Broader autistic phenotype in parents of children with autism: Autism Spectrum Quotient Turkish version

Psychiatry and Clinical Neurosciences 2013; 67: 20 27 doi:10.1111/pcn.12005 Regular Article Broader autistic phenotype in parents of children with autism: Autism Spectrum Quotient Turkish version Sezen Kose, MD, 1* Emre Bora, MD, 2 Serpil Erermiş, MD, 1 Burcu Özbaran, MD, 1 Tezan Bildik, MD 1 and Cahide Aydın, MD 1 1 Child and Adolescent Psychiatry Department, Ege University School of Medicine, Izmir, Turkey and 2 Melbourne University Psychiatry Department, Melbourne Neuropsychiatry Centre, Melbourne, Australia Aims: The Autism Spectrum Quotient (AQ) is a selfassessment screening instrument for measuring the degree to which an individual of normal intelligence shows autistic traits. Genetic factors could be responsible for the relatives of individuals with autism exhibiting higher than normal rates of autism-related impairments, referred to as the broader autism phenotype (BAP). The aim of this study was to test whether there is a difference between the parents of autistic and those of typically developing children (TDC) on AQ scores in a Turkish sample. Method: The AQ total and subscale scores of the 100 parents (47 fathers, 53 mothers) of children with autistic disorder (AD) were compared with the 100 parents (48 fathers, 52 mothers) of TDC. Results: The parents of AD children scored significantly higher than the TDC parents on total AQ score, and two of five subscale scores; social skills, and communication. The other three subscales (attention to detail, attention switching, imagination) did not differentiate groups. There was no significant difference between mothers and fathers on any AQ scores, neither in the AD nor TDC group. The group gender interaction was not significant on the total or the five subscale scores of AQ. Conclusion: Social skill and communication subscales differentiate AD parents more successfully, and are more sensitive, as reported in other studies. The present findings confirm that social skill and communication impairments in parents of children with autism spectrum disorders are indicators of BAP. Key words: autism, Autism Spectrum Quotient, broader autism phenotype. AUTISM SPECTRUM DISORDERS (ASD) are neurodevelopmental disorders characterized by deficits in social emotional functioning and communication, and by markedly restricted/repetitive interests and behaviors. 1 The first findings on the genetic basis of ASD came from twin studies. 2,3 In these studies it has been shown that if one monozygotic (MZ) twin has autism, not only is the likelihood of autism in the other twin greatly increased, but also that of the likelihood of other neurodevelopmental *Correspondence: Sezen Kose, MD, Ege Üniversitesi Tıp Fakültesi, Çocuk ve Ergen Psikiyatrisi Anabilim Dalı, 35040 Bornova-Izmir, Türkiye. Email: sezengokcen@hotmail.com Received 2 February 2012; revised 15 October 2012; accepted 28 October 2012. difficulties affecting language and social interaction. 4 In other words, beside the increased risk of autism in MZ twins, they have a concordance rate for mild autistic traits as high as 90%. 5 The twin studies thus led to the idea that the same genetic variants that put the child at risk for autism may also lead to a broad phenotype that can be seen in close relatives of people with autism. 4 It is suggested that genetic factors could be responsible for the relatives of individuals with autism exhibiting higher than normal rates of autism-related impairments, referred to as the broader autism phenotype (BAP). 6,7 The BAP is generally considered to be a subclinical set of characteristics or traits that index familiarity and/or genetic liability to autism. 8 This conception holds that the BAP is milder but qualitatively similar to the 20

