impairment and a longer duration of severe psychological privation. Rutter, M., E. Colvert, et al. (2007). "Early adolescent outcomes for institutionally-deprived and non-deprived adoptees. I: disinhibited attachment." J Child Psychol Psychiatry, 48(1): BACKGROUND: Disinhibited attachment is an important sequel of an institutional rearing, but questions remain regarding its measurement, its persistence, the specificity of the association with institutional rearing and on whether or not it constitutes a meaningful disorder. METHOD: Children initially reared in profoundly depriving institutions in Romania and subsequently adopted into UK families were compared with respect to findings at 11 years with children who had not experienced institutional deprivation and who had been adopted within the UK before the age of 6 months. Measures included parental reports, a Strange Situation procedure modified for use in the home and systematic standardised investigator ratings of the children's behaviour. RESULTS: Disinhibited attachment, as reported by parents, showed a high degree of persistence from 6 to 11, but also a reduction over time in its frequency. Investigator ratings validated the parental reports but suggested that much of the fall in rate of disinhibited attachment was a function of the parental measure being less developmentally appropriate at 11 than it had been at 6. Disinhibited attachment was strongly associated with institutional rearing but there was not a significant increase in relation to duration of institutional deprivation beyond the age of 6 months. Mild, but not marked, disinhibited attachment was quite frequent in non-institutionalised adopted children but both the course and correlates indicated that its meaning was probably quite different. In the institution-reared children, disinhibited attachment was associated with a marked increase in service usage and associations with other forms of psychopathology. CONCLUSIONS: Disinhibited attachment constitutes a valid, and handicapping, clinical pattern that is strongly associated with an institutional rearing. Rutter, M., J. Kreppner, et al. (2007). "Early adolescent outcomes of institutionally deprived and non-deprived adoptees. III. Quasi-autism." J Child Psychol Psychiatry, 48(12): BACKGROUND: Some young children reared in profoundly depriving institutions have been found to show autisticlike patterns, but the developmental significance of these features is unknown. METHODS: A randomly selected, age- 11

12 stratified, sample of 144 children who had experienced an institutional upbringing in Romania and who were adopted by UK families was studied at 4, 6, and 11 years, and compared with a non-institutionalised sample of 52 domestic adoptees. Twenty-eight children, all from Romanian institutions, for whom the possibility of quasi-autism had been raised, were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) at the age of 12 years. RESULTS: Sixteen children were found to have a quasi-autistic pattern; a rate of 9.2% in the Romanian institution-reared adoptees with an IQ of at least 50 as compared with 0% in the domestic adoptees. There were a further 12 children with some autistic-like features, but for whom the quasiautism designation was not confirmed. The follow-up of the children showed that a quarter of the children lost their autistic-like features by 11. Disinhibited attachment and poor peer relationships were also present in over half of the children with quasi-autism. CONCLUSIONS: The findings at age 11/12 years confirmed the reality and clinical significance of the quasi-autistic patterns seen in over 1 in 10 of the children who experienced profound institutional deprivation. Although there were important similarities with 'ordinary' autism, the dissimilarities suggest a different meaning. Autism Phenotype Kim, S. H. and C. Lord (2010). "Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedule (ADOS)." Autism Res 3(4): Restricted and repetitive behaviors (RRBs) observed during the Autism Diagnostic Observation Schedule [ADOS: Lord et al., 2000] were examined in a longitudinal data set of 455 toddlers and preschoolers (age 8-56 months) with clinical diagnosis of Autism Spectrum Disorders (ASD; autism, n=121 and pervasive developmental disorders-not otherwise specified (PDD-NOS), n=71), a nonspectrum disorder (NS; n=90), or typical development (TD; n=173). Even in the relatively brief semi-structured observations, GEE analyses of the severity and prevalence of RRBs differentiated children with ASD from those with NS and TD across all ages. RRB total scores on the ADOS were stable over time for children with ASD and NS; however, typically developing preschoolers showed lower RRB scores than typically developing toddlers. Nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children with PDD-NOS, NS, and TD than younger children under 2 years and those with autism. Item analyses revealed different relationships between individual items and NVIQ, age, diagnosis, and gender. These findings are discussed in terms of their implications for the etiology and treatment of RRBs as well as for the framework of ASD diagnostic criteria in future diagnostic systems. Klin, A., C. A. Saulnier, et al. (2007). "Social and communication abilities and disabilities in higher functioning individuals with autism spectrum disorders: the Vineland and the ADOS." J Autism Dev Disord 37(4): The relationship between adaptive functioning (ability) and autism symptomatology (disability) remains unclear, especially for higher functioning individuals with autism spectrum disorder (ASD). This study investigates ability and disability using the Vineland and Autism Diagnostic Observation Schedule (ADOS), respectively, in two clinical samples of children with ASD. Participants included 187 males with VIQ > 70. Vineland scores were substantially below VIQ, highlighting the magnitude of adaptive impairments despite cognitive potential. A weak relationship was found between ability and disability. Negative relationships were found between age and Vineland scores and no relationships were found between age and ADOS scores. Positive relationships were found between IQ and Vineland Communication. Results stress the need for longitudinal studies on ability and disability in ASD and emphasize the importance of adaptive skills intervention. 12

13 Lord, C., E. Petkova, et al. (2011). "A Multisite Study of the Clinical Diagnosis of Different Autism Spectrum Disorders." Arch Gen Psychiatry, DOI: /archgenpsychiatry CONTEXT: Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. OBJECTIVE: To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. DESIGN: Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. SETTING: Participants were recruited through 12 university-based autism service providers into a genetic study of autism. PARTICIPANTS: A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. Main Outcome Measure Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. RESULTS: Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. CONCLUSIONS: Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function. Richler, J., R. Luyster, et al. (2006). "Is There a 'Regressive Phenotype' of Autism Spectrum Disorder Associated with the Measles-Mumps-Rubella Vaccine? A CPEA Study." J Autism Dev Disord, 36(3): A multi-site study of 351 children with Autism Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews to describe the children's early acquisition and loss of social-communication milestones. For the majority of children with ASD who had experienced a regression, pre-loss development was clearly atypical. Children who had lost skills also showed slightly poorer outcomes in verbal IQ and social reciprocity, a later mean age of onset of autistic symptoms, and more gastrointestinal symptoms than children with ASD and no regression. There was no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination. The implications of these findings for the existence of a 'regressive phenotype' of ASD are discussed. Volkmar, F. R., A. Klin, et al. (1994). "Field trial for autistic disorder in DSM-IV." Am J Psychiatry, 151(9): OBJECTIVE: This project focused on the development of the definition of autism for DSM-IV. METHOD: Multiple sites were involved in obtaining information regarding 977 patients with the following clinician-assigned diagnoses: autism (N = 454), other pervasive developmental disorders (N = 240), and other disorders (N = 283). A standard coding system was used, and the raters (N = 125) had a range of experience in the diagnosis of autism. Patterns of agreement among existing diagnostic systems were examined, as was the rationale for inclusion of other disorders within the class of pervasive developmental disorders. RESULTS: The DSM-III-R definition of autism was found to be overly broad. The proposed ICD-10 definition most closely approximated the clinicians' diagnoses. Inclusion of other 13