RTT adults with severe ID_Eur Psychiatry 2008 23 460.pdf

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European Psychiatry 23 (2008) 460e465 http://france.elsevier.com/direct/EURPSY/

Original article

Rett syndrome in adults with severe intellectual disability: Exploration of behavioral characteristics Johnny L. Matson*, Timothy Dempsey, Jonathan Wilkins Department of Psychology, Louisiana State University, 324 Audubon Hall, Baton Rouge, LA 70803, USA Received 24 February 2007; received in revised form 3 November 2007; accepted 5 November 2007 Available online 22 January 2008

Abstract Rett syndrome is a genetically linked form of autism spectrum disorder (ASD) accompanied by intellectual disability (ID). The disorder is also characterized by cardiorespiratory dysregulation, disturbance in muscle tone, reduced brain growth and scoliosis. Over 300 studies have been published on the disorder, most of which has focused on identification of causative factors, which appears to be the result of mutations of gene MECP2. Rarely have adults with Rett syndrome been studied, and behavioral characteristics in these individuals are largely unknown. The present study aimed to extend what little is known about behavioral characteristics of Rett syndrome in adults, with particular emphasis on social, communicative, and adaptive behavior. Rett syndrome adults with severe ID were matched to autistic adults with ID and ID only controls. The implications of these data for more fully describing and diagnosing the condition in adults are discussed. Ó 2007 Elsevier Masson SAS. All rights reserved. Keywords: Rett syndrome; Adults; Behavioral characteristics

Rett syndrome was first described in Vienna in 1966 [33]. The disorder is a severe neurodevelopmental disorder characterized by intellectual disability (ID), poor muscle tone, reduced brain growth, scoliosis, and cardiorespiratory dysregulation and caused by mutation in the MECP2 coding region [17,32]. The condition is one of five autism spectrum disorders (ASD) and as such shares behavioral characteristics with other disorders in the syndrome. A substantial literature is developing on the topic. The vast majority of studies can be described as genetic analysis of young children, primarily females [2,4e 6,15,18,41]. These data are very promising; however, genetic identification is not foolproof, particularly in milder cases [14]. Additionally, regression in skills is a hallmark of the disorder, although recovery of some communication, social and hand use skills often occurs [11,25]. Furthermore, while researchers recognize that autism and Rett syndrome are distinct conditions, some overlap in symptoms is evident [27].

* Corresponding author. Tel.: þ1 225 578 4104. E-mail address: [email protected] (J.L. Matson). 0924-9338/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2007.11.008

Given the variability in symptoms across time, across individuals and the fact that they overlap with other disorders, most notably ID and autism, points to the need for a better understanding and periodic evaluation of the behavioral characteristics for a given individual. Furthermore, while survival into adulthood is not uncommon for persons with Rett syndrome, the lack of research and variability in symptoms is largely unknown for adults with Rett’s [16]. Extrapolating from the child literature, it is likely that marked deficits in communication and functional skills persist [20,35]. However, direct testing is not only warranted but also essential. Establishing specific strengths and weakness of core symptoms is also underscored by the need for constant caregiver involvement that is required for persons with ASD in general and Rett’s syndrome in particular [12,13,37,39]. As a result, a better understanding of social, communicative, and adaptive skills, along with challenging behavior evinced by these adults is urgently needed. The purpose of this study then, was to assess these skill levels for adults with Rett’s syndrome and severe ID and to compare their skill deficits and strengths to adults with ID, and group with autism and ID.

