Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic

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1 J Autism Dev Disord (2013) 43: DOI /s ORIGINAL PAPER Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic C. Ellie Wilson Nicola Gillan Deborah Spain Dene Robertson Gedeon Roberts Clodagh M. Murphy Stefanos Maltezos Janneke Zinkstok Katie Johnston Christina Dardani Chris Ohlsen P. Quinton Deeley Michael Craig Maria A. Mendez Francesca Happé Declan G. M. Murphy Published online: 16 March 2013 Ó Springer Science+Business Media New York 2013 Abstract An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56 % met DSM-5 ASD criteria. A further 19 % met DSM-5 (draft) criteria for Social Communication Disorder. Of those diagnosed with Autistic Disorder/Asperger Syndrome on DSM-IV-TR, 78 % met DSM-5 ASD criteria. Sensitivity of DSM-5 was significantly increased by reducing the number of criteria Francesca Happé and Professor Declan Murphy are joint senior authors. Data from this manuscript were presented at the International Meeting for Autism Research, Toronto, Canada, May Francesca Happé is part of the DSM-5 workgroup on neurodevelopmental disorders. C. E. Wilson (&) N. Gillan D. Spain G. Roberts C. M. Murphy S. Maltezos J. Zinkstok C. Dardani P. Q. Deeley M. Craig M. A. Mendez D. G. M. Murphy Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, King s College, London SE5 8AF, UK ellie.wilson@kcl.ac.uk C. E. Wilson N. Gillan D. Spain D. Robertson G. Roberts C. M. Murphy S. Maltezos J. Zinkstok K. Johnston C. Ohlsen P. Q. Deeley M. Craig M. A. Mendez D. G. M. Murphy Behavioural Genetics Clinic, Maudsley Hospital, South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK F. Happé Department of Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King s College, London SE5 8AF, UK required for a DSM-5 diagnosis, or by rating uncertain criteria as present, without sacrificing specificity. Reduced rates of ASD diagnosis may mean some ASD individuals will be unable to access clinical services. Keywords Autism Spectrum Disorder Diagnosis Prevalence DSM-5 Introduction Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a prevalence currently estimated at 1 in 80 individuals (Pinborough-Zimmerman et al. 2012). In recent years there has been a rise in reported rates of ASD. The reason for this is unclear, but changes in diagnostic practice are likely to have contributed (Fombonne 2005). Also, a formal diagnosis of an ASD is often used as a gatekeeper for services and support. Therefore changes in diagnostic practice may have important implications both for clinical prevalence rates and for an individual s care options. An Autism Spectrum Disorder is diagnosed on the basis of three domains: impaired social interaction, abnormal communication, and restricted and repetitive behaviours and interests. Using current diagnostic criteria in the International Classification of Diseases (ICD-10R; World Health Organization 1993) and the Diagnostic and Statistical Manual (DSM-IV-TR; American Psychiatric Association 2000), ASD comes under the umbrella term of Pervasive Developmental Disorder (PDD) and an individual may be defined as having one of four diagnostic subtypes according to the range of symptoms and the presence/ absence of factors such as developmental language delay and intellectual disability (i.e., Asperger Syndrome, Childhood Autism/Autistic Disorder, Atypical Autism,

2 2516 J Autism Dev Disord (2013) 43: PDD-unspecified). There are, however, problems with current diagnostic algorithms. First, distinguishing the social and communication domains is somewhat arbitrary since almost any example of communication is social and vice versa, and, several social and communication symptoms are covered by multiple criteria. For instance, behaviors indicative of poor socio-emotional reciprocity are currently covered in three criteria poor emotional reciprocity (social domain), lack of sharing enjoyment and interests (social domain), and poor reciprocal conversation (communication domain) (see Appendix 1). Second, there is a lack of evidence for significant differences between ASD diagnostic subtypes (once IQ matched) in etiology, neuropsychological profile, treatment or outcome, and poor clinical agreement when diagnosing (Ozonoff 2012). Unclear guidance on how to define people who have symptoms of ASD but do not meet full criteria also contributes to disagreement between clinicians. To address these problems, the Neurodevelopmental Disorders Workgroup, convened by the American Psychiatric Association (APA), has proposed a number of significant changes to the diagnostic criteria for ASD (Happé 2011; Swedo et al. 2012). The social and communication impairment criteria will be combined into a single set, thus reducing the current triad of impairments to two domains. In the social and communication domain there will be three criteria, instead of the current total of eight, and each criteria will include several examples of behaviors from across the lifespan that might indicate