Psychiatry and Clinical Neurosciences 2013; 67: 20 27 Broader autism phenotype and parents 21 diagnosed autism phenotype. 8 The characteristics of BAP were first observed by Kanner and Eisenberg, 9 and also reported in the twin study by Folstein and Rutter. 2 In the following family studies, it was reported that social and communication deficits, deficits in pragmatic aspects of communication, and/or ritualistic repetitive behaviors and some personality characteristics are more frequent among the relatives of autistic children. 10 13 The heritability of the BAP components was shown. 14,15 Bishop et al. noted the need for the identification of the traits that characterize the broad phenotype, and of reliable measures of these, for use in relatives. 4 Hitherto, at least three questionnaires, designed to measure the autistic features, were used to evaluate the BAP: the Social Responsiveness Scale (SRS), 16 the Autism Spectrum Quotient (AQ), 17 and the Broad Autism Phenotype Questionnaire (BAPQ). 18 The SRS is a 65-item questionnaire that explores emotionally appropriate reciprocal social interaction and communication in children. An adult informant completes it. Using the SRS, autistic traits have been reported to be higher in the siblings of children with autism. 19 The BAPQ was designed to measure the personality and language characteristics of the parents of autistic children. The BAPQ consists of 36 items and three subscales: aloof personality, pragmatic language deficits, and rigid personality. 18 The BAPQ has been validated using direct clinical assessment of BAP. 18 The adult AQ has been used extensively to measure BAP. The AQ is a self-assessment screening instrument for measuring the degree to which an individual of normal intelligence shows autistic traits. 17 Besides the adult version, child and adolescent versions are also available. 20,21 The AQ score is a good predictor of clinical diagnosis, 22 and correlations were found between ASD-related issues such as social attention 23 and brain function. 24 The AQ indicates high heritability. 14 It has also been translated into Turkish (AQ-TR), and has been shown to be reliable and have construct validity. The scale was also successful in demonstrating the male female discrepancy, which has been noted in other cultures. 25 The AQ is a quantitative measurement with a wide range of possible scores, and was developed to assess where an individual lies on the autism spectrum. 8 It is not time consuming, has been used extensively, has been shown to have consistent results across culture 26,27 and has been translated into Turkish. Because of these reasons we preferred to use this instrument. To our knowledge there are four studies that have used the AQ to compare the parents of children with autism with those of typically developing children (TDC). Bishop et al. suggested that AQ scores differentiate parents of children with an ASD from control parents on social skills and communication subscales. 4 Ruta et al. obtained similar results to Bishop et al.: 4 total score and communication, imagination and social skill subscales of the Italian version of AQ are higher in ASD parents. 28 Wheelwright et al. compared a sample of fathers and mothers of children with an ASD to fathers and mothers of TDC. 8 They found that both mothers and fathers of the diagnosed children scored higher than the control parents on total AQ score and on four out of five of the subscales (except the attention to details subscale). 8 Scheeren and Stauder did not find any differences on total or subscale scores of the AQ. 29 In two of these studies, there was a significant group gender interaction for these differences. 8,28 Ruta et al. reported that the higher scores in parents of ASD children in the imagination subscale were driven by mothers. 28 Wheelwright et al. reported a similar finding for AQ total score, imagination and attention switching subscales. 8 The previous studies, examining BAP using the AQ in parents of ASD children, examined parent control differences in heterogeneous clinical samples including autism (autistic disorder; AD), Asperger syndrome (AS)/high-functioning autism and pervasive developmental disorder not otherwise specified (PDD-NOS). Examining the children with AD might contribute to our knowledge because there might be differences in underlying genetic and neurobiological factors within the spectrum of ASD that could influence the pattern and characteristics of BAP in different groups. 30,31 Pickles et al. found that the severity of symptoms in verbal children with ASD was related to the degree of expression of the BAP in family members, but was unrelated in non-verbal affected children. 30 The aim of the present study was to test whether there is a difference between the parents of children with AD and those of TDC on AQ scores in a Turkish sample, and whether gender effects play a role in the expression of BAP phenotype in parents. METHODS Subjects The subjects consisted of the parents of children with classical AD accompanied by idiopathic mental

