Behavioral Inhibition in Boys with Sex

Chromosome Aneuploidies

Marte Strandheim Wahlborg

Submitted as cand. psychol. thesis, Department of

Psychology, Faculty of Social Sciences

UNIVERSITY OF OSLO

October 2016

Behavioral Inhibition in Boys with Sex

Chromosome Aneuploidies

© Marte Strandheim Wahlborg

2016

Behavioral Inhibition in Boys with Sex Chromosome Aneuploidies

Marte Strandheim Wahlborg

http://www.duo.uio.no/

Abstract

Candidate: Marte Strandheim Wahlborg

Title: Behavioral Inhibition in Boys with Sex Chromosome Aneuploidies

Supervisor: Associate professor Krister Westlye Fjermestad

The current thesis is based on data from a research project at Frambu Resource Centre For

Rare Disorders, called “Psychosocial health in persons with Klinefelter syndrome”, as well as

data from the child section of the «Assessment and treatment – Anxiety in Children and

Adults (ATACA)» study conducted by Haukeland University Hospital. The work with this

thesis was commenced after data collection. Data for the Frambu project were collected in

2012 and data from the ATACA project were collected during 2008-2012.

Sex chromosome aneuploidies (SCA) are the most common chromosome irregularities, but

phenotypes vary greatly, and SCA are underdiagnosed. Boys with SCA represent an

understudied group. The temperament of boys with SCA has often been described in terms

such as shyness, withdrawal, low self-esteem, social isolation. Behavioral inhibition (BI) is a

temperamental trait that reflects a relatively consistent pattern of behavioral and emotional

responses to unfamiliar or novel situations. A temperament characterized by high BI involves

a tendency to react with fear, withdrawal, and cautiousness in the face of unfamiliar settings

or people. BI is suggested to be a significant predictor of later onset psychopathology,

particularly anxiety disorders. In the current thesis, BI is examined in a group of boys with

SCA. A sample of 25 Norwegian boys with SCA (mean age = 11.7 years, SD = 4.5) were

examined with the Behavioral Inhibition Questionnaire (BIQ). Parents rated their children on

the BIQ, which yield total scores and scores on six subscales. The scores of the SCA sample

were compared to the scores of a clinical sample comprised of boys referred to mental health

clinics for anxiety related problems, as well as to norms. The boys with SCA were scored as

high as the clinical sample on most aspects of BI, and were reported to be significantly more

inhibited in physical settings. Both the SCA and the clinical sample were overall scored

significantly higher than norms. Given that BI is considered an important predictor of later

onset anxiety, boys with SCA might have the same need for psychological assessment as

clinic-referred boys. This is currently not part of standard care.

Sammendrag

Kandidat: Marte Strandheim Wahlborg

Tittel: Behavioral Inhibition in Boys with Sex Chromosome Aneuploidies

Veileder: førsteamanuensis Krister Westlye Fjermestad

Hovedoppgaven bygger på data fra forskningsprosjektet “Psykososial helse blant personer

med Klinefelters syndrom”, gjennomført i regi av Frambu senter for sjeldne diagnoser, samt

data fra barnedelen av forskningsprosjektet “Assessment and treatment – Anxiety in Children

and Adults (ATACA)“ ved Haukeland universitetssykehus. Arbeidet med hovedoppgaven ble

gjort i etterkant av datainnsamlingen. Frambu-prosjektets data ble samlet inn i 2012, og

datainnsamling til ATACA-studien foregikk mellom 2008-2012

Kjønnskromosomavvik (sex chromosome aneuploidies, SCA) er den vanligste formen for

kromosomavvik. Det er stor variasjon i fenotyp, både mellom karyotyper og mellom

individer. Mange mennesker med SCA får aldri en diagnose, og gutter med SCA utgjør en lite

studert gruppe. Sosiale aspekter ved temperament hos gutter med SCA er i litteraturen

beskrevet med begreper som sjenerthet, tilbaketrukkenhet, dårlig selvtillit og sosial isolasjon.

Atferdsinhibisjon (behavioral inhibition, BI) er et temperamentstrekk som beskriver et relativt

stabilt mønster preget av emosjonelle og atferdsmessige responser på ukjente eller nye

situasjoner. Et temperament preget av høy grad av BI innebærer å reagere med frykt,

tilbaketrekning og forbeholdenhet i ukjente situasjoner eller med fremmede. BI antas å

signifikant predikere psykopatologi, og da særlig angsttilstander. Denne hovedoppgaven har

som mål å undersøke BI hos gutter med SCA. Ut utvalg bestående av 25 norske gutter med

SCA (gjennomsnittlig alder = 11.7 år, SD = 4.5) ble undersøkt med the Behavioral Inhibition

Questionnaire (BIQ). Foreldre skåret egne barn på BIQ, som gir totalskårer, samt skårer på

seks subskalaer: Skårene ble sammenlignet med skårene til et utvalg gutter som var henvist til

barne- og ungdomspsykiatriske klinikker (BUP) for angstrelaterte vansker, samt normskårer.