the presence of that symptom. Next, the previously distinct diagnostic subtypes will be collapsed into a single category of Autism Spectrum Disorder. People who do not present with the full range of symptoms will no longer be eligible for an ASD diagnosis, since there is no atypical or not otherwise specified category (as in ICD-10R, DSM-IV- TR). Instead, a new diagnostic category called Social Communication Disorder (SCD) has been proposed. This is defined as being outside the autism spectrum, but will provide diagnostic coverage for those individuals with symptoms in the social-communication domain, but who have never displayed repetitive, restricted behaviours or interests. The intention is that the changes to the diagnostic algorithm will reduce the wide variability between individuals on the autistic spectrum, by more clearly defining the symptoms required for diagnosis and by reducing the potential for clinicians to disagree. The effect of the proposed changes on diagnostic outcomes has been investigated in children and adolescents with several studies reporting that the specificity of the proposed DSM-5 criteria is good, but sensitivity is relatively poor, when judged against current ICD-10R or DSM-IV-TR criteria (Frazier et al. 2012; Matson et al. 2012; Mattila et al. 2011; McPartland et al. 2012; Taheri and Perry 2012; Worley and Matson 2012). This highlights a key concern of some: that the new criteria will fail to capture individuals currently receiving an ASD diagnosis who are on the broader spectrum according to DSM-IV-TR or ICD-10R criteria (e.g., Pervasive Developmental Disorder-not otherwise specified; PDD-NOS). As a consequence it is feared by some that these individuals will be denied access to services. Reassuringly, however, a large study of children diagnosed within the PDD category according to DSM-IV-TR suggested that sensitivity of DSM-5 is very good (0.91) although sensitivity in this study was much lower (0.53) (Huerta et al. 2012). The effect of the proposed changes for adults has received relatively little attention. This is of importance because ASD is a lifelong condition therefore most people with ASD are adults. Moreover, the number of individuals presenting for first diagnosis in adulthood is rapidly increasing: at the National ASD assessment service at the South London and Maudsley in the UK, the number of ASD assessments per month increased fourfold between 2005 and 2010 (Murphy et al. 2011). Further, diagnosis is particularly challenging in this group because a developmental history is often unavailable and/or unreliable; and presentation is frequently complicated by additional mental health conditions (Carpenter 2012). The only prior study that explored the agreement between current and proposed ASD criteria in adults included only individuals with (mostly profound) intellectual disability living in residential centers (Matson et al. 2012); they reported that approximately one third of the individuals who met DSM- IV-TR criteria no longer met them using the draft DSM-5. This study was a valuable first step. However, the majority of the ASD population does not have profound intellectual impairment (Baird et al. 2000) and such people are assessed within mental health or social/educational services. Also, it is unknown what proportion of individuals would qualify for the new, alternative diagnosis of SCD. Our primary aim, therefore, was to investigate how diagnostic outcomes of the DSM-5 algorithm differed from both ICD-10R and the DSM-IV-TR when applied in a clinical health service; and to compare all three algorithms to so-called gold-standard research diagnostic assessment tools (the Autism Diagnostic Interview-Revised (ADI-R; Lord et al. 1994) and Autism Diagnostic Observation Schedule (ADOS-G; Lord et al. 2000). Our secondary aims were to investigate whether diagnostic outcomes were affected by participant characteristics (age, sex, IQ, presence of additional mental health conditions), or alterations to the formulation of the proposed algorithm. Specifically, the impact of reducing the number of criteria required for a formal diagnosis was examined, and also the treatment of

3 J Autism Dev Disord (2013) 43: criteria where the clinician was uncertain or had insufficient information to code the item. when used in general population adult sample, (a =.90) (Lisspers et al. 1997). Method Participants Participants included 158 individuals consecutively assessed for ASD in a specialist National tertiary ASD diagnostic clinic for adults between January and May The clinic is situated within the South London and Maudsley NHS Foundation Trust. People are typically referred by their local family physician/general practitioner (GP) or consultant psychiatrist for a second opinion. In 8 cases diagnosis was inconclusive due to a history of acquired head injury or the presence of severe psychotic symptoms during assessment. Data from these cases were excluded from the study. The remaining 150 participants were aged years, with a mean age of 31 