J.L. Matson et al. / European Psychiatry 23 (2008) 460e465

1. Method 1.1. Participants Participants in this study were residents from one of two developmental centers in the southeast United States. Resident numbers for the two centers were 350 and 550, respectively. All adults who met the diagnostic criteria for Rett syndrome according to the DSM-IV classification system [1] at the facilities used in the study were included. These cases constituted all known adult cases of Rett syndrome in a catchment area of four million people. A total of 18 female adults diagnosed with profound mental retardation were selected for the study (Mean age ¼ 48.5, SD ¼ 9.4). Participants were divided equally into three groups: Rett, autism, and control (N ¼ 6 per group). Two psychologists independently evaluated each participant in the study individually. To receive a diagnosis of autism, the person had to meet DSM-IV and ICD-10 criteria for both psychologists’ evaluations [3,7,10,19,26]. The participants in the autism and control groups were selected to match the Rett group on the following characteristics: age, sex, level of mental retardation, and verbal ability. The latter two criteria were measured by individual administration of the Stanforde Binet intelligence test and the Vineland adaptive behavior scale [34,38]. 1.2. Autism spectrum disorderseproblem behavior adult The autism spectrum disorderseproblem behaviors for adults (ASDeBPA) is an instrument designed to identify problematic behaviors that are typically exhibited by individuals with ASD. The ASDeBPA measures three domains of behavioral impairment: aggression/destruction, disruptive behavior, and self-injury, with a composite total score also provided. The instrument contains 20 items on content related to verbal and physical aggression, self-injurious behavior, property destruction, and stereotypic behaviors. Raters were instructed to compare the target individual to a person their age residing in the community. Items were scored 0 ¼ not different, no impairment, or 1 ¼ different, some impairment. For the purpose of this study, only the composite total score was included in the initial analysis. The scale has good reliability, validity, and established cut-off scores [21]. 1.3. Vineland adaptive behavior scales (VABS) The VABS is a measure designed to assess personal and social functioning throughout the lifespan. Three domains of adaptive functioning are measured by the VABS. These include: communication, daily living skills, and socialization. Licensed PhD. level clinical psychologists and masters level clinical psychology students conducted the Vineland adaptive behavior scales with residential support staff. The Vineland consists of items in which the rater endorses 0 ¼ never performs behavior/never performs behavior independently; 1 ¼ sometimes performs the behavior/partially performs the behavior independently; or 2 ¼ usually performs the

461

behavior independently. Raters were instructed to rate each item depending on the target individual’s level of skill. Extensive research has been conducted utilizing the VABS as applied to ID and autistic populations [38]. 1.4. Matson evaluation of social skills for individuals with severe retardation (MESSIER) The MESSIER was designed to assess social skill functioning in persons with severe and profound mental retardation. It contains 85 items that are administered to the individual’s primary caregiver. The scale has well-established psychometric properties including reliability and validity. Factor analysis yielded six subscales which describe positive and negative social behaviors, as well as communication skills and nonverbal interaction skills. These six subscales are: positive nonverbal, positive verbal, general positive, negative nonverbal, negative verbal, and general negative. Informants were told to compare the target person to a person their age residing in the community. Items were scored 0 ¼ never, 1 ¼ rarely, 2 ¼ some, and 3 ¼ often. For the purposes of this study, only the general positive and general negative subscales were included in the initial analysis [22,23]. 1.5. Rett syndrome behavior questionnaire (RSBQ) The RSBQ is an informant-based instrument designed to measure behavioral symptoms that typically occur in individuals with Rett syndrome [28]. The questionnaire contains 100 items on content related to breathing difficulties, repetitive movements, sleeping problems, self-injury, and hand movements/hand skills. Raters were instructed to rate each item according to how well it described the target individual’s behavior over the last six months. Items were scored 0 ¼ not true, 1 ¼ somewhat or sometimes true, or 2 ¼ very true. Research has been conducted utilizing the RSBQ in determining the nature of behavioral symptoms exhibited in children with Rett syndrome [28]. 2. Results and discussion The data were analyzed using a multivariate analysis of variance (MANOVA) where diagnostic group was the independent variable with three levels: Rett, autism, and control. There were seven dependent measures; the total score on the ASDeBPA, the three domains on the VABS, two subscales from the MESSIER, and the total score on the RSBQ. We conducted a MANOVA to determine whether the groups differed on any of the seven dependent measures. Next, we conducted a series of one-way analyzes of variance (ANOVAs), one for each dependent measure, to show where the groups differed. All pairwise comparisons were made using the Tukey HSD test. Means are presented in Table 1. The results of the MANOVA revealed a significant main effect of diagnostic group, F(2,16) ¼ 2.589, p < 0.05. Therefore, we conducted an ANOVA with diagnostic group as the independent variable and the score on the ASDeBPA as the

J.L. Matson et al. / European Psychiatry 23 (2008) 460e465

462 Table 1 Mean scores from the behavioral measures Dependent measure

ASDeBPA total VABS communication domain VABS daily living skills domain VABS socialization domain MESSIER general positive MESSIER general negative RSBQ total