Guttene med SCA ble skåret like høyt som det kliniske utvalget på de fleste aspektene ved BI.

På domenet inhibisjon ved fysiske utfordringer, skåret guttene med SCA signifikant høyere.

Sammenlignet med normer, skåret SCA-utvalget og det kliniske utvalget generelt høyere på

BI. Med bakgrunn i at BI anses å være en viktig prediktor for senere angstlidelser, indikerer

resultatene at gutter med SCA kan ha et like stort behov for undersøkelse av eventuelle

psykologiske vansker som gutter henvist til BUP. Foreløpig er ikke dette del av standard

oppfølging for denne pasientgruppen.

Acknowledgements

This thesis uses data from a research project at Frambu Resource Centre For Rare Disorders,

called “Psychosocial health in persons with Klinefelter syndrome”, as well as data from the

child section of the «Assessment and treatment – Anxiety in Children and Adults (ATACA)»

study. I have been able to access data from these studies, and for this I am thankful. I would

also like to thank the families that participated.

My most sincere thanks goes to my supervisor, associate professor Krister Westlye

Fjermestad at the Department of Psychology at the University of Oslo. Not only have I

learned a lot from you, your fast-talking, no-nonsense and endlessly positive style goes right

home with me. Your knowledge, focus, and eye for detail has kept me on a steady course,

especially when I have found myself lost on sidetracks. You have been available to me, given

me feedback at the speed of light, and you made sure to check in at my progress when I was

lost. The fact that I’ve only cried in your office once, is proof of how safe and reassured your

competent guidance has made me feel in a time of general self-doubt and frustration. I am

grateful!

Anne-Marie Halberg provided some useful methodological insights and showed me how to do

analysis of variance from summary data – thank you!

My parents, Arve Strandheim and Kerstin Wahlborg, have been extremely supportive and

kept my morale up. They are my heroes, both highly competent health care professionals.

Both have provided important insights and helped proof-read this thesis. They have answered

my egocentric calls, tried to explain statistics, looked at houses for me, and most importantly,

sent me love and exchanged photos of puppies. I would also like to thank my brother Anders,

his girlfriend Ida and my amazing nephew Johan. It has been truly inspirational to watch him

learn how to walk, talk, and explore the world. My lovely family: thank you for your love,

advice, support and daily snapchats!

My lovely friend Marit read through this thesis and made insightful comments and

corrections. The fact that you took your time to help me while writing your own thesis, is

highly appreciated. Neither this thesis nor the six years of trying to become psychologists

would have been possible without you. I think we’ll make it now.

A big thanks goes to my fellow students, with whom I have shared instant coffee, frustrations,

laughs, and tears over the years. These last few months of sharing meals, discussing

italicization of abbreviations, and conducting our own study of emotion regulation strategies

(baby animals for the win) – it has been wonderful (in a painful kind of way).

And last, but certainly not least, I would also like to thank my friends. You have fed me,

housed me, entertained me, walked me, forced me to socialize, and listened to my frustrated

rants about life at the computer lab. I am so lucky to have smart, competent, empathetic and

solidly grounded friends who have encouraged me along the way. You know who you are,

and you are all priceless.

In the words of Albus Dumbledore: "Happiness can be found, even in the darkest of times, if

only one remembers to turn on the light." (Kloves, in screenplay based on Rowling, 1999). A

big thanks to everyone that helped me remember to turn on the light.

Marte Strandheim Wahlborg

Oslo/Blindern, October 2016

Index

1 Introduction ........................................................................................................................ 1

1.1 Sex chromosome aneuploidies .................................................................................... 1

1.1.1 Prevalence, diagnosis and etiology ...................................................................... 2

1.1.2 Endocrinology and physiology ............................................................................. 3

1.1.3 Psychological features .......................................................................................... 4

1.2 Temperament ............................................................................................................... 9

1.2.1 Behavioral inhibition .......................................................................................... 10

1.2.2 BI and physical activity ...................................................................................... 12

1.2.3 BI and related socio-emotional problems ........................................................... 12

1.3 Temperament and BI in boys with SCA .................................................................... 14

1.4 The current thesis ....................................................................................................... 16

2 Methods ............................................................................................................................ 18

2.1 Samples and procedures ............................................................................................ 18