22 S. Kose et al. Psychiatry and Clinical Neurosciences 2013; 67: 20 27 Table 1. Subject demographic characteristics AD group TDC group P Age of children (years) 12.6 3.2 11.4 5.4 0.17 Gender of children, n (%) Male 43 (79.6) 47 (55.9) c 2 = 10.185 Female 11 (20.4) 37 (44.1) P = 0.001 Age of parents (years) 38.4 6.9 36.7 7.4 0.09 Age of mothers (years) 36.4 5.8 35.7 7.3 0.61 Age of fathers (years) 40.6 6.7 37.8 7.9 0.06 Gender of parents, n Male 47 48 c 2 = 0.020 Female 53 52 P = 0.89 Education years of parents 12.2 3.3 12.7 3.9 0.31 AD, autistic disorder; TDC, typically developing children. retardation, and the parents of TDC. All of the autistic children were recruited from the pool of outpatients of the Developmental Disorders polyclinic, with a diagnosis of AD, established in the Child and Adolescent Psychiatry Department of Ege University, Izmir, Turkey. We selected probands in the age range of 4 18 years with AD accompanied by idiopathic mental retardation. We limited the sample to subjects with a core diagnosis of AD because of concerns about distinguishing between conditions within the autism spectrum. Turkish adaptations of instruments such as the Autism Diagnostic Interview Revised 32 and the Autism Diagnostic Observation Schedule Generic 33 are not yet available. We clinically diagnosed mental retardation, depending on the developmental and clinical symptoms and functioning levels of the children according to age. This information was obtained using the form developed by the authors. The child s age, gender, developmental history, parents age, gender and educational years were noted on this form at the first evaluation. The children with AD who did not have any comorbid medical or neurological conditions such as Fragile-X syndrome, or phenylketonuria, were included in the study. A history of medical, neurological or genetic causes was the exclusion criterion for children. Fifty-four probands with AD according to DSM- IV-TR criteria, and 84 TDC were included in this study. The mean age of the AD probands was 12.6 3.2 years. The mean age of the control TDC was 11.4 5.4 years. There was no statistically significant difference between the mean age of the AD children and the control TDC. A total of 100 parents of AD children and 100 parents of control TDC were needed. There was no significant difference between the mean age of the parents of the AD group (38.4 6.9 years) and those of the TDC (36.7 7.4 years; P = 0.09). The mean age of the mothers of the AD probands was 36.4 5.8 years, and that of the fathers was 40.6 6.7 years. The control group consisted of 100 parents (52 mothers and 48 fathers) of 84 children, who had a child without any significant behavioral problems. The mean age of the mothers of the control group was 35.7 7.3 years, and that of the fathers was 37.8 7.9 years. There was no significant difference between the ages of mothers (P = 0.61, t = 0.51); and fathers (P = 0,06, t = 1.91) mean age (Table 1). The control group was matched to index parents for age, gender and educational level (Table 1). It is suggested that education is one of the most powerful predictors of premorbid IQ. 34 There was no significant difference between the mean age and between the mean years of education of the parents of ASD children and those of TDC. These control parents were recruited from among the hospital staff and their friends/ relatives. As expected in the AD group there was a male predominance. Procedure As stated in the previous section, 100 parents of autistic children and 100 parents of control TDC were needed. All of the children with autism were recruited from the pool of outpatients of the Developmental Disorders polyclinic, with a diagnosis of AD accompanied by idiopathic mental retardation. We obtained the diagnosis information from their files.