Diagnostic group Rett

Autism

Control

3.33 17.33 35.33 20.33 8.33 9.33* 16.5

5.33* 14.67 30.67 14.33* 7.67 11.67* 18.17

0.67* 20.33 41.67 29.68* 10.33 3.33* 11.33

*, p < 0.05. For VABS domains and the general positive subscale on the MESSIER; the lower score, the greater the deficit. For the ASDeBPA, the MESSIER general negative subscale, and the RSBQ total; the higher the score, the greater the deficit. All scores are reported as raw scores.

dependent variable. The analysis yielded a significant main effect of diagnostic group, F(2,16) ¼ 2.127, p < 0.05. Pairwise comparison revealed that significant differences occurred only between the autism group and the control group. A second ANOVAwas conducted with diagnostic group as the independent variable and the score on the socialization domain of the VABS as the dependent variable. A significant main effect of diagnostic group occurred, F(2,16) ¼ 5.31, p < 0.05. Pairwise comparisons showed that significant differences were only found between the autism and the control groups. Retts’ participant level of impairment fell between the other two groups. We conducted a third ANOVA with diagnostic group as the independent variable and the score from the general negative subscale of the MESSIER as the dependent variable. The analysis revealed a significant main effect of diagnostic group, F(2,16) ¼ 4.68, p < 0.05. Pairwise comparisons showed that significant differences were found between the autism group and the control group, and between the Rett group and the control group. The autism and Rett groups did not differ from each other. None of the remaining ANOVAs were significant. Additionally, an item analysis was conducted via a series of ANOVAs to determine which ASDeBPA, VABS socialization domain, and MESSIER negative subscale items elicited significant differences between diagnostic groups. ANOVAs were computed with diagnostic group as the independent variable and each item as a dependent variable. If a significant main effect was found, follow-up t-tests were conducted using the Tukey HSD test to determine where the differences emerged. For the ASDeBPA, significant differences between the autism group and both the Rett and control groups existed for items reflecting: playing with own saliva, aggression towards others, and repeated/unusual vocalizations. Significant differences emerged between the Rett group and the autism and control groups regarding mouthing/swallowing objects and elopement with individuals in the Rett group showing the highest rates of impairment. While all three groups evinced a significant difference from each other on the item reflecting repeated and unusual body movements, the individuals with autism had significantly higher rates of item endorsement as compared to Rett’s who had more symptoms than controls. Mean endorsement rates for items on the ASDeBPA are presented in Table 2.

For the VABS socialization domain, significant differences between the autism and control groups existed for items reflecting imitating simple movements, addressing familiar people by name, and sharing toys/possessions. Significant differences between the Rett and control groups as compared to the autism group emerged on items regarding saying ‘‘please’’ when asking for something and responding appropriately when introduced to strangers. Some items evinced differences between the controls and both the autism and Rett groups. These items contained content on apologizing for unintentional mistakes and having a best friend of the same sex. Mean endorsement rates for items on the VABS socialization domain are presented in Table 3. For the MESSIER general negative subscale, significant differences emerged between the autism group and the control group, as well as, the Rett and control groups for items reflecting: having trouble waiting for needs to be met, interrupting caregiver helping another, being timid/shy in social situations, demanding excessive attention/praise, and reacting poorly to correction. One item regarding doing the opposite of what an individual is told was significantly elevated for the autism group as compared to both Rett’s cases and controls. Mean endorsement rates for items on the MESSIER general negative subscale are presented in Table 4. While no significant differences emerged between diagnostic groups for the total RSBQ score, an item analysis was conducted to establish whether differences exist between diagnostic groups for specific behavioral symptoms. Significant differences emerged between the Rett and both the autism and control groups on items reflecting restricted repertoire of hand movements and not using hands for purposeful grasping. A significant difference was found between Rett’s cases and controls on the item regarding making repetitive tongue movements. Both the autism and Rett groups significantly differed from controls, though not from each other, on items reflecting Table 2 Percentage of items endorsed on the ASDeBPA that was significant at the 0.05 level (Rett vs. autism vs. control) Item description

% Endorsed % Endorsed % Endorsed by Rett by autism by control

Mouthing or swallowing 50* objects causing bodily harm Unusual play with objects 33.33* (e.g., twirling string, staring at a toy, etc.) Playing with own saliva 0* Leaving the supervision 33.33* of caregiver with permission (i.e., elopement) Aggression towards others 0* Repeated and unusual 0* vocalizations (e.g., yelling, humming, etc.) Repeated and unusual body 33.33* movements (e.g., handflapping, waving arms, etc.) This was seven of 20 items. *, p < 0.05.

