What happens to children who move off the autism spectrum? Clinical follow-up study

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1 Pediatrics International (2017) 59, doi: /ped Original Article What happens to children who move off the autism spectrum? Clinical follow-up study Nahit Motavalli Mukaddes, 1 Tuba Mutluer, 2 Basak Ayik 3 and Ayla Umut 1 1 Istanbul Institute of Child and Adolescent Psychiatry, 2 Child and Adolescent Psychiatry Clinic, Koc University Hospital and 3 Department of Child and Adolescent Psychiatry, Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey Abstract Background: There is controversial information on outcome of school age individuals who lose the diagnosis of autism and achieve optimal outcome (OO). The present study assessed the autism symptoms and other psychiatric disorders in a group of children with a past history of autism. Methods: The subjects consisted of 26 individuals who had lost the diagnosis of autism 2 8 years previously. Clinical assessment was done with both parents and children. Diagnostic and Statistical Manual of Mental Disorders (5th edn; DSM-V) criteria were used for diagnosis of autism spectrum disorder (ASD). In addition, Childhood Autism Rating Scale and Social Communication Questionnaire (current version) were used. Psychiatric disorders were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version (K-SADS-PL). Results: None of the participants met the criteria for ASD. Ninety-two percent had a lifetime diagnosis and 81% had a present psychiatric disorder based on the K-SADS. Attention-deficit hyperactivity disorder, specific phobia and obsessive compulsive disorder were the most common disorders. Conclusions: Improved status with regard to autism symptomatology is maintained over time, but these individuals are vulnerable to developing other psychiatric disorders. It is crucial to maintain psychiatric follow up of children who move off the autism spectrum. Key words autism, disorder, follow up, optimal outcome, psychiatric. Autism spectrum disorder (ASD) consists of a group of disorders characterized by impairment in reciprocal social interaction, communication, restricted interests, and stereotypical behaviors. 1 The developmental trajectories of children with ASD are heterogeneous. While a significant proportion of children with the diagnosis of ASD show slow improvement, some patients improve rapidly, 2 and a few studies have even reported on the loss of ASD diagnosis in some patients. 3 9 Up to 5 25% of children with a diagnosis of autism lose this diagnosis after appropriate intervention at an early age. 10 Children who lose the diagnosis of autism are considered to have achieved optimal outcome (OO). 6,10 There are only a few studies on OO in a group with a history of ASD, and there is a limited number of studies on clinical follow-up of this group several years after losing the diagnosis of autism. Zappella assessed 5 year follow up of 17 children who lost the diagnosis of autism. He reported attention-deficit hyperactivity disorder (ADHD) in 70% and tic disorder in 56% of the Correspondence: Tuba Mutluer, MD, Department of Child and Adolescent Psychiatry, Koc University Hospital, Davutpasa Street, No. 4, 34010, Topkapı, Fatih, Istanbul, Turkey. tubamutluer@gmail.com Received 10 July 2016; revised 11 September 2016; accepted 12 October patients. None of the patients met the criteria for autism diagnosis at follow up. 4 Fein et al. 6 identified 34 individuals aged 8 21 years with a past history of autism. They assessed the functioning of this group on several measures, and found that participants who achieved OO did not differ in socialization, communication, face recognition or most of the language measures compared with typically developing individuals. 6 The same authors assessed the psychiatric disorders in this group and reported high rates of ADHD and specific phobia. 11 A recent study, however, reported contradictory results. That study assessed psychiatric characteristics of 16 children aged 7 11 years who recovered from autism at the age of 4, following an educational program. They assessed this group using a semi-structured phone interview with parents. Three of 14 children again fulfilled the criteria for ASD, and six of them had sub-threshold ASD symptoms. 12 To summarize, there are few studies on school age and adolescent outcomes of individuals with a past history of autism, and there are conflicting results regarding autism symptoms in this group. We previously reported on the characteristics of an OO group. 9 In the current study, we examined the school age outcome of these individuals, who had achieved OO at least 2 years before this study and who were being clinically

2 Follow up of optimal outcome in ASD 417 followed up. The present study addressed the following issues: (i) whether the improved status with regard to autism symptomatology is maintained over time; and (ii) whether the children develop any other psychiatric problems requiring professional help. Methods Participants Original group Participants in the original study were regular patients of a psychiatry clinic, a referral center for developmental neuropsychiatric disorders. They were children who had previously received the diagnosis of ASD (autism disorder, n = 38; pervasive developmental disorder [PDD] not otherwise specified, n = 1) and did not meet the criteria for any ASD on follow up. All these children had diagnostic assessment and psychiatric follow up done in the same clinic. The children consisted of 30 boys and nine girls, aged months at referral. They lost the diagnosis of autism