Psychiatry and Clinical Neurosciences 2013; 67: 20 27 Broader autism phenotype and parents 23 Initially, all of the parents (66 probands) of autistic children who did not have any comorbid genetic, medical or neurological conditions such as Fragile-X syndrome or phenylketonuria were interviewed by phone, email, or face to face during routine examinations of their child at the outpatient clinic. At the first stage, the children with autism, of whom the parents agreed to participate, were once again diagnosed for this study by a structured interview using the evaluation form developed by the authors and based on the DSM-IV-TR A-B, and C criteria of AD assessing the social functioning (five items), communication (four items), and stereotypic ritualistic behavior/interests (four items) domains. The child s age, gender, developmental history, parents age, gender and educational years were also noted on this form. The parents of 54 children of the 66 with AD agreed to participate. At the second stage, a second child psychiatrist who had 15 years experience with autistic children conducted the second diagnostic interview. The researchers gave the diagnosis of AD for children according to DSM-IV-TR criteria, by consensus. Among the parents, 46 couples and eight single parents (seven mothers, one father) agreed to participate. None of the parents had a history of psychiatric treatment. The final index group consisted of 100 parents (53 mothers and 47 fathers) of 54 probands with AD according to DSM-IV-TR criteria. All included parents completed the AQ-TR. The AQ is a brief, easy to use and score, self-reported questionnaire for assessing the broader phenotype in adults of normal IQ. It consists of 50 questions, made up of 10 questions assessing five different areas: social skill; communication skills; imagination abilities; attention switching; and attention to details. Each of the items listed here scores 1 point if the respondent records the abnormal or autistic-like behavior either mildly or strongly. 17 The higher the score on the AQ, the more autistic traits the individual has. The AQ was translated into Turkish (AQ- TR) by Köse et al. 25 The AQ-TR was completed by 406 university students (58% female, 42% male). To show the reliability of the Turkish version of the AQ (AQ-TR), Cronbach s alpha and test retest reliability were evaluated for the university students. Factor analysis was used to test the construct validity of the scale. Cronbach s alpha for the scale was 0.64. Test retest reliability of the scale was satisfactory (0.72). All subscales were in correlation with the total score of the scale. The total score and subscale scores of AQ-TR did not correlate with age (r =-0.10 0.07, P = 0.06 0.84) or duration of education (r =-0.10 0.02, P = 0.06 0.99). The total score of the AQ-TR (P = 0.003) and the scores of social skills (P = 0.001), communication (P = 0.034), and imagination (P = 0.002) subscales were higher in men. AQ-TR was found to be a reliable instrument. Parents were encouraged to fill in any missing questions, which were detected during the collection of questionnaires. Control subjects were interviewed using the Child Behavior Checklist (CBCL) 35,36 to exclude those parents who had a child with behavioral or developmental problems. 37 40 The Turkish version of the CBCL is a self-administered parent-report questionnaire that contains 20 competence and 118 problem items. The competence scales are Activity, Social, and School. The problem scales are Aggression, Anxiety/ Depression, Attention Problems, Delinquency, Social Problems, Somatization, Thought Problems, and Withdrawn. The 118 problem items describe a wide array of problems that are rated on a 3-point scale. Parents score each item 0, 1, or 2 (not true, somewhat true, or very true). The test retest reliability of the Turkish form was 0.84 for Total Problems, and the internal consistency was adequate (Cronbach s alpha = 0.88). 35,36 The children who score 0 66 are considered to be without behavioral or developmental problems. A history of psychotic disorders and history of psychiatric treatment were the exclusion criteria for all subjects. Control subjects had no family history for autism/as and schizophrenia. As stated, the control group consisted of 100 parents (52 mothers and 48 fathers) of 84 TDC. The research protocol was approved by the Ege University Faculty of Medicine, Child and Adolescent Psychiatry Department Academic Committee. The participants were individually briefed on the aim of the study and signed an informed consent form in accordance with the Declaration of Helsinki. Statistical analysis Statistical analysis was conducted using SPSS 16.0 (SPSS, Chicago, IL, USA). Between-group differences were examined using univariate analysis of variance. For the AQ-TR and its subscales, two-way ANOVA (group and gender) was performed because previous evidence suggest that there might be gender differences for the AQ-TR. If a tendency for a gender proband diagnosis interaction effect was observed, pairwise t-tests were also conducted. Pearson