years. There were 110 males (mean age 32 years) and 40 females (mean age 31 years). Seventy-three patients already had a diagnosis of a mental health condition (most commonly depression, anxiety, Obsessive Compulsive Disorder (OCD), or Attention Deficit Hyperactivity Disorder (ADHD)), and only 7 of these had previously been diagnosed with ASD. Measures The ADI-R and ADOS-G are gold-standard research diagnostic assessment tools for ASD. The ADI-R is a semistructured interview with the parent or caregiver assessing ASD traits during childhood, and the ADOS-G is assessment completed with the patient assessing current traits of ASD. High levels of test retest reliability have been reported for both the ADI-R (in all domains, j [ 0.6; Hill et al. 2001), and the ADOS-G (in social and communication domains, j [ 0.7; Lord et al. 2000). Well-validated self-rating questionnaires were used to assess levels of other mental health conditions. The Obsessive Compulsive Inventory-Revised (OCI-R; Foa et al. 2002) was used to assess traits of OCD, and has high internal consistency when used among patients with OCD (a =.83) and patients with other anxiety disorders (a =.88), (Abramowitz and Deacon 2006). Symptoms of ADHD were assessed using the Barkley s Current and Childhood Symptom Scales (Barkley and Murphy 2005), which is a self- and informant-rated questionnaire used widely in clinical assessments for ADHD in adults (Barkley 2011). Finally, the Hospital Anxiety and Depression Scale (HADS; Zigmond and Snaith 1983) was used to assess levels of anxiety and depression, and has high levels of internal consistency Clinical Assessment Assessment included a detailed psychiatric assessment using ICD-10R research diagnostic criteria and, where possible (i.e., where parents were available, able and willing), an ADI-R. In the event that no parent was available for the ADI-R the person seeking diagnosis was asked to undergo the ADOS-G. In some cases both assessment tools were required to gather enough relevant information. Seventy-one individuals were assessed using the ADI-R, 62 were assessed with the ADOS-G, and 17 were assessed using both ADI-R and ADOS-G. All information obtained was compiled by the multidisciplinary clinical team a consultant psychiatrist, junior doctor, and ADI-R/ADOS-G administrator (nurse or psychologist) who together decided whether each criterion on the ICD-10R algorithm was fulfilled (see Appendix 1). If a patient met full ICD-10R criteria (a total of at least six symptoms must be present either currently or by history with at least two from the first domain and one from each of the second and third domains) and the symptoms were noted before the age of 3, they were diagnosed with Childhood Autism (if they exhibited a language delay) or Asperger Syndrome (if there was no evidence of a language delay). In line with ICD-10R guidelines, if a patient exhibited some autistic symptoms but did not meet full ICD-10R diagnostic criteria they were diagnosed with Pervasive Developmental Disorder, unspecified (PDDunspecified) or Atypical Autism. For the purposes of this study these two sub-threshold diagnostic groups were collapsed into a single PDD-unspecified group. In some cases it was not possible to decide confidently whether or not a symptom was present due to a lack of information, or because information obtained from patient and parent contradicted each other. In this event the criterion was coded as Unclear, and the team made the clinical diagnostic decision based on the gestalt of the information received. Of the 150 consecutive assessments, 113 were diagnosed with an ASD using ICD-10R criteria. Of these, 28 participants were subtyped as having Childhood Autism, 48 Asperger Syndrome, and 37 PDD-unspecified. Additional mental health conditions were also diagnosed in accordance with the ICD-10R (with the exception of adult ADHD which, in keeping with UK guidelines, was assessed using DSM-IV-TR), and the supplementary selfreport questionnaires were used to help inform assessment of OCD, ADHD, depression and anxiety (respectively, the OCI-R, Barkley s Current and Childhood Symptom Scales, and the HADS).

4 2518 J Autism Dev Disord (2013) 43: Where there was clinical suspicion that a participant might have intellectual disability (F70-73 in ICD-10R) or a significant lacuna in a neuropsychological function, they were referred for testing of general intellectual and executive functioning. These participants (N = 35) were tested using the Weschler Abbreviated Intelligence Scale-III, (WAIS III; Wechsler 1997) which revealed a mean Performance IQ of 87 (SD = 16, range ) and a mean Verbal IQ of 95 (SD = 18, range ). Mean full-scale IQ could not be calculated in 16 participants due to large discrepancies between Performance IQ and Verbal IQ; in the remaining 19 mean full-scale IQ was 90 (SD = 17, range ) and only 2 participants had an IQ below 70. The remaining 115 participants, not referred for such testing, were estimated to be in the normal range of general intellectual