between 3 and 10 years old. All achieved OO following an early intervention program. The definition of OO followed Helt et al. 10 We considered that OO had been achieved if he/she met the following criteria at baseline: (i) Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) diagnosis of ASD at baseline; (ii) language delay; and (iii) total Childhood Autism Rating Scale (CARS) score >25.5 based on Chlebowski et al., 13 and these criteria at final assessment: (i) not meeting the DSM-IV criteria for any type of ASD; (ii) not needing special education for the core symptoms of autism; and (iii) total CARS 14 and Autism Behavior Checklist 15 scores in the non-autistic range, and intelligence quotient (IQ) in the non-impaired range (IQ > 78). All patients received early intervention. Two of the children were in early intensive behavioral intervention, and the rest were in a comprehensive individualized behavioral program. This program was inspired by pivotal response training. Therefore, in addition to special educators, home teachers and parents were actively involved in this education program. Higher IQ and early language development were identified as the most powerful factors contributing to OO in this group. More details on the characteristics of this group and the intervention program have been published elsewhere. 9 Procedure Two independent child psychiatrists with at least 7 years of experience in neurodevelopmental disorders reviewed the files, blind to the initial diagnosis. In addition to the OO group, they also reviewed the files of 15 children with another developmental disorder. All of the files of non-asd individuals were accurately rejected by the psychiatrists. In addition, the initial diagnosis of the ASD group was confirmed. The parents of prospective participants were informed about the aim of the study and were invited to take part in follow-up psychiatric examination. Informed consent was obtained from all parents before examination. All interviews and assessments were performed by an independent team consisting of two child psychiatrists and one clinical psychologist. Detailed psychiatric examination was done by the child psychiatrists, and IQ testing by the clinical psychologist (Fig. 1). Instruments Diagnosis of autism Detailed developmental and psychiatric assessments were done based on interview with parents and children. DSM-V criteria were used for diagnosis of ASD, but, given that the first diagnostic assessment of the group had used DSM-IV- TR, the same criteria again were reviewed for all subtypes of PDD. Clinicians rated the severity of autistic symptoms using CARS, 14 which has good sensitivity and specificity to distinguish ASD from non-asd and other developmental disorders. 13 In addition, parents rated the autistic features using Social Communication Questionnaire (SCQ, current version). 16 The SCQ is valid and reliable for Turkish children. 17 Psychiatric disorders Psychiatric interview was carried out with both children and parents. Psychiatric disorders were assessed based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version (K-SADS- PL). 18 The reliability and validity of the Turkish version of Present group Of the 39 individuals in the original study group, 26 lost the diagnosis of autism at least 2 years before the current study. These 26 individuals (21 boys, five girls; age, 6 16 years) were included in the present study. The characteristics of this group and the intervention program were assessed in a previous study. 9 In addition, psychiatric disorders at the time of OO were also reported in that study. 9 The current study focused on psychiatric status of this group several years after achieving OO. Fig. 1 Study design. CARS, Childhood Autism Rating Scale; K-SADS, Kiddie Schedule for Affective Disorders and Schizophrenia; OO, optimal outcome; SCQ, Social Communication Questionnaire; WISC-R, Wechsler Intelligence Scale for Children revised version.

3 418 NM Mukaddes et al. K-SADS-PL have been confirmed. 19 In addition missing information in the K-SADS was collected via file review. IQ Intelligence quotient was assessed using the Wechsler Intelligence Scale for Children revised version (WISC-R). 20 The reliability and validity of the Turkish version have been confirmed. 21 Statistical analysis All data were organized in Microsoft Excel SPSS version 18.0 for Windows (SPSS, Chicago, IL, USA) was used for statistical analysis. Results Subject characteristics Mean participant age was years, and 81% (n = 21) were boys and 19% were girls (n = 5). Mean age at OO was years. The mean time from OO to follow-up assessment was years. The mean total WISC-R score was ; detailed characteristics are listed in Table 1. ASD diagnosis None of the individuals met DSM-V criteria for, or had CARS scores indicative of, ASD ( ). In addition, the total SCQ score was in the non-autistic range (Table 2). During the interviews, all children were clinically judged to display age-appropriate levels of interaction with the examiner; four of them had verbal impulsivity and one of them experienced separation anxiety during IQ testing, but there was no social or communicative problems related to autism. Based on the information from their parents, all had social interaction with their peers. In individuals with ADHD there were some problems in maintaining friendships due to impulsivity in play. One child was described as na ıve by his mother. This 12-year-old boy lost the diagnosis of autism at the age of 10. His total IQ score was 73 and he was diagnosed with ADHD. His social clumsiness was related to ADHD and limitation in