24 S. Kose et al. Psychiatry and Clinical Neurosciences 2013; 67: 20 27 Table 2. AQ-TR mean scores AD parents (n = 100) TDC parents (n = 100) Group effect Gender effect Group Gender interaction Fathers Mothers Fathers Mothers (n:47) (n:53) (n:48) (n:52) AQ scores mean SD mean SD mean SD mean SD F P F P F P Total score 19.08 4.4 18.85 6.5 17.5 4.8 17.15 5.7 4.49 0.035 0.12 0.72 0.01 0.90 Social skills 4.04 1.8 4.00 1.9 3.23 1.9 3.43 1.9 6.80 0.010 0.15 0.70 0.16 0.69 Attention switching 4.02 1.8 3.81 1.8 3.44 1.7 4.1 2.0 0.42 0.52 0.88 0.35 2.51 0.12 Attention to detail 4.89 2.2 4.67 2.2 4.98 2.0 4.39 1.7 0.42 0.84 1.63 0.20 0.25 0.62 Communication 2.36 1.5 2.71 1.9 2.08 1.3 1.69 1.3 7.83 0.006 0.06 0.81 2.36 0.13 Imagination 3.76 1.6 3.65 2.1 3.81 1.9 3.51 2.0 0.11 0.75 0.53 0.47 0.25 0.62 Univariate analysis of variance (statistical significance set at P < 0.05). AD, autistic disorder; AQ-TR, Autism Spectrum Quotient Turkish version; TDC, typically developing children. correlation test was used to determine the relationship between variables. We used multiple regression analysis to explore the predictors of the AQ-TR total and five subscale scores. We considered P < 0.05 to be statistically significant. RESULTS The mean AQ-TR total and subscale scores and standard deviations are given for both mothers and fathers of the two groups in Table 2. Univariate analysis of variance, for between group (AD parents vs. TDC parents) and gender, was carried out for the total and five subscale AQ-TR scores. There was a significant main effect of group, with the AD parents scoring higher than the TDC parents on total AQ-TR score (F = 4.49, P < 0.03), and social skills and communication subscale scores (Table 2). There was no significant main effect of gender on total AQ-TR score (F = 0.12, P = 0.72) or on the five subscale scores. We did not find a significant difference on any AQ-TR scores between mothers and fathers in AD nor in the TDC group. The group gender interaction was not significant on the total (F = 0.01, P = 0.90) or the five subscale scores of the AQ-TR (Table 2). The social skill subscale score was significantly higher in fathers of probands (P = 0.03) than fathers of TDC, and the communication subscale score was significantly higher in mothers of probands (P = 0.003). Parental education, parent age, and gender were not significantly correlated with the AQ-TR total or the five subscale scores (parent age: r, -0.003 to 0.091; parent gender: r, 0.016 to -0.096; parent education level: r, -0.012 to -0.111). We used multiple regression analysis to explore the predictors of the AQ-TR total and five subscale scores. Each of these multiple regression models using the independent variables parent age, gender or education level were statistically insignificant (AQ-TR-total, P = 0.857; social skills, P = 0.975; communication, P = 0.797; attention switching, P = 0.579; attention to detail, P = 0.737; imagination, P = 0.928). DISCUSSION The primary goal was to investigate whether parents of children with AD have higher rates of autistic traits and BAP in comparison to parents of control TDC in a Turkish sample. The cross-cultural stability of the AQ as a measure of BAP and the confirmation of the genetic liability for autism are the main strengths of the study. We found that the parents of AD children scored higher on total score and on two subscale scores (social skills, and communication) of the AQ-TR than the parents of TDC. The present results are consistent with those of Bishop et al. and Ruta et al. 4,28 Scheeren and Stauder reported that social skills and communication subscale scores differentiated parents of children with ASD from control parents. 29 Ruta et al. (but not Bishop et al. 4 ) found higher scores on total score of AQ. 28 Wheelwright et al. found that both mothers and fathers of the ASD-

Psychiatry and Clinical Neurosciences 2013; 67: 20 27 Broader autism phenotype and parents 25 diagnosed children scored higher than the control parents on total AQ score and on four out of five of the subscales. 8 We did not find a difference in attention to detail, attention switching, or imagination subscale scores of the AQ-TR. The more consistent result of these studies is the higher scores of the parents of ASD children on social skill and communication subscales, as in the present results. Wheelwright et al., however, found higher scores also on the attention switching and the imagination subscales in the ASD group. 8 This might be explained by the better power of that study to detect subtle between-group differences due to the larger sample size. To our knowledge there is only one study in the literature that did not find any significant difference between the parents of autistic children and controls. 29 They compared 25 parents who had an autistic child to 25 control parents. They emphasized, however, the limitations of the self-report instruments, such as giving socially desirable answers rather than answers that most closely resembled their personal beliefs and capabilities, and the need of the parents with an autistic child to present themselves as non-autistic. Also, their sample size was small. Those authors also used a 4-point Likert scale instead of a 2-point one. The difference in rating type may have influenced the result. Furthermore the present participants differ from those in the other studies. We included only autistic children with idiopathic mental retardation. We found that, even in different cultures, social skills and communication subscales are the most sensitive subscales to differentiate AD parents from control parents, as reported in other studies. 4,28 Although the earlier studies found gender differences in normal adults, men scored higher on overall AQ, and also had poorer social skills, and communication. 17,26,27,41 It is important to determine whether the gender effects play a role in the expression of BAP phenotype in parents. Wheelwright et al. and Ruta et al. reported that there was a significant group gender interaction for these differences. 8,28 Ruta et al. reported that higher scores in parents of ASD children on the imagination subscale were driven by mothers. 28 Wheelwright et al. reported a similar finding for AQ total score, imagination and attention switching subscales. 8 In the present study we did not find a sex difference on any scores of the AQ-TR, neither in the AD nor the TDC parent group between the women and men. There was no significant main effect of gender on AQ-TR score. The group gender interaction was not significant on the total or the five subscale scores of the AQ-TR. In this study we found that the gender differences did not explain the group differences on AQ-TR scores. This could be due to the sample size, sample type, or limitation of the self-report instrument. Autistic features appeared to be more frequent in normal men, and seem to be an extension of personality discrepancies between male and female rather than an association with autism. Baron-Cohen et al. determined that the mean AQ score was 15.4 for women and 17.8 for men in the general population. 17 In our previous study, the total score of the AQ-TR was found to be higher in male than in female subjects (18.76 and 17.23, respectively) in the Turkish population. 25 Although the scores for Turkish men and women were higher than those from the UK, a similar condition was reported for the Japanese version. 26 In the current study, total AQ-TR score of parents of TDC was 17.15 for mothers, and 17.5 for fathers. Also our previous study demonstrated the gender differences as expected, but the present study failed to show this. The power of this study may not be sufficient to detect the small differences, given that we found gender differences in our previous study with a larger sample size using the AQ-TR (total AQ-TR score, P = 0.003; social skills score, P = 0.001; communication score, P = 0.034; and imagination score, P = 0.002 were higher in male subjects). 25 In the present study the mothers of the TDC scored higher than a general population sample from the UK but similar to our first study. But the fathers of TDC scored similar to TDC mothers, not higher. Their scores were also lower than the scores in the previous study. Here there may be sampling bias. The present subjects were children with AD and idiopathic mental retardation. These children may have other deficits differing from ASD traits, and this could be reflect in the results. The effect of intellectual dysfunction could be considered as a limitation and as a sampling bias in the present study. Conclusion The cross-cultural stability of the AQ as a measure of the BAP and the confirmation of the genetic liability for autism are the main strengths of the study. The present results replicate the findings for the English version of the AQ to assess BAP, in a Turkish sample. We found that, even in different cultures, social skill and communication subscales are the most sensitive

26 S. Kose et al. Psychiatry and Clinical Neurosciences 2013; 67: 20 27 subscales to differentiate the AD parents from control parents, as reported in other studies. 4,28,30 Other studies have reported that social skill and communication impairments in parents of children with ASD are known as an indicator of BAP. 11,12,28,31,42 The social skill and communication deficits may be related to genetic risk for autism, but to make a conclusion by applying a self-reported questionnaire to two groups and comparing them, is not possible. More detailed studies including neuropsychological and genetic examinations are needed in this area. The present findings confirm these results, especially for the total score, and the social skill and communication domains of the AQ. ACKNOWLEDGMENT None of the authors has a conflict of interest. REFERENCES 1. American Psychiatric Association. Diagnostic and Statistical Manuel of Mental Disorders, Fourth Edn. (DSM-IV). APA, Washington, DC, 1994. 2. 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