2.1.1 SCA sample ........................................................................................................ 18

2.1.2 Clinical sample ................................................................................................... 19

2.1.3 Norms ................................................................................................................. 20

2.1.4 Research Ethics .................................................................................................. 20

2.2 Measures .................................................................................................................... 20

2.2.1 Reliability estimates ........................................................................................... 22

2.3 Data analysis .............................................................................................................. 22

3 Results .............................................................................................................................. 24

3.1 Differences between the SCA sample, clinical sample, and norms .......................... 24

4 Discussion ........................................................................................................................ 27

4.1 SCA, BI, and physical activity .................................................................................. 28

4.2 SCA, BI, and orientation towards adults ................................................................... 29

4.3 BI, social anxiety or problems with social functioning? ........................................... 30

4.4 The protective value of BI ......................................................................................... 31

4.5 Strengths and limitations ........................................................................................... 32

4.6 Ethics ......................................................................................................................... 35

4.7 Clinical implications .................................................................................................. 35

4.8 Research implications ................................................................................................ 36

5 Conclusions ...................................................................................................................... 38

References ................................................................................................................................ 39

Appendixes ............................................................................................................................... 53

Table 1. Description of participants ......................................................................................... 18

Table 4. T-test comparing the SCA sample to the clinical sample .......................................... 25

Figure 1. BIQ comparison scores. ............................................................................................ 26

Appendix 1. Cronbach’s alpha values for BIQ subcales .......................................................... 53

Appendix 2. BIQ total and subscale scores .............................................................................. 54

Appendix 3. Mean item BIQ total and subscale scores ............................................................ 55

Appendix 4. Effect sizes ........................................................................................................... 56

Appendix 5. Analysis of variance from summary data ............................................................ 57

1 Introduction

The temperamental style of boys with sex chromosome aneuploidies (SCA) is examined in

this thesis. Boys with SCA are often described as shy and withdrawn in terms of personality,

and increased socio-emotional problems have been documented for this group of children.

The temperamental trait behavioral inhibition (BI) can be measured with the Behavioral

Inhibition Questionnaire (BIQ), which yields scores on six situational domains. Behavioral

inhibition has been linked to socio-emotional difficulties and later onset anxiety. By scoring

the boys with SCA on the BIQ and comparing their scores to a sample comprised of boys

referred to community mental health clinics and norms, it is examined whether boys with

SCA have elevated scores on BI. The examination of temperamental traits in boys with SCA

represents a novel area of research on this group, and has potential implications for clinical

practice and further research.

Prevalence estimates and known etiologies of the karyotypes represented in this study, as well

as central endocrinological, physiological, and psychological aspects concerning boys with

SCA will be presented below. Aspects of BI that are expected to be relevant when studying

BI in boys with SCA are then briefly reviewed, before research questions examined in the

current thesis is presented.

1.1 Sex chromosome aneuploidies

Sex chromosomes determine whether an individual is born female or male. In humans, these

chromosomes are referred to as X and Y, and the sex chromosome pair comprises one of the

23 chromosome pairs. Most often, female individuals are born with two X chromosomes

(XX), and males with one X and one Y chromosome (XY). Aneuploidies (i.e., an atypical

number of chromosomes) are the most common chromosome abnormalities. In a review

article of the research on human aneuploidies, Hassold and Hunt (2001) estimated that

aneuploidies occur in approximately 5% of all pregnancies. Most fetuses with aneuploidies

are not viable, and the survival rate in utero is low (Hassold & Hunt, 2001). SCA refers to a

group of chromosome disorders characterized by individuals born with an atypical number of

sex chromosomes (Visootsak & Tartaglia, 2013). The current thesis examines a

heterogeneous group of male children with one of four sex chromosome karyotypes; 47,XXY,

47,XYY, 48,XXYY or 48,XXXY. These SCA conditions share some common features, but it

should be noted that there is a high degree of phenotype variability among individuals with

SCA, also within each karyotype.

1.1.1 Prevalence, diagnosis and etiology

With a prevalence rate estimated to be 1 in 400 births (Linden, Bender, & Robinson, 1995),

SCA are the most common chromosome aneuploidies in humans. The most common SCA

conditions are Turner syndrome in females (45,X) and Klinefelter syndrome (KS) (47,XXY)

in males.

Prevalence rates of SCA conditions are based on larger screening studies, where cohorts of

newborns are genetically tested. Due to the fact that genetic testing is not part of standard

newborn screening practice, SCA conditions are heavily underdiagnosed. When comparing

the number of individuals clinically detected and the prevalence rates, only an estimated 25%

of all individuals with SCA will get diagnosed in their lifetime, and many are not diagnosed

before adolescence or early adulthood years (Visootsak & Tartaglia, 2013). Prevalence

estimates and etiology for each karyotype are presented below.

