Background
Autism spectrum disorders (ASDs) comprise a group of neuropsychiatric disorders that include autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS). They are distinguished from other psychiatric disorders by the presence of deficits in reciprocal social behavior, variously accompanied by deficits in communication, and/or repetitive or stereotyped behaviors. The DSM-III-R [
1] and DSM-IV [
2] have operationalized the required diagnostic criteria necessary for establishing diagnoses of ASDs based on the presence or absence of a set of categorical symptoms.
While a thorough evaluation by an expert clinician who has significant experience in specific diagnoses is considered the best method of diagnosing complex conditions such as ASDs, structured diagnostic interviews have been developed to help non-expert clinicians elicit the required information for these diagnoses. The most widely used structured interview tool for establishing a diagnosis of autism in the research setting is the Autism Diagnostic Interview-Revised (ADI-R). This interviewer requires specelized training in order to administer it, and the training to become proficient in its administration is expensive and time consuming. Additionally, the ADI-R takes at least 2 hours to complete making it of limited feasibility in clinical settings and in large population-based studies.
In contrast to the 93 questions and associated complex algorithms of the ADI-R, the DSM includes only 16 items in its diagnostic criteria for ASDs. Moreover, because the literature clearly indicates that most individuals with ASD have other comorbid conditions such as Attention-Defecit/Hyperactivity Disorder (ADHD) and mood disorders [
3‐
7] and the ADI-R by itself does not assess other disorders that are pervasive in this population, another means for diagnosing other conditions is necessary and increases the length of time needed for a full assessment. This situation calls for the development of simplified instruments to aid in the assessment of ASDs in clinical and non-clinical settings.
Several attempts have been made to simplify the complexity of the assessment process for youth with ASDs. One such effort is development of the Social Responsiveness Scale (SRS), a paper and pencil instrument that can be completed by parents or teachers in 15-20 minutes. Constantino and colleagues [
8,
12] demonstrated its concurrent and discriminant validity as a measure of ASDs. As part of these efforts, Constantino et al. [
8] compared the SRS with the ADI-R in 61 child psychiatric patients. Correlations between SRS scores and ADI-R algorithm scores for DSM-IV criterion sets were on the order of 0.7. SRS scores were unrelated to I.Q. and exhibited inter-rater reliability on the order of 0.8. Though SRS is a valid quantitative measure of autistic traits, the instrument lacks the ability to distinguish autism from the spectrum (Asperger's disorder and PDD-NOS) in individuals with ASD [
8]. Despite the utility of the SRS as a screening tool for ASD, there continues to be a need to have a simplified DSM-based structured diagnostic interview module to aid in the diagnosis of individuals with ASD in clinical and research settings.
The main aim of the present study was to evaluate the concurrent and discriminant validity of a simplified, relatively brief, structured, diagnostic interview closely linked to the defining features of ASDs in the DSM (see Table
1). To examine the concurrent validity of this instrument, we examined its correspondence with a gold standard expert clinician's diagnoses in a large sample of clinically referred youth with ASDs. In addition, we examined its correspondence with the SRS because of the previously documented excellent correspondence between the SRS and the ADI-R [
8]. To examine the discriminant validity of the DSM-ASD structured diagnostic interview, we calculated its specificity comparing subjects with ASD with those from a large sample of clinic referred youth with ADHD. We hypothesized that our DSM-based structured diagnostic interview for ASDs would have good concurrent and discriminant validity.
Table 1
ASD symptoms for the structured interview, DSM-III-R and DSM-IV
A. THESE ARE SOME QUESTIONS ABOUT HOW YOUR SON/DAUGHTER RELATES TO OTHERS. | A. QUALITATIVE IMPAIRMENT IN RECIPROCAL SOCIAL INTERACTION
|
(1).
QUALITATIVE IMPAIRMENT IN SOCIAL INTERACTION
|
1. Did s/he seem unusually unaware of the existence or feelings of others? | 1. Marked lack of awareness of the existence of or feelings of others |
(d) Lack of social or emotional reciprocity
|
2. Did s/he not come for comfort even when hurt, or did s/he seek comfort in an odd way | 2. No or abnormal seeking of comfort at times of distress | |
3. Was s/he unable to imitate others when appropriate? | 3. No or impaired imitation | |
4. Does s/he have difficulty playing cooperatively with other children? | 4. No or abnormal social play |
(c) A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people
|
5. Is s/he uninterested in making peer friendships? Or if s/he is interested, does s/he seem to understand the conventions of social interaction? | 5. Gross impairment in ability to make peer friendships |