function based on educational attainment, employment, and informant report. Procedure For each participant the diagnostic outcome (ASD/not ASD; ICD-10R subtype of ASD; ADI-R and ADOS-G scores; presence of additional mental health problems) was reviewed by the research team. Information from the ICD-10R algorithm was used to determine whether each criterion on the proposed DSM-5 algorithm would be satisfied, and this was supplemented by anonymized reports from the ADI-R, ADOS-G, and the psychiatric interview. Appendix 2 shows how information in the ICD-10R maps onto the DSM-5. Each criterion could be coded as Yes, No, or Unclear. A participant was considered to meet criteria for ASD on the DSM-5 only when all three criteria in A and at least 2 out of 4 criteria in B were coded as Yes, as suggested in the criteria last posted by APA. If a participant did not meet criteria for ASD on the DSM-5 it was determined whether they would meet criteria for the alternative diagnosis of Social Communication Disorder (SCD). Re-coding was completed by pairs of researchers, and for 40 sets of participant data the re-coding was reviewed at consensus meetings with the whole team (10 researchers) to ensure agreement. Data were also re-coded to complete the DSM-IV-TR algorithm (demonstrated in Appendix 1), on which participants could be diagnosed as either ASD (Autistic Disorder/Asperger Syndrome) if they fulfilled at least six criteria, with at least 2 in domain A and 1 from each of domains B and C, or not ASD. Factors affecting agreement between ICD-10R, DSM- IV-TR and DSM-5 were also investigated. Participant characteristics (age, sex, IQ, additional mental health conditions) were compared between ASD positive and negative groups, and the effect of being assessed using the ADI-R, ADOS-G, or both, was also investigated. The effect of altering the DSM-5 algorithm was examined in two ways: by relaxing the number of criterion required for diagnosis, and by considering criteria that were coded as Unclear as either met or not met. To examine the effect of relaxing the number of criteria required for diagnosis the thresholds were reduced in Criteria A (from 3 to 2), or in Criteria B (from 2 to 1), or both. To examine the effect of including or excluding the Unclear items, the DSM-5 algorithm was re-coded by considering Unclear items to be present. This was relevant because the DSM-5 allows criteria to be met by history, and allowing or disallowing the Unclear criteria is likely to be crucial in many adult cases where multiple informants are not available. It was hypothesized that, (a) prevalence of Childhood Autism or Asperger Syndrome diagnosed using ICD-10R criteria would be similar to that using DSM-IV-TR and DSM-5, (b) most participants diagnosed with ASD on the ICD-10R but not the DSM-5 would be diagnosed with SCD, and (c) altering the DSM-5 algorithm would have significant effects on the rate of positive DSM-5 ASD diagnosis. Results Conclusions of Initial Diagnostic Assessments ICD-10R Versus DSM-5 (Table 1) Of the 150 participants, 113 (75 %) met criteria for an ASD according to the ICD-10R (Childhood Autism, Asperger Syndrome or PDD-unspecified). In contrast, however, according to the DSM-5, only 63 (42 %) met ASD criteria: this was a highly significant decline, v 2 (1) = 35.6, p \ A further 21 (14 %) participants met DSM-5 criteria for SCD. Overall, therefore, of those individuals positive for ASD on ICD-10R, 74 % (84 of 113) met criteria for ASD or SCD on DSM-5. Nevertheless, the proportion of individuals with no diagnosis at all (ASD or SCD) remained significantly higher when applying the DSM-5 criteria instead of ICD-10R (v 2 (1) = 62.5, p \ 0.001). None of the participants that were ASD negative using ICD-10R met diagnostic criteria for ASD (or SCD) according to the DSM-5, thus specificity of the DSM-5 was 100 %. DSM-IV-TR Versus DSM-5 (Table 1) The rate of ASD positive diagnosis using DSM-5 (42 %) was also significantly lower than the rate of Autistic Disorder or Asperger Syndrome assessed using DSM-IV-TR (53 %), v 2 (1) [ 82.5, p \ Additionally, two individuals were diagnosed with ASD on the DSM-5, but not with Autistic Disorder or Asperger Syndrome on the

5 J Autism Dev Disord (2013) 43: DSM-IV-TR, therefore specificity of the DSM-5 according to the DSM-IV-TR was Agreement with ADI-R and ADOS-G Results (Table 2) Agreement between diagnosis according to the ICD-10R/ DSM-IV-TR/DSM-5 and outcomes of the ADI-R and ADOS-G was calculated where this information was available. When measured against results of the ADI-R, the sensitivity of the ICD-10R and the DSM-IV-TR was higher than the DSM-5 (respectively 0.97, 0.97 and 0.79; both McNemar s p = 0.07), but their specificity was marginally Table 1 Outcome of initial assessment of 150 participants according to the ICD-10R, and outcome of data re-coded according to DSM-IV- TR and DSM-5: % (N) ICD-10R, % (N) DSM-IV-TR, % (N) DSM-5, % (N) Above/below ASD threshold Below ASD threshold Diagnosis of below ASD threshold participants ASD