47,XXY

Klinefelter syndrome, 47,XXY, has an estimated prevalence between 1 in 426 to 1 in 1000

male individuals (Bojesen, Juul, & Gravholt, 2003; Cordeiro, Tartaglia, Roeltgen, & Ross,

2012; Gravholt, 2013). The addition of an extra X chromosome happens in early phases of

embryonic cell divisions. The extra X chromosome can have either a maternal or paternal

origin, each answering for approximately half of the cases. Increased parental age is

associated with the addition of the extra X chromosome in KS (Lorda-Sanchez, Binkert,

Maechler, Robinson, & Schinzel, 1992).

47,XYY

Karyotype 47,XYY, sometimes referred to as XYY syndrome or Jacobs’ syndrome, has an

estimated prevalence of 1 in 1000 male births, and 90% of individuals with 47,XYY will

never get the diagnosis in their lifetime (Gravholt, 2013; Ross et al., 2012). XYY syndrome

occurs because a sex chromosome fails to divide. This can either happen when a sperm cell

with a non-divided YY chromosome fertilizes an egg with a X chromosome, or after the

zygote has been formed (Visootsak & Tartaglia, 2013). The extra Y chromosome is always

paternal in origin (Gravholt, 2013).

48,XXYY

A less common aneuploidy, 48,XXYY has an estimated prevalence of 1 in 18 000 to 1 in 40

000 male births (Sorensen et al., 1978, in Tartaglia, Ayari, Howell, D’Epagnier, & Zeitler,

2011). It is the only SCA with both supernumerary X and Y chromosomes, and it is argued

that this karyotype is likely to have a paternal origin (Hanley et al., 2015).

48,XXXY

Karyotype 48,XXXY has an estimated prevalence of 1 in 50 000 male births. Less is known

about what causes this aneuploidy. It is suggested that nondisjunction (i.e., the failure of

proper division of maternal and paternal chromosomes, resulting in uneven numbers of

chromosomes) either in paternal sperm or maternal ovarian cells causes this karyotype

(Tartaglia et al., 2011).

1.1.2 Endocrinology and physiology

For the conditions with supernumerary X chromosomes (47,XXY, 48,XXYY and 48,XXXY),

hypogonadism and low testosterone levels are prevalent, and estimated to be found in 65-85%

of all post-pubertal men with 47,XXY (Smyth & Bremner, 1998). Males with karyotype

47,XYY usually have normal testosterone levels (Cordeiro et al., 2012; Gravholt, 2013).

Typically, hypogonadism in these individuals is hypergonadotropic, meaning that the

individuals have a primary impaired response to hormonal secretion causing low production

of testosterone in utero and throughout life (Aksglæde, Skakkebæk, Almstrup, & Juul, 2011;

Cordeiro et al., 2012; Høst, Skakkebæk, Groth, & Bojesen, 2014; Visootsak & Tartaglia,

2013). Hypergonadotropic hypogonadism often causes low testicular volume and/or penile

size and high rates of infertility, as well as sparse body hair growth. Gynecomastia (i.e., male

breast development) has a tentative frequency of up to 75% among men with karyotype

47,XXY (Groth, Skakkebæk, Høst, Gravholt, & Bojesen, 2013). High levels of the follicle-

stimulating hormone (FSH) and luteinizing hormone (LH) as a compensatory effect, is not

uncommon (Høst et al., 2014). In addition to regulating sperm production, estrogen and

testosterone secretion (Hauge, 2014), FSH and LH are involved in growth regulation, and this

may partly be the reason why individuals with 47,XXY are tall in stature with long limbs.

When 305 persons with SCA from patient centers in Denmark and the US were studied, the

main finding was that height increased with an increasing number of extra X or Y

chromosomes, with some exceptions (e.g., males with five and females with four or five sex

chromosomes) (Ottesen et al., 2010). It is also hypothesized that increased height may be due

to supernumerary copies of height-determining genes. For individuals with extra X

chromosomes, bone epiphysis (i.e., the closure of bone growth) is often delayed due to

decreased testosterone levels, and this may also prolong the growth process.

High rates of scoliosis (i.e., deviations of the backbone), clinodactyly (i.e., curved finger

bones), and loose ligaments are often found in males with SCA. As facial dysmorphology is

not common, there is no recognizable set of facial features common for males with SCA,

probably contributing to SCA conditions being underdiagnosed (Ross et al., 2008; Visootsak

& Graham, 2006).

1.1.3 Psychological features

Klinefelter, Reifenstein, and Albright (1942) reported 9 cases in the original article describing

the disorder later known as Klinefelter syndrome. The main focus of the article was to

describe endocrine features, and descriptions of psychological functioning were limited to

terms such as “Examination showed a rather obese, unintelligent, timid, self-conscious man

…”(p. 624),“…a 28-year-old feebleminded white houseboy…”(p. 624), “…a tall, immature

boy…”(Klinefelter et al., 1942, p. 625). Individuals with SCA conditions were described as

having deviant behaviors, low IQ, and a high prevalence of psychiatric disorders. Klinefelter

et al.’s (1942) descriptions are products of their time, and early research is today considered

biased and flawed with methodological errors. Newer research on the cognitive, social and

behavioral functioning of individuals with SCA has shown that this group is highly

heterogeneous (Götz, Johnstone, & Ratcliffe, 1999; Leggett, Jacobs, Nation, Scerif, &

Bishop, 2010; Samango-Sprouse, 2001; Visootsak & Graham, 2006).

Cognitive functioning

Early reports of intelligence in SCA samples have later been criticized for being biased, as

many samples were recruited from correctional facilities and institutions for individuals with

learning disabilities and psychiatric disorders. Most studies also had small sample sizes. A

more recent systematic review from the UK aimed to examine the literature on neurocognitive

outcomes among individuals with sex chromosome trisomy (Leggett et al., 2010). Data from

702 studies from 50 years of research across several countries (mainly the US and Europe)

were reviewed, and major ascertainment bias ( i.e., using a non-random sample), was the

cause of exclusion for 64 of the studies. The main finding was that mean IQ scores of

individuals with sex chromosome trisomies were within normal limits (Leggett et al., 2010).

An American study examined intelligence in 174 boys with SCA aged 4 to 18 years (Cordeiro

et al., 2012). The study included 40 boys with karyotype 47,XYY, 102 boys with karyotype

47,XXY and 32 boys with karyotype 48,XXYY. Wechsler test results were obtained from

86% of the participants. Among boys with 47,XXY the full scale IQ ranged from 46-141 with

a mean score of 98, indicating cognitive abilities within the normal range. Among boys with

karyotype 47,XYY, the full scale IQ ranged between 56-127, with a mean score of 92.

Among boys with karyotype 48,XXYY, IQ scores ranged between 48-102, with a mean score

of 79 (Cordeiro et al., 2012). Thus, tetrasomy conditions (karyotypes 48,XXYY and

48,XXXY) have larger impact on IQ than trisomy conditions (47,XXY and 47,XYY)

(Gravholt, 2013; Linden et al., 1995; Tartaglia et al., 2011; Visootsak, Rosner, Dykens,

Tartaglia, & Graham, 2007; Visootsak & Tartaglia, 2013). Significantly lower mean verbal IQ

scores than mean performance IQ scores has been found across all karyotypes. In a Canadian

longitudinal study, 35 boys with SCA were studied from childhood to adolescence (Rovet,

Netley, Bailey, Keenan, & Stewart, 1995). Children with supernumerary X chromosomes

were found to score significantly lower than controls on Wechsler verbal IQ subtests,

including verbal comprehension. Skewedness in IQ profiles was also found in an American

study when the language skills of 14 boys with SCA aged 5 to 12 years were examined.

Results were compared to those of a control group (Graham, Bashir, Stark, Silbert, & Walzer,

1988). For the SCA sample, IQ scores in verbal domains were lowered, compared to

performance domains. The SCA sample showed significant impairments in expressive

language, while verbal comprehension was less affected. Based on these findings, Graham et

al. (1988) hypothesized that low scores on verbal IQ can be seen as delay of expressive

language, due to problems with motor imitation and low number of vocalizations.

In summary, full scale IQ scores are generally within the normal range for boys with

karyotypes 47,XXY and 47,XYY. For the tetrasomy conditions, full scale IQ scores are often

lowered. For all karyotypes, the tendency is that verbal IQ scores are lower than performance

IQ scores.

Social phenotypes

Based on the medical records of 104 adult American patients with 47,XXY, Becker (1972)

summarized clinical and therapeutic experiences and noted that “..although many different

personalities were found, frequently noted characteristics included timidity, a withdrawn and

introspective behavior, a lack of physical and social drive….” (Becker, 1972, p. 568)”. In a

Scottish population screening study, 12 boys aged 15 to 17 years, were identified with

karyotype 47,XXY (Bancroft, Axworthy, & Ratcliffe, 1982). The boys were interviewed with

The High School Personality Questionnaire, and compared to controls. When interviewