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J. Indian Assoc. Child Adolesc. Ment. Health 2014; 10(4):271-291

Original Article

Broader phenotype in autism- an adaptation of two measures in a clinical sample

Preeti Jacob, M.V. Ashok

Address for correspondence: Dr. Preeti Jacob, Senior Resident, Department of Child

and Adolescent Psychiatry, National Institute of Mental Health and Neuro Sciences

(NIMHANS), Bangalore E-mail: preetijacob@gmail.com

Abstract

Introduction: The importance of genetic factors in autism is on relatively firm grounds,

but the definition of the phenotype for use in genetic studies continues to evolve. We

report on our exploration of broader phenotype amongst relatives of individuals with

autism using the Social Responsiveness Scale (SRS) and the Autism Spectrum Quotient

(ASQ). Methodology: The scales were administered either in English or in the Kannada

adaptation to 30 siblings and parents of autistic children, 25 siblings and parents of

children with a psychiatric disorder and 30 children with no psychiatric morbidity and

their parents. Results: Both paternal and maternal ASQ scores were significantly higher

in the Autism Group as compared to the Psychiatric and Normal Control groups. On the

ASQ, qualitatively the factors that were more discriminatory were social skills and

attention switching. Siblings of children with autism scored significantly higher on the

SRS Total Scoresand the factor scores of social awareness, social communication and

social motivation, as compared to the siblings of children with a psychiatric disorder and

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normal controls. Conclusion: The Social Responsiveness Scale and the Autism Spectrum

Quotient have the potential to identify the broader phenotype in autism in the Indian

context and further exploration in community samples is justified.

Key words: Broader phenotype in autism, Social Responsiveness Scale, Autism

Spectrum Quotient

Introduction

Autism is a behavioural syndrome characterised by social deficits, communication

abnormalities and stereotyped or repetitive behaviours. Over the last two decades,

evidence from twin and family studies has consistently pointed to a strong genetic

aetiology. The risk of recurrence of autism in siblings has been estimated at 6-8% [1-4].

Twin studies have also shown much higher concordance rates among monozygotic twins

than among dizygotic twins [5]. Family members of autistic probands were also found to

have difficulties in the three major areas of impairment implicated in autism, although

they did not meet criteria for pervasive developmental disorders. Hence, broader

phenotype in autism evolved as a concept from these twin and family studies [6,7]. The

broader phenotype in autism refers to the mild, non-pathological autistic characteristics

among relatives of people with autism [8]. These milder deficits in the relatives of

autistic individuals that are qualitatively similar to autism but not sufficient enough to

diagnose autistic spectrum disorder have also been termed as the “lesser variant of

autism”, the narrow and broad phenotype being the gradient of these milder deficits[7]. It

is generally accepted that autism is a genetically heterogeneous condition. In order to

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increase the power of genetic studies, increasingly behavioural phenotypes are being

included. Various measures are being used to tap these behavioural phenotypes [7,9, 10,

11, 12]. Demonstrating a valid broader phenotype will permit such measures to be used

in molecular genetic analysis, thereby increasing the sensitivity of such studies to detect

the potential genes operating in autism. In India we have access to large extended

families. Hence, this provides a unique opportunity to test for broader phenotypes in

autism. A valid and reliable way of determining the broader phenotype in autism has not

been explored in India. There are no measures currently available in the Indian context to

explore the broader phenotype in autism. The study aims to adapt the Social

Responsiveness Scale and The Autism Spectrum Quotient to the local context and

evaluate if these measures could demonstrate a valid broad phenotype in autism in the

Indian context.

Methodology

Sample:

As shown in table 1, the sample consisted of three groups namely, siblingsand parents of

autistic probands (Autism Group) (n=90; that is 30 siblings and 60 parents), siblings and

parents of children with other psychiatric disorders including disruptive behaviour

disorders, anxiety disorders, dissociative disorders and somatoform disorders (Psychiatric

controls) (n=73; that is 25 siblings and 48 parents)) and children with no psychiatric

morbidity and their parents (Normal controls) (n=90; that is 30 siblings and 60 parents).

Children between the ages of 6-17 years, belonging to either gender, were included in the

study. Parents who were less than 55 years of age, who did not suffer from any

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neurological illness, spoke English or Kannada, gave consent and who lived with the

children were included in the study. In the normal control group, only children with

siblings were included to tap the sibling experience. The autistic probands and the

children with psychiatric disorders were identified from the St. John’s Medical College

Hospital Psychiatry Out Patient Department. The children who had no psychiatric

morbidity were recruited from community sources. Purposive sampling was used and the

socio-demographic profile was matched as far as possible.

Measures:

The Social Responsiveness Scale (SRS) is a 65 item questionnaire that ascertains autistic

symptoms as quantitative traits in children aged 4 to 18 years. In the present study the

parent report measure was used. It measured the social impairment across naturalistic

social settings. The questions focussed on the child’s behaviour in the past 6 months and

includeditems that ascertained social awareness, social information processing, capacity

for reciprocal social responses, social use of language and stereotyped/ repetitive

behaviour and preoccupations. The five factors that were measured were social

awareness, communication, motivation social cognition and mannerisms. It was rated on

a Likert scale from “0” (never true) to “3” (almost always true). Higher scores indicated

greater severity of social impairment [13]. Scores on the SRS are highly heritable,

generally unrelated to I.Qand continuously distributed in the population [14, 15].The

psychometric properties of the measure are good [16]. In this study the measure was

used to unearth the broader phenotype in autism in siblings and to achieve discriminant

validity for the measure in the Indian context.

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The Autism Spectrum Quotient (ASQ) has 50 itemsdivided into five subscales, namely:

social skills, communication, imagination, attention to detail and attention

switching.Each item scores zero or one, with one point being awarded if the participant

chooses the 'autistic trait' response. The Autism spectrum quotient produces near normal

distribution in the normal population [17].In this study it was used to identify the broader

phenotype in autism in the parents, and adapt and explore the discriminant validity of the

measure in the Indian context.

Procedure:

The SRS and ASQ were translated into Kannada and the translation was formalised

following standard principles of back-translation and modifications, with the help of two

non-clinical bilingual experts. A fixed number of clarifications per question were agreed

upon and adhered to throughout the study. The scales were administered either in English

or in the Kannada adaptation. The ASQ was administered to each parent by the 1st author

to maintain uniformity, although it is a self-report measure. The Social Responsiveness

Scale – parent report was administered to either parent by the 1st author to assess the

children and adolescents included in the study. The children were also directly assessed

by the 2nd author to rule out autism using the Childhood Autism Rating Scale (CARS)

[18]. The children were also evaluated for any psychiatric morbidity with the help of a

clinical interview and the Strengths and Difficulties Questionnaire (SDQ) [19]. The 2nd

author determined group membership. The 1st author who administered the scales,

namely the SRS and the ASQ, was blind to the group membership until the completion of

data collection.Informed consent was obtained in writing from all the participants before

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inclusion in the study. The study was reviewed and approved by the Ethics Committee,

John’s Medical College Hospital.

Results

The children included in the study from the three groups assessed did not meet the

criteria for autism (on the CARS and clinical interview ) and were below the

international cut off for likely emotional and behavioural disorders as measured by the

SDQ and clinical interview. All children enrolled in the study were above the 50th

percentile on the UK norms of the Raven’s Coloured and Standard Progressive Matrices

(CPM and SPM), which were administered by the 1st author [20].

The mean ages of the fathers in the study was 43.02± 4.64 years, that of the mothers was

37.6±5.41 years and 10.79±2.77 years for the siblings. 57.6 %( 49) of the siblings

studied were females. There were more females studied in the Autism (17/30) and the

Psychiatric Control Group (17/25) than in the Normal Control Group (15/30), but this

difference was not statistically significant.

As shown in table 2, there was no significant difference between the three groups in the

years of schooling of father and mother. (p> 0.05). One way ANOVA technique was used

to compare between the three groups.

As shown in table 3, there was no significant difference between the I.Q scores of the

siblings in the three groups studied (F=1.385, p=0.256).

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As shown in table 4, there was no significant difference in the ASQ scores based on the

gender of the parent in all three groups.

As the standard deviation was high and very close to the mean the sample was considered

non normal. Therefore, median and inter- quartile range was chosen to compare between

the groups. Kruskal Wallis analysis was done.

As can be seen from Table 5, the median ASQ scores were significantly higher in the

parents (both fathers and mothers) of children with autism (Autism Group) as compared

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to the median scores of parents from the Psychiatric control group and the Normal control

group and this difference between the groups was statistically significant. However, the

median scores were not significantly different between the Psychiatric control group and

the Normal control group.

There is a moderate positive correlation between years of schooling of parents and their

respective ASQ scores which was statistically significant (Table 6).This shows that as the

years of schooling increased the scores on the ASQ also increased.

The parents (both fathers and mothers) who answered the English questionnaire had

higher mean ASQ scores and the difference between the scores based on the language of

the questionnaire was statistically significant (Table 7).

As shown in table 8, those parents who answered the English questionnaire also had more

years of education and higher ASQ scores and the difference between the groups was

statistically significant.

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Table 9 shows the mean and SD of the Total SRS scores. The mean SRS scores were

significantly higher in the Autistic group as compared to the Psychiatric control group

and the Normal control group. The total mean SRS scores for boys was 6.30±5.5 and for

girls was 4.43±4.53. Although the mean scores were higher in boys it was not

statistically significant (t= 1.722, p=0.09).

As the data was considered non-normal, median and interquartile ranges were used to

compare between the groups (Table 10). Median and inter- quartile ranges were used as

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the sample was considered as non-normal. Mann Whitney U test was used to compare

between two groups. As can be seen from table 10, the median total SRS raw scores in

the Autism group was significantly higher than the scores in the Psychiatric control group

and the Normal control group and this difference between the groups was statistically

significant. The individual factor scores were significantly higher in the Autism group

when compared to the Psychiatric control group and the Normal group for the factors of

awareness, communication and motivation and this difference between the groups was

statistically significant. However, the factor scores for cognition and mannerisms were

not statistically significant in the Autism group when compared to the other two groups

(p=0.33; p=0.55 respectively). There was no significant difference in the scores based on

the language of the questionnaire used (p=0.63). Mann Whitney U test was used.

Discussion

The study aims to demonstrate a valid broad phenotype in family members of autistic

probands in the Indian context using two English based measures. Our aim was to adapt

the Social Responsiveness Scale (SRS) and the Autism Spectrum Quotient (ASQ) to the

local context and establish discriminant validity, which examines a measures’ ability to

discriminate between populations that are expected to differ on the construct of interest.

The strengths of our methods were that two clinical experts were involved in ensuring

conceptual congruence of various items, after reviewing the back-translated version. The

adapted version therefore had face validity. A fixed format with specific number of

clarifications was adhered to throughout the study. Although the Autism Spectrum

Quotient (ASQ) is a self- report measure, it was formally administered by the 1st author to

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all the parents irrespective of language and educational qualifications to maintain

uniformity. The limitation was that a more formal validation of the two measures was not

carried out.

Indian norms are not available for the ASQ and the SRS. There was no significant

difference in the socio-economic and the educational status in the three groups. However,

the ASQ scores of parents differed significantly when Kannada and English speaking

subjects were compared across the three groups (Table 7and 8). There was also a

significant difference in the years of education in the two groups divided on the basis of

language of the questionnaire. The authors of the Autism Spectrum Quotient have also

demonstrated a difference in scores based on the education status. They have shown that

those who had more years of education and engaged in careers in science and engineering

scored closer to the autistic end of the spectrum than those working in the arts [17].We

believe that the years of education explain the differences in the ASQ scores between the

Kannada and the English questionnaire groups rather than the differences in the two

questionnaire versions.

The children were screened for psychiatric and developmental disorders by the 2nd

author, but the parents were not formally screened for a psychiatric disorder. The children

enrolled in the study were screened by the 1st author for intellectual disability using CPM

and SPM. In our sample, the number of parents with a known psychiatric disorder was

very small, and there were no differences across the three groups with regard to their

distribution. In this context it is useful to consider the samples used in other studies. Most

of the studies using the Social Responsiveness Scale have compared siblings of children

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with autism to typically developing children [21]. Psychiatric controls have also been

used as the Social Responsiveness Scale distinguishes children with Pervasive

Developmental Disorderfrom those with a psychiatric disorder [22].This finding has been

replicated in our study. As autistic traits fall along a behavioural continuum, we included

all three groups in our study.

ASQ findings:

A previous study, by Dorothy Bishop and colleagues [23],suggested that ASQ scores

differentiate parents of childrenwith an Autism Spectrum Disorder (ASD) from control

parents on two subdomains:communication and social skills.A similar study by

Wheelwright et al[24], with a much larger sample size, demonstrated that parents of

children with autism scored higher than parents of typically developing children in four

out of the five subscales, except the subcategory “attention to detail” on the ASQ.Our

study supports the findings of both the above studies, as when the scores on individual

items were compared, parents of children with autism scored more on the items

pertaining to social skills, communication, imagination and attention switching. Not

many parents acknowledged the items pertaining to the subcategory “attention to detail”.

In our study there were no significant differences between the ASQ scores of fathers and

mothers (Table 4). This finding differs from previous studies, which have shown that

men fall closer to the autistic end of the spectrum than women [17, 24]. The inability of

the construct to demonstrate gender differences can be taken to question its validity in our

context. This may be due to sampling differences, particularly educational levels, which

are seen to impact ASQ scores. As the overall number of items which were accepted by

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participants in all three groups was low, we did not look for statistical differences in the

various sub-factors in the ASQ. The scores were also much lower than expected. Hence,

one of the other possibilities could also be that parents gave socially desirable

answersrather than answers that most closely resembled theirpersonal beliefs and

capabilities. It could be that parents with an autistic child felt the need to present

themselves asnon-autistic. This may have hidden a true difference inautistic

characteristics between the groups. One possibleway to overcome this problem in the

future, is not to relyon self-reports alone, but also to include a version of theASQ where

parents have to rate their spouse [25].

SRS findings:

In our sample, the median total SRS raw scores and three factor scores namely social

awareness, social communication and social motivation were significantly higher in the

Autism group compared to the scores in the Psychiatric control group and the Normal

control group (Table 10). This supports the findings of other studies where sibling SRS

scores were continuously distributed and substantially elevated for both the autistic and

pervasive developmental disorder groups. The scores were the highest in the (i.e. greatest

impairment) siblings of autistic probands from multiple-incidence families, followed by

siblings of probands with any pervasive developmental disorder, and then siblings of

probands with psychopathology unrelated to autism. [22]. In a similar study by

Constantino et al [26], the SRS was administered to 72 siblings, 48 siblings of ASD

probands and 24 siblings of non PDD psychiatric diagnoses.The mean SRS score for

siblings with PDD probands was substantially higher than that of siblings of child

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psychiatric patients without PDD in this study, confirming our findings that autistic

deficits measurable on the Social Responsiveness Scale aggregate in the siblings of

autistic probands[26].In our study, the total raw scores as well as the scores across all

sub-scales were lower than those reported in the above studies [22,26]. Non parametric

tests did not show statistically significant differences in scores generated using the two

versions of the questionnaire, namely Kannada and English (Table 10). Hence these

differences could have arisen due to socio-cultural factors influencing the perception of

the items being tapped in the questionnaire between Indian and Western populations. The

scales (social cognition and social mannerisms) which did not significantly differ in the

three groups showed lower scores than the other three groups, many scores being in the

range of zero to one, suggesting that they may need to be further adapted to the Indian

context.

Another confounding factor in our study was that 57.6% of the siblings studied were

female, with more females than males in the Autism sibling group and the Psychiatric

sibling group.As a lower phenotypic expression of genetic susceptibility of autistic traits

in the general population has been observed in girls, it is important to consider whether

this has affected the results [26]. In fact one could argue that the autistic traits, if

anything would have been more evident in male subjects, which would have only

increased the significance of the difference between this group and the others. Hence, this

does not definitely reduce our finding that the SRS discriminates siblings of autistics

from other groups. There were no significant differences in the SRS between the two

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sexes, in the group of siblings of autistic children as well as in the overall sample,

perhaps due to the unequal gender distribution in the sample, and smaller sample sizes.

Study limitations:

The limitations of our work were that no community norms are available in India for the

Childhood Autism Rating Scale (CARS), Strengths and Difficulties Questionnaire

(SDQ), Social Responsiveness Scale (SRS) and Autism Spectrum Quotient (ASQ) and it

is therefore difficult to assign cut offs. Assessment of the parents’ IQ and for the presence

of psychiatric illness was not done. Siblings were mostly girls in the autism and the

psychiatric control group. The sample size was small.

Conclusion

The results reported here indicate that milder deficits aggregate in the families of ASD

probands.Autism and the broader phenotype in autism represent the upper extreme of an

array of traits which are continuously distributed in nature.The universality of clustering

of autistic traits in close family members is suggested by this study, which shows that

internationally determined autistic traits discriminate families of autistic subjects in the

Indian context.Socio cultural factors in the interpretation of the two measures need to be

addressed before the differences between controls and cases can be interpreted with

certainty. The results of the study suggest that the two measures, namely the Social

Responsiveness Scale and the Autism Spectrum Quotient, used to identify broader autism

phenotype, have the potential to be employed in large genetic studies involving autism.

To use these measures in genetic studies, they have to be validated more stringently in

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unselected samples. This process may further their potential as readymade measures to

assess broader autism phenotype in the Indian context.

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Dr. Preeti Jacob, Senior Resident, Department of Child and Adolescent Psychiatry,

National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore.

Dr. M.V. Ashok, Professor, Department of Psychiatry, St. John’s Medical College

Hospital, Bangalore.