(b) Failure to develop peer relationships appropriate to developmental level
|
B. THESE ARE SOME QUESTIONS ABOUT HOW YOUR SON/DAUGHTER COMMUNICATES OR PLAYS WITH OTHERS.
| B. QUALITATIVE IMPAIRMENT IN VERBAL AND NONVERBAL COMMUNICATION, AND IN IMAGINATIVE ACTIVITY
| (2). QUALITATIVE IMPAIRMENTS IN COMMUNICATION
|
1. Is s/he unable to communicate? | 1. No mode of communication, such as communicative babbling, facial expression, gesture, mime, or spoken language | (a) 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) |
2. Does s/he avoid looking at people or avoid greeting people? If no, ask: Does s/he ignore people around her/him, dislike being held? | 2. Markedly abnormal nonverbal communication, as in the use of eye-to-eye gaze, facial expression, body posture, or gestures to initiate or modulate social interaction |
(1) (a) Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction
|
3. Is s/he uninterested in imaginative activities or stories? | 3. Absence of imaginative activity, such as playacting of adult roles, fantasy characters, or animals; lack of interest in stories about imaginary events | (d) Lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level |
4. When s/he speaks does her/his tone seem odd? | 4, Marked abnormalities in the production of speech, including volume, pitch, stress, rate, rhythm, and intonation | |
5. Did s/he repeat words or phrases s/he has just heard, in place of responding to what was said? Did s/he often use the wrong pronouns to refer to her/himself or others, or refer to him/herself in the third person, as "he wants a remarks cracker?" | 5. Marked abnormalities in the form or content of speech, including stereotyped and repetitive use of speech; use of "you" when "I" is meant; idiosyncratic use of words or phrases; or frequent irrelevant remarks | (c) Stereotyped and repetitive use of language or idiosyncratic language |
6. Did s/he seldom, if ever, start a conversation with someone else, even if s/he might talk to her/himself? | 6. Marked impairment in the ability to initiate or sustain a conversation with others, despite adequate speech | (b) In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others |
C. THESE ARE QUESTIONS ABOUT SON/DAUGHTER' S ACTIVITIES OR INTERESTS
| C. MARKEDLY RESTRICTED REPERTOIRE OF ACTIVITIES AND INTERESTS
|
(3) R
ESTRICTED REPETITIVE AND STEREOTYPED PATTERNS OF BEHAVIOR, INTERESTS, AND ACTIVITIES
|
1. Did s/he ever have any repetitive patterns of behavior such as hand movements, clapping or twirling? | 1. Stereotyped body movements, e.g., hand-flicking or -twisting, spinning, head-banging, complex whole-body movements |
(c) Stereotyped and repetitive motor mannerisms
|
2. Did s/he ever have any prolonged attachments to certain objects, either holding them or staring at them, or lining them up in a repetitive pattern? | 2. Persistent preoccupation with parts of objects or attachment to unusual objects |
(d) Persistent preoccupation with parts of objects
|
3. Did s/he ever get unusually upset if there were even small changes in where things were placed in the house? | 3. Marked distress over changes in trivial aspects of environment | |
4. Or get upset when there are changes in daily routine? | 4. Unreasonable insistence on following routines in precise detail |
(b) Apparently inflexible adherence to specific, nonfunctional routines or rituals
|
5. Does s/he have an extremely restricted range of interests, or a preoccupation with one very narrow interest | 5. Markedly restricted range of interests and a preoccupation with one narrow interest |
(a) Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus
|
Discussion
The main purpose of the present study has been to evaluate the concurrent and discriminant validity of a simplified DSM-based structured diagnostic interview for the assessment of ASDs in a clinical setting. The present study reports excellent agreement of the DSM-based ASD structured diagnostic instrument with a gold standard expert clinician diagnosis of ASD based on a DSM-IV clinical assessment through detailed interviews with the patient and the parent. Results also showed excellent sensitivity and specificity when comparisons were made between subjects with ASD and subjects with ADHD. These results indicate that our DSM-based structured diagnostic interview for ASD can be a useful and cost-effective standardized assessment instrument for reliably identifying ASD in clinical and research settings. Many clinics and research settings employ diagnostic structured interviews for screening a broad range of psychiatric disorders but these structured interviews lack measures to evaluate ASD. Therefore, this DSM based structured diagnostic interview - that is administered in a similar manner as structured interviews - would complement methods that are often used and can be easily added to the diagnostic interviews. This may improve the efficiency of the assessment, as it is included with screening of other psychiatric conditions.
Our design provides a reasonable estimate of sensitivity (i.e., the probability of our structured interview correctly identifying ASD cases). Remarkably, the sensitivity of the structured interview was extremely high, 94%. Equally remarkable is the finding of a 95% sensitivity of an SRS t-score of 60 or higher (accepted cut-off for a screen of ASD) as an indicator of the gold standard diagnosis. Consistent with these findings, 97% of subjects with our DSM based structured interview diagnosis of ASD also had an SRS t-score in the clinical range (≥ 60). If replicated, these findings would support the utility of a simple to use structured diagnostic instrument based on the defining items for ASD in the DSM-IV to help identify youth with ASD.
Results from our analysis show that the correspondence between our DSM-based structured interview for ASD with the expert clinician assessment was unrelated to the IQ of the subjects in both clinical samples. In addition, our structured interview allowed for the diagnosis of subjects with subthreshold disorders and different definitions of ASDs such as Asperger's Disorder or PDD-NOS, where the ADI-R algorithm score for social impairment may fall below the published clinical cutoff. Thus, our DSM-based structured interview for ASD may be useful and accurate for the assessment of ASD individuals across different cognitive and developmental levels with full and subsyndromal manifestations of these disorders.
Our results must be interpreted in the context of some methodological limitations. Since subjects in this study were referred for ASDs, our results may not generalize to other clinical and non-clinical settings. Because our sample consisted largely of Caucasian subjects, we do not know whether our results will generalize to other ethnic groups. The SRS is validated for youth ages 4 to 18 years but 4% (5/123) of our ASD sample was older than 18 years and received the scale. Although our DSM-based structured interview for ASD was DSM-III-R based, there have been very few changes between the DSM-III-R definitions of ASD and those in DSM-IV (see Table
1). Moreover, we documented a very high correspondence between the DSM-IV based clinician diagnosis of ASD and this instrument. Just as the current version of the structured interview is able to capture both DSM-III-R and DSM-IV diagnostic criteria, a revised version will capture DSM-V measures. As currently proposed, DSM-V criteria for Autism Spectrum Disorders are more narrow and unidimentional. As such, the DSM-based structured interview presented in this paper incorporates the criteria proposed in DSM-V. Coding criteria could also be altered in the future to encompass the changes proposed in the diagnostic criteria for ASD in DSM-V.
Competing interests (Conflict of Interest)
Gagan Joshi Disclosures: Ethel DuPont Warren Fellowship Award 2005-6; Pilot Research Award from the American Academy of Child and Adolescent Psychiatry 2005; National Institute of Mental Health (Reviewer and member of the NIMH Editorial Board); McNeil Pediatrics (CME sponsored by SynerMed Communications); Bristol Myers Squibb (Site PI for Multi-centered Trial); Glaxo Smith Kline (Site PI for Multi-centered Trial); Shire (Member of national advisory board)
Ronna Fried Disclosures: Dr. Fried has received honoraria from Shire.
Janet Wozniak Disclosures: Dr. Wozniak is the Author of "Is Your Child Bipolar" published May 2008, Bantam Books. Dr. Wozniak is a speaker for McNeil, Primedia/MGH Psychiatry Academy, and is on the Speakers Bureau for Lilly. Dr. Wozniak is on the Advisory Board/Consulting for Pfizer and Shire. Dr. Wozniak receives research support for McNeil, Shire, and Lilly. Dr Wozniak's spouse, John Winkelman, MD, PhD, is on the Speakers Bureau for Boehringer-Ingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, and Takeda, is on the Advisory Board/Consulting for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz Pharmaceuticals, Novartis, Neurogen, Novadel Pharma, Pfizer, UCB (Schwarz) Pharma, Sanofi-Aventis, Sepracor, and Takeda, and receives research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwarz) Pharma, Pizer, and Sepracor.
Jamie Micco Disclosures: Dr. Micco receives funding from the NIMH.
Aude Henin Disclosures: Dr. Henin has received honoraria from Shire, Abbott Laboratories, and AACAP. She receives royalties from Oxford University Press. She has also received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were, in part, supported though Independent Medical Education grants from pharmaceutical companies, including AstraZeneca, Lilly, McNeil Pediatrics, Shire, Forest Laboratories Inc., Sanofi aventis, Janssen, Bristol-Myers Squibb, and Pfizer.
Robert Doyle Disclosures: Speaker's honoraria- Shire, Novartis, McNeil, Neuroeducational Institute, MGH Academy, and APA. Advisory Boards- Shire, Novartis
Stephen Faraone Disclosures: Dr. Faraone has received consulting fees and has been on Advisory Boards for Eli Lilly and Shire and has received research support from Eli Lilly, Pfizer, Shire and the National Institutes of Health in the past year. In previous years, Dr. Faraone has received consulting fees or has been on Advisory Boards or has been a speaker for the following sources: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. In previous years he has received research support from Eli Lilly, Shire, Pfizer and the National Institutes of Health.
Joseph Biederman Disclosures: Dr. Biederman is currently receiving research support from Alza, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck, Organon, Otsuka, Shire, NIMH, and NICHD. In 2009, Dr. Joseph Biederman received a speaker's fee from Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth.
All other authors report no conflict of interests.
Authors' contributions
GJ participated in data analysis/interpretation, drafting article, critical revision, and data collection. CP participated in MA: statistics, drafting article, and critical revision. RF participated in concept/design and critical revision. JW participated in concept/design, data analysis/interpretation, and critical revision. JM, AH, RD, MG, MK, JC, and BM all participated in critical revision. SF participated in data analysis/interpretation, and critical revision. JB participated in concept/design, critical revision, and approval of article. All authors read and approved the final manuscript.