fullthreshold PDDunspecified or SCD No diagnosis 51 (76) 50 (74) 25 (37) 25 (37) 53 (80) 47 (70) N/A N/A 42 (63) 58 (87) 14 (21) 44 (66) lower. For the ADOS-G, sensitivity was also higher on the ICD-10R and the DSM-IV-TR than the DSM-5 (respectively 0.6, 0.7 and 0.5; McNemar s p = 0.07/0.01) and specificity was very similar. Factors Affecting Agreement Between ICD-10R and DSM-5 Participant Characteristics: Age, Gender, IQ, Diagnostic Subtype and Additional Mental Health Conditions Of the participants that were ASD positive using the ICD- 10R, there were no differences with respect to age, gender or IQ (where available) for those individuals that were ASD positive versus negative on the DSM-5. There was, however, a significant difference in rate of DSM-5 ASD positive diagnosis between ICD-10R subtypes, v 2 (2) = 31.58, p \ Significantly more participants diagnosed with ICD-10R Childhood Autism or Asperger Syndrome met DSM-5 criteria for ASD than those in the PDD-unspecified group (Table 3, Column A). The difference between ICD-10R defined Childhood Autism and Asperger Syndrome was not significant, v 2 (1) = 1.64, p = 0.2. With respect to additional mental health conditions, a significant difference was only found for OCD: higher rates of OCD were found in the group that were ASD positive on the DSM-5 than those that were ASD positive only on the ICD-10R, v 2 (1) = 4.58, p = 0.03 (Fig. 1). Table 2 Percentage of participants in each diagnostic group scoring above and below threshold on ADI-R and ADOS-G, and sensitivity and specificity of each diagnostic algorithm compared to ADI-R/ADOS-G. % (N) ADI-R below cut-off (%) a ADI-R above cut-off (%) a ADOS-G below cut-off (%) b ADOS-G above cut-off (%) b ICD-10R: Below ASD threshold (not ASD/PDD unspecified) ICD-10R: ASD (Asperger Syndrome/Childhood Autism) 96 (27) 4 (1) 75 (35) 25 (15) 36 (17) 64 (30) 32 (12) 68 (25) ICD-10R Sensitivity: 0.97* Sensitivity: 0.63* Specificity: 0.61 Specificity: 0.74 DSM-IV-TR: ASD negative 96 (27) 4 (1) 75 (36) 25 (12) DSM-IV-TR: ASD positive 36 (17) 64 (30) 28 (11) 71 (28) DSM-IV-TR Sensitivity: 0.97* Sensitivity: 0.70** Specificity: 0.61 Specificity: 0.77 DSM-5: ASD negative 83 (29) 17 (6) 64 (36) 36 (20) DSM-5: ASD positive 38 (15) 63 (25) 36 (11) 65 (20) DSM-5 Sensitivity: 0.81 Specificity: 0.66 * Difference between ICD-10R/DSM-IV-TR and DSM-5: McNemar s p \ 0.1 ** Difference between ICD-10R/DSM-IV-TR and DSM-5: McNemar s p \ 0.05 a ADI-R cut-off scores: Social = 10; Communication = 8; Repetitive behaviors/interests = 3 b DOS-G cut-off scores: Communication = 3; Social interaction = 6; Communication? Social = 10 Sensitivity: 0.50 Specificity: 0.77

6 2520 J Autism Dev Disord (2013) 43: Table 3 Percentage of participants that would be diagnosed with: (A) ASD on DSM-5; (B) Social Communication Disorder (SCD) on DSM-5; (C) ASD on DSM-5 if number of criterion required in Criteria A was reduced from 3 to 2, and/or the number of criterion required in Criteria B was reduced from 2 to 1 % (N) A B C ICD 10R/DSM-IV-TR diagnosis DSM-5 ASD DSM-5 SCD DSM-5 ASD: relax A DSM-5 ASD: relax B DSM-5 ASD: relax A and B ICD-10R, % (N) Not ASD, (N = 37) ASD, (N = 113) 56 (63) 19 (21) 69 (78)** 70 (79)** 87 (98)** Childhood autism, (N = 28) 82 (23) 11 (3) 86 (24) 93 (26) 96 (27) Asperger Syndrome, (N = 48) 69 (33) 15 (7) 83 (40)* 83 (40)* 98 (47)** PDD-unspecified, (N = 37) 19 (7) 30 (11) 38 (14)* 35 (13)* 65 (24)** DSM-IV-TR, % (N) Not ASD, (N = 70) 3 (2) 13 (9) 14 (10)* 10 (7)* 27 (19)** ASD, (N = 80) 77 (61) 15 (12) 85 (68)* 90 (72)** 99 (79)** * Difference between full criteria and relaxed threshold: McNemar s p \ 0.05 ** Difference between full criteria and relaxed threshold: McNemar s p \ for Criteria A or B, or both, were relaxed (all v 2 (1) [ 20.0, p s \.001). Of the 80 participants that were ASD positive on the DSM-IV-TR, sensitivity of the DSM-5 increased to 99 % when thresholds A and B were both relaxed, however specificity was significantly reduced. Uncertainty on the DSM-5 Algorithm: ASD Diagnostic Outcome When Criteria Coded as Unclear Were Considered to Be Present Fig. 1 Percentage of participants in ICD-10R/DSM-5 diagnostic groups that met criteria for additional mental health conditions. GAD General Anxiety Disorder, OCD Obsessive Compulsive Disorder, ADHD Attention Deficit Hyperactivity Disorder, None : No additional/alternative mental health condition. *p \ 0.05; **p \ 0.01 Finally, of the participants that were ASD positive using the ICD-10R, there was no significant effect of using different ASD assessment tools (ADI-R, ADOS-G, or both) on the outcome of the DSM-5, v 2 (2) = 4.20, p = Effects of Relaxing the DSM-5 Algorithm (Table 3, Column C) For the 113 participants that were ASD positive on the ICD-10R, the sensitivity of the DSM-5 increased significantly (and specificity remained at 100 %) when thresholds Of the participants diagnosed with ASD on the ICD-10R, 74 % received a diagnosis of ASD on the DSM-5 when criteria that were Unclear were treated as Yes ; this was a significant increase from 56 % when Unclear was coded as No (v 2 (1) = 51.46, p \.001). Specificity remained at 100 %. Discussion This is the first study to investigate how the DSM-5 criteria for ASD might perform in a specialist diagnostic clinic for adults without significant intellectual disability who form a large proportion of individuals with ASD. Our findings suggest that the specificity of the DSM-5 criteria, as compared to the currently used ICD-10R and DSM-IV-TR criteria, is good. However, sensitivity is relatively poor. For instance, 44 % of the participants that received a diagnosis of an ASD according to ICD-10R did not meet DSM-5 criteria. Similarly, 22 % of the individuals that met criteria for Asperger Syndrome or Autistic Disorder on DSM-IV-TR would not qualify for a DSM-5

7 J Autism Dev Disord (2013) 43: diagnosis of ASD. This is consistent with the only previous study that investigated agreement between current and proposed ASD criteria in intellectually disabled adults with ASD (Matson et al. 2012), and is cause for concern since these individuals, who have genuine difficulties and are most likely on the spectrum, may not be able to access services available to the ASD population if the DSM-5 is used to define eligibility (i.e., if it is used as an entry criteria ). The decline in sensitivity was highlighted when performance of each diagnostic algorithm was measured against results of gold-standard assessment tools. Both the ICD-10R and DSM-IV-TR had a 97 % chance of reporting a true ASD positive diagnosis according to the outcome of the ADI-R, and this fell to 81 % when using the DSM-5 a marginally significant decline. The chance of reporting a true negative, however, was slightly better when using the DSM-5 as compared to current diagnostic algorithms. Comparison with the ADOS-G revealed similar results, although there was a lower chance of true positives across all algorithms. It should be noted the ADI-R and ADOS-G were developed in order to align with the DSM- IV-TR, therefore the finding that the assessment tools fit better with current algorithms than with the DSM-5 is not entirely unexpected. Nevertheless, disagreement between diagnostic algorithms and gold-standard research assessment tools may lead to confusion in both research and clinical settings, therefore revisions of the assessment tools is likely to be required for use in adult populations. Given the evidence that a significant proportion of individuals currently considered to be on the autism spectrum may not be included in the DSM-5 ASD category, it is important to clarify what factors are associated with the likelihood that an individual will meet criteria. Encouragingly, there was no evidence of an effect of age or sex on diagnostic outcome, suggesting no particular demographic is more or less likely to receive an ASD diagnosis. We also found no effect of IQ in the subset of participants for which this information was available. This subset was a fairly small group, therefore conclusions are drawn with caution, however the results show no indication that higher-functioning people are more likely to be missed by the proposed DSM-5 criteria than lower functioning people a concern which has been raised in recent studies with children (McPartland et al. 2012). In the current study, the difference in rate of DSM-5 ASD positive diagnosis between the ICD-10R subtypes of Childhood Autism and Asperger Syndrome was non-significant. This suggests that adults with an Asperger Syndrome diagnosis will be at no greater risk of missing out on an ASD diagnosis when using DSM-5 than adults with Childhood Autism, and supports the DSM-5 proposal to combine these diagnoses into a single category. However, the third ICD-10R subtype PDD-unspecified had a significantly lower rate of ASD diagnosis using DSM-5 than both of the other two diagnostic subtypes. This is not necessarily cause for concern: people with a PDDunspecified diagnosis did not actually meet full diagnostic criteria on the ICD-10R either instead they showed significant ASD traits and were considered to be on the spectrum. What is perhaps of concern is that a quarter of people with an ICD-10R ASD diagnosis would not qualify for either ASD or SCD on the DSM-5, and the majority of those affected were of the PDD-unspecified subtype. This is the first study to report the proportion of people that would qualify for the new SCD diagnosis as currently drafted, but our results suggest this alternative category, which was intended to provide diagnostic coverage to many of those who will not qualify for the ASD diagnosis, may not solve the problem of the comparatively poor sensitivity of the DSM-5 relative to ICD-10R. The present data suggest that the sensitivity of the draft DSM-5 criteria, compared at least to ICD-10R and DSM- IV-TR, can be improved. Several authors have suggested that increased sensitivity without reduced specificity might be achieved by relaxing the proposed criteria (Frazier et al. 2012; Kapp and Ne eman 2012; McPartland et al. 2012). Our