0*

16.7*

33.33*

0*

33.33* 16.7*

0* 0*

33.3* 33.3*

0* 0*

66.7*

16.7*

J.L. Matson et al. / European Psychiatry 23 (2008) 460e465

463

Table 3 Percentage of items endorsed on the VABS socialization domain that was significant at the 0.05 level (Rett vs. autism vs. control)

Table 5 Percentage of items endorsed on the RSBQ that was significant at the 0.05 level (Rett vs. autism vs. control)

Item description

% Endorsed % Endorsed % Endorsed by Rett by autism by control

Item description

Imitates simple adult movements, such as clapping hands or waving good-bye, in response to a model Addresses at least two familiar people by name Says ‘‘please’’ when asking for something Shares toys or possessions without being told to do so Apologizes for unintentional mistakes Has a best friend of the same sex Responds appropriately when introduced to strangers

33.3

16.7*

50*

33.3

16.7*

50*

16.7*

0*

33.3

16.7*

16.7*

16.7*

33.3*

16.7* 33.3*

16.7* 0*

50* 33.3*

There are times when breathing is deep and fast (hyperventilation) Makes repetitive hand movements with hands apart Does not use hands for purposeful grasping Restricted repertoire of hand movement Makes repetitive tongue movements Tendency to bring hands together in front of chin or chest Rocks body repeatedly

16.7* 50*

This was seven of 66 items. *, p < 0.05.

16.7*

83.3*

% Endorsed by autism 66.7*

100*

% Endorsed by control 16.7*

33.3*

83.3*

16.7*

0*

83.3*

0*

0*

33.3

16.7*

83.3*

66.7*

33.3*

16.7*

83.3*

16.7*

50*

This was seven of 45 items. *, p < 0.05.

making repetitive hand movements and having a tendency to bring hands together in front of chin/chest. The autism group showed significant endorsement as compared to both Rett and control groups on items that contained content on hyperventilation and rocking body repeatedly. Mean endorsement rates for items on the RSBQ are presented in Table 5. Challenging behaviors such as physical aggression, selfinjury, and stereotypic behavior are prevalent as a whole across the population of individuals with ID and ASD [14]. Furthermore, it is generally agreed upon by ASD researchers that considerable overlap exists between Rett syndrome and autism [27,40]. In fact, until recently Rett cases were often regarded as autistic [29e31]. Nonetheless, for children developmental setbacks such as loss of hand skills and ataxic gait are specific to Rett’s [9]. Furthermore, genetic etiology differs with the bulk of Rett cases resulting from MECP2 gene mutation [36]. Autism on the other hand is rarely related to the MECP2 gene but as many as 2e10 other genes [8]. However, in adults with very severe ID, such as those studied here, skill

Table 4 Percentage of items endorsed on the MESSIER general negative subscale that was significant at the 0.05 level (Rett vs. autism vs. control) Item description

% Endorsed % Endorsed % Endorsed by Rett by autism by control

Has trouble waiting for needs to be met Interrupts teacher or caregiver helping another Does the opposite of what he/she is told Is timid or shy in social situations Demands excessive attention or praise Reacts poorly to correction

50*

This was six of 11 items. *, p < 0.05.

% Endorsed by Rett

33.3*

0*

33.3*

33.3*

0*

0*

33.3*

0*

66.7* 33.3* 33.3*

0* 0* 0*

50* 16.7* 33.3*

repertoires are much more limited than for persons with mild or no ID [21,24]. This issue can markedly complicate the diagnostic picture since there are relatively truncated skill repertoires to measure. Nonetheless these two conditions appear to be distinct and thus exploration of similarities and differences of symptom patterns appears warranted. This study therefore was designed to examine behavioral characteristics in individuals with Rett syndrome as compared to autism and ID and ID only. Overall, adults with autism exhibited greater frequency of problematic behavior as indicated by the scores on the ASDeBPA. Controls endorsed fewer items as compared to the Rett and autism groups. Individuals in the autism group had the highest rates of problem behavior endorsement on the ASDeBPA. However, mouthing or swallowing objects, causing bodily harm and elopement were particularly salient for the Rett cases. For the Rett cases, a general statement would be that behavior problems are not very common in these persons but are quite common in people with autism. Therefore, this presents as a salient differential diagnosis marker. Another finding of the current study was that individuals in the autism group showed less adaptive skills on the VABS socialization domain and the MESSIER general negative subscale. Item analysis demonstrated that individuals with autism had significantly higher amounts of impairment on these measures of social skills as compared to Rett’s cases which were more deficient than controls. Thus, adults with autism appear to show greater impairment in social skills functioning as compared to the Rett and control groups. Adults with Rett syndrome, autism, and ID could not be differentiated from each other on the VABS communication and daily living skill domains, the MESSIER general positive subscale and RSBQ total scores. These findings suggest that levels of adaptive functioning may be similar across diagnostic group regarding communication and daily living skills. While no overall differences in functioning were observed, unique

464

J.L. Matson et al. / European Psychiatry 23 (2008) 460e465

behavioral symptom patterns emerged via item analysis. Individuals with Rett syndrome evinced higher rates of hand skill deficiencies and repetitive tongue movements as measured by the RSBQ. This suggests that behavioral symptoms emerge which are unique to Rett syndrome. The overlap in Rett and autism symptoms compounded by severe ID could be a factor accounting for these results. Mount et al. (2002) were able to distinguish between Rett and severe ID. However, we had a much larger proportion of profound ID in our sample. Furthermore, they did not use an autistic group in their study. Another possible explanation is the fact that our sample was much smaller than theirs thus we did not have sufficient power to differentiate symptom clusters of autism and Retts. However, given the rarity of Rett syndrome in the first place and the fact that many of these afflicted persons do not reach adulthood, obtaining large samples, particularly where direct and extensive examination vs. mail out questionnaires are used, will be quite challenging. We surveyed all seven developmental centers in Louisiana, which has a population of four million people, and these were the only cases of Rett syndrome adults identified. Having said this, we did match our autism and control groups closely to those persons identified with Rett’s on as many characteristics as possible. There do appear to be salient behavioral differences in these groups with the ID only group being less impaired, Rett’s more impaired, and the autistic group most impaired. Furthermore, Rett syndrome does result in specific symptoms that are more severe and which help to define discrete behavior. These results are therefore promising and would suggest the value of further diagnostic research on the topic. References [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Washington, DC: APA; 1994. [2] Armstrong J, Pineda M, Aibar E, Gean E, Monros E. Classic Rett syndrome in a boy as a result of somatic mosaicism for a MECP2 mutation. Annals of Neurology 2001;50:692. [3] de Bildt A, Sytema S, Kraijer D, Sparrow S, Minderaa R. Adaptive functioning and behaviour problems in relation to level of education in children and adolescents with intellectual disability. Journal of Intellectual Disability Research 2005;49:672e81. [4] Bourdon V, Philippe C, Labrune O, Amsallem D, Arnould C, Jonveaux P. A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangement in Rett syndrome patients. Human Genetics 2001;108:43e50. [5] Braunschweig D, Simcox T, Savaaco RC, LaSalle JM. X-chromosome inactivation ratios affect wild-type MECP2 expression within mosaic mouse brain. Human Molecular Genetics Rett syndrome and MECP/þ 2 2004;13:1275e86. [6] Caballero IM, Hendrich B. MECP2 in neurons: closing in on the causes of Rett syndrome. Human Molecular Genetics 2005;14:R19e26. [7] Charman T, Taylor E, Drew A, Cockerill H, Brown JA, Baird G. Outcome at 7 years of children diagnosed with autism at age 2: predictive validity of assessments conducted at 2 and 3 years of age and pattern of symptom change over time. Journal of Child Psychology and Psychiatry 2005;46:500e13. [8] Folstein SE, Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nature Reviews: Genetics 2001;2:943e55. [9] Fombonne E, Chakrbarti S. No evidence for a new variant of MMRinduced autism. Pediatrics 2001;108:E58.

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