intellectual abilities. Table 1 Subject characteristics (n = 26) Range (mean SD) Age (years) 6 16 ( ) Gender (M/F) 21/5 Age at OO (years) 3 10 ( ) Time from OO to follow-up 2 8 ( ) assessment (years) Total IQ (113 20) IQ, intelligence quotient; OO, optimal outcome. Psychiatric disorders According to K-SADS and review of the patient files, 92.3% of the patients were diagnosed with one or more psychiatric disorders throughout their lifetime, and 80.7% had at least one psychiatric disorder at the time of follow-up assessment. The most common psychiatric disorders were ADHD, specific phobia and obsessive compulsive disorder (OCD; Table 3). Fifty percent of participants (n = 13) were on psychiatric follow up and all of them were receiving medication for ADHD, OCD, tics, and so on. Based on clinical assessment and WISC-R score, none of the children had intellectual disability (IQ range, ). All participants were attending a regular mainstream school. None of them was in a special education program for academic or social problems. Discussion This study assessed the psychiatric status of 26 children who lost the diagnosis of ASD 2 8 years previously. There are two major issues addressed in the study: whether the improvement in social and/or communicative areas persist for years after Table 2 Total CARS and SCQ scores Mean SD Total CARS scores Total SCQ scores CARS, Childhood Autism Rating Scale; SCQ, Social Communication Questionnaire. Table 3 Rate of psychiatric disorders based on K-SADS and medical records Psychiatric disorders K-SADS present % (n) K-SADS lifetime % (n) ADHD 53.8 (14) 69.2 (18) Specific phobia 46.2 (12) 46.2 (12) OCD 19.2 (5) 38.5 (10) Conduct disorder 3.8 (1) 7.7 (2) Eating disorders 3.8 (1) Nocturnal enuresis 3.8 (1) 3.8 (1) Tic disorder 3.8 (1) 19.2 (5) PTSD 3.8 (1) Acute stress disorder 3.8 (1) GID 3.8 (1) Anxiety disorder-nos 7.7 (2) GAD 7.7 (2) MDD 15.4 (4) Diagnosis based on Diagnostic and Statistical Manual of Mental Disorders (4th edn, text revision) criteria. ADHD, attentiondeficit hyperactivity disorder; GAD, generalized anxiety disorder; GID, gender identity disorder; K-SADS, Kiddie Schedule for Affective Disorders and Schizophrenia; OCD, obsessive compulsive disorder; PTSD, post-traumatic stress disorder; MDD, major depressive disorder; NOS, not otherwise specified.

4 Follow up of optimal outcome in ASD 419 recovery from autism, and whether they display other psychiatric problems after achieving OO. First, none of the children who had achieved OO earlier, currently met the criteria for an autism diagnosis or exhibited autistic symptoms. Therefore, the improved status of these children with regard to autism has been maintained for a number of years. This is similar to the Fein et al. 6 study, in which individuals with a past history of autism were found to have normal functioning in social and communicative areas later in life. Another study, however, showed that 29% of the children who lost the diagnosis of autism at the age of 4, met the criteria again for ASD in middle childhood. 12 This study differs from the present study methodologically. The diagnostic assessment in that study was based on phone interviews with parents. Gold standard assessment for diagnosis of autism is clinical interview with parents and direct observation of children. Additionally, while the participants of the other study received no psychiatric assistance following termination of treatment for autism, half of the present participants were on psychiatric follow-up after finishing their special education program. Therefore, the present group had a chance to benefit from psychiatric care even after finishing special education for autism. The remaining half, who were not in psychiatric follow up, also did not demonstrate any symptoms of autism. The second issue is the presence of other psychiatric disorders in this group. According to K-SADS and the additional information from patient files, 92.3% had at least one lifetime psychiatric disorder and 80.7% had a psychiatric disorder at the time of follow-up assessment. Therefore, the rate of psychiatric disorders decreased somewhat over time in this group but remained high. On final examination 19.3% did not have any psychiatric problems or behavioral complaints. Therefore, while some of the individuals with OO, at least at the time of examination, had no mental health problem, the majority of subjects still had some type of psychiatric disorder. Therefore, even after achieving OO and finishing educational or treatment programs for ASD, clinical follow up of this group should be continued for longer periods of time. With regard to the distribution of psychiatric disorders in individuals with OO, it appears that ADHD is the most common disorder. The presence of ADHD has been previously reported in similar patient groups. 5 Fein et al. 5 documented 11 patients who lost the diagnosis of autism and developed ADHD in early middle childhood. Various other studies reported ADHD as the most common psychiatric disorder in the recovery or OO group. 12,13 Given that most of the studies so far have reported ADHD as the most common psychiatric condition in children who recover from autism, it is possible that these two disorders are different manifestations of the same neurobiological entity. The relationship between autism and ADHD has been investigated in many studies due to the high rate of concordance between these two disorders. 