results supported this: it was found that relaxing thresholds in DSM-5 for social communication and social interaction (Criteria A), and/or repetitive patterns of behaviour, interests, and activities (Criteria B) allowed the inclusion of almost all people currently diagnosed with Childhood Autism or Asperger Syndrome, and the majority of those with PDD-unspecified while maintaining specificity. Therefore relaxing one, or both, criteria will likely allow the inclusion of more people currently considered to be ASD using ICD-10R and DSM-IV-TR, without weakening the boundaries between ASD and non-asd. In addition, clear guidance on how to deal with uncertainty in the DSM-5 classification system will be particularly important; the latest drafts of the DSM-5 criteria allow criteria to be met by history or current state, which may help where information is missing or uncertain. Rating criteria that were unclear as present versus absent had significant effects on the rates of DSM-5 ASD diagnosis. While this is the first study to examine the draft DSM-5 criteria in adults with ASD who do not have intellectual disabilities, some limitations should be noted. Like other studies comparing existing criteria to the DSM-5 draft, existing clinical notes and instruments that were used primarily for allocating current (ICD-10R) diagnostic categories were analyzed. It remains to be seen whether using the DSM-5 criteria in the clinic during assessment in a prospective fashion would result in different findings. For example, sensory sensitivities are not part of current clinical criteria and might be more thoroughly assessed in

8 2522 J Autism Dev Disord (2013) 43: future in clinics where DSM-5 criteria are adopted. Nonetheless one potentially useful feature of the present study, in contrast to many others, is the relatively large number of participants (25 %) who were assessed for ASD but found to be negative using current criteria. This allowed examination of specificity of the different diagnostic measures. Finally, it should be noted, of course, that it remains unclear whether existing ICD-10R or DSM- IV-TR criteria should be considered the gold-standard against which new criteria are compared; in the absence of biomarkers, the exact definition of ASD and its boundaries remain a matter for debate. Conclusions The specificity of the DSM-5 criteria, as compared to the currently used ICD-10R and DSM-IV-TR criteria is good but sensitivity is relatively low. This may be improved (without adversely affecting specificity) by relaxing DSM-5 criteria and by careful consideration of missing or uncertain symptom information. Acknowledgments Funding was provided by the Medical Research Council (MRC, UK), the EU Autism Imaging Study (AIMS) network (Grant Agreement: ), and the National Institute for Health Research Biomedical Research Centre for Mental Health at King s College London, Institute of Psychiatry and South London and Maudsley National Health Service Foundation Trust. The authors wish to thank all the participants involved in this study. Also the administrative support staff at the Behavioural Genetics Clinic: Frances Harwood, Pauline Domingo and Marie Simpson. Appendix 1 ICD-10R algorithm, with corresponding DSM-IV-TR items provided alongside each criterion. Of the participants that were diagnosed with ASD on the ICD-10R, the proportion of participants that were coded Yes, No and Unclear for each item is given. ICD-10R Algorithm (Corresponding DSM-IV item provided for each criterion). 1 Qualitative abnormalities in reciprocal social interaction are manifest in at least two of the following areas: a. Failure adequately to use eye-to-eye gaze, facial expression, body posture, and gesture to regulate social interaction DSM-IV-TR: 1a: Marked impairment in the use of multiple nonverbal behaviours such as eye-toeye gaze, facial expression, body postures, and gestures to regulate social interaction. ICD-10R: ASD positive group Yes No Unclear Appendix continued ICD-10R Algorithm (Corresponding DSM-IV item provided for each criterion). b. Failure to develop (in a manner appropriate to mental age, and despite ample opportunities) peer relationships that involve a mutual sharing of interests, activities, and emotions DSM-IV-TR: 1b: Failure to develop peer relationships appropriate to developmental level c. Lack of socio-emotional reciprocity as shown by an impaired or deviant response to other people s emotions; or lack of modulation of behaviour according to social context; or a weak integration of social, emotional, and communicative behaviours DSM-IV-TR: 1d: Lack of social or emotional reciprocity d. Lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g. a lack of showing, bringing, or pointing out to other people objects of interest to the individual). DSM-IV-TR: 1c: a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest) 2. Are there restricted, repetitive patterns of behavior, interests, and activities, as manifested by at least one of the following: a. A delay in, or total lack of, development of spoken language that is not accompanied by an attempt to compensate through the use of gesture or mime as an alternative mode of communication (often preceded by a lack of communicative babbling); DSM-IV-TR: 2a: delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime) b. Relative failure to initiate or sustain conversational interchange (at whatever level of language skills is present), in which there is reciprocal responsiveness to the communications of the other person DSM-IV-TR: 2b: in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others c. Stereotyped and repetitive use of language or idiosyncratic use of words or phrases DSM-IV-TR: 2c: stereotyped and repetitive use of language or idiosyncratic language d. lack of varied spontaneous make-believe or (when young) social imitative play DSM-IV-TR: 2d: lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level 3. Restricted, repetitive, and stereotyped patterns of behaviour, interests, and activities are manifest in at least one of the following areas: ICD-10R: ASD positive group Yes No Unclear Yes No Unclear

9 J Autism Dev Disord (2013) 43: Appendix continued Appendix continued ICD-10R Algorithm (Corresponding DSM-IV item provided for each criterion). ICD-10R: ASD positive group DSM-5 Algorithm ICD-10R:ASD positive group a. An encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal in content or focus; or one or more interests that are abnormal in their intensity and circumscribed nature though not in their content or focus DSM-IV-TR: 3a: encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus. b. Apparently compulsive adherence to specific, non-functional routines or rituals DSM-IV-TR: 3b: apparently inflexible adherence to specific, nonfunctional routines or rituals c. Stereotyped and repetitive motor mannerisms that involve either hand or finger flapping or twisting, or complex whole body movements DSM-IV-TR: 3c: stereotyped and repetitive motor mannerisms (e.g. hand or finger flapping or twisting, or complex whole-body movements) d. Preoccupations with part-objects or nonfunctional elements of play materials (such as their odor, the feel of their surface, or the noise or vibration that they generate). DSM-IV-TR: 3d: persistent preoccupation with parts of objects Appendix DSM-5 algorithm indicating the proportion of participants diagnosed with ASD on the ICD-10R that were coded Yes, No and Unclear for each item. Criteria from ICD-10R that contribute to each DSM-5 criterion are indicated, and underlined sections indicate sections not explicitly in ICD-10R criteria. Criteria from ICD-10R DSM-5 Algorithm CRITERION A: Are there persistent deficits in social communication and social interaction across contexts, not accounted for by general developmental delays, and manifest by ALL THREE of the following: ICD-10R: ASD positive group Yes No Unclear 2b; 1c; 1d 1. Deficits in socialemotional reciprocity; ranging from abnormal social approach and failure of normal back and forth conversation/ through reduced sharing of interests, emotions, and affect and response to total lack of initiation of social interaction? 1a; 2. Deficits in nonverbal communicative behaviors used for social interaction; ranging from poorly integrated- verbal and nonverbal communication, through abnormalities in eye contact and body-language, or deficits in understanding and use of nonverbal communication, to total lack of facial expression or gestures? 1b; 2d (but must be shared imaginative play) 3. Deficits in developing and maintaining relationships, appropriate to developmental level (beyond those with caregivers); ranging from difficulties adjusting behavior to suit different social contexts through difficulties in sharing imaginative play and in making friends to an apparent absence of interest in people? CRITERION B: Are there restricted, repetitive patterns of behavior, interests, and activities, as manifested by AT LEAST TWO of the following: 2c; 3c; 3d 1. Stereotyped or repetitive speech, motor movements, or use of objects (such as, simple motor stereotypies and echolalia, repetitive use of objects, or idiosyncratic phrases)? Yes No Unclear

10 2524 J Autism Dev Disord (2013) 43: Appendix continued DSM-5 Algorithm 2c; 3b 2. Excessive adherence to routines, ritualized patterns of verbal or nonverbal behavior, or excessive resistance to change (such as, motoric rituals, insistence on same route or food, repetitive questioning, or extreme distress at small changes)? 3a; 3d 3. Highly restricted, fixated interests that is abnormal in intensity or focus (such as, strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests)? 3d References 4. Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of environment (such as, apparent indifference to pain/heat/cold, adverse response to specific sounds or textures, excessive smelling or touching of objects, fascination with lights or spinning objects)? ICD-10R:ASD positive group Abramowitz, J. S., & Deacon, B. J. (2006). 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