22,23 Many other studies have detected significant clinical overlap and shared neurobiological factors between ASD and ADHD. According to these studies, although there are some common genetic and clinical feature between the two, there are some unique and non-shared factors that make these two disorders distinct In the present study only 53.8% of the previously autistic group had ADHD, and ADHD is not the only probable condition for individuals with OO, consistent with the view that they are distinct disorders. Another interesting finding is that the frequency of ADHD in the present group decreased over time: while 69.2% of them had a lifetime diagnosis of ADHD, on follow-up examination only 53.8% had current ADHD. This is consistent with previous research. 11 Specific phobia was the second most common disorder in this group. This finding is also consistent with previous research, in which ADHD and specific phobia were the most common psychiatric disorders. 11 The present rate of specific phobia was much higher than that in the Orinstein et al. 11 study. This could be related to the age differences between the subject groups. The Orinstein et al. study included older individuals (8 21 years old), compared with the present subjects (6 16 years old). Interestingly, the rates of K-SADS specific phobia in the initial and follow-up assessments were the same in the present study. It seems that there was a subgroup of patients who had an unrecognized specific phobia during clinical follow up and, as a result, no specific treatment was given for this particular problem. The third most common psychiatric disorder in the present group was OCD. Many studies with clinic-referred children and adolescents with ASD have reported high rates of OCD. 11,23 28 The previous reports on psychiatric disorders in OO or recovery do not report OCD in their subject groups. Given that compulsive behavior is part of ASD, it is often categorized as ASD rather than OCD. While 38.5% of the present children had an additional diagnosis of OCD in their past, only half of these (19.2%) fulfilled the OCD diagnostic criteria at final examination. The decrease in frequency of OCD seems to be related to implementation of interventions for OCD in this group. It is noteworthy that some psychiatric problems were not detected during K-SADS interview but were detected from review of the medical records. For instance, one male adolescent appeared to be free of psychiatric comorbidities according to the K-SADS but, when we examined his file, we found that he had a past history of gender identity disorder in preschool and middle childhood. Adding examination of medical records to the K-SADS interview minimizes the probability of missing any psychiatric disorders. Limitations The present study cohort consisted of a group of OO children mostly from the middle and upper socioeconomic classes, meaning that they had access to high-quality psychiatric care. Their parents were aware of their vulnerability to develop psychiatric or behavioral problems even after achieving OO. Fifty percent of them were on psychiatric follow up by an expert. Therefore, the group may not represent all children who achieve OO. Another limitation is that the study included

5 420 NM Mukaddes et al. mostly preadolescent children, with only a few adolescents. Therefore we cannot know what other psychiatric disorders they may develop later in life. The third limitation of the study was the lack of a control group including children with an ongoing ASD diagnosis. Strengths This group was on psychiatric follow up from the first diagnostic evaluation until losing the diagnosis of autism, therefore it was possible to detect any information that otherwise might have been missed during the current study. There was detailed information regarding diagnostic assessment and intervention programs, and a significant number of them had documented continuous clinical follow-up information until the final assessment. Therefore, the risk of missing important issues was minimal. In addition, the final assessment for autism diagnosis and other psychiatric disorders was performed by an independent clinicians who had no involvement in the previous diagnostic and intervention processes. In conclusion, although the improved status of children who achieve OO persists over time, they may develop other psychiatric disorders. Therefore, even after losing the diagnosis of autism and discontinuing an education program for autism, regular psychiatric follow up of these patients should be continued, and parents should be informed about the risk of other mental health problems in their children. Acknowledgment We are very grateful to Deborah Fein, PhD, who generously shared her brilliant ideas on this topic with us. Disclosure The authors declare no conflict of interest. Author contributions N.M.M. carried out regular clinical follow up, contributed to the conception and design of this study, and wrote and revised the manuscript; T.M. carried out clinical assessment at follow up, and performed the statistical analysis; B.A. carried out clinical assessment at follow up; and A.U. carried out WISC- R testing. All authors read and approved the final manuscript. References 1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edn. American Psychiatric Association, Washington, DC, Fountain C, Winter AS, Bearman PS. Six developmental trajectories characterize children with autism. Pediatrics 2012; 129: e Zappella M. Early-onset Tourette syndrome with reversible autistic behaviour: a dysmaturational disorder. Eur. Child Adolesc. Psychiatry 2002; 11: Zappella M. Autistic regression with and without EEG abnormalities followed by favourable outcome. Brain Dev. 2010; 32: Fein D, Dixon P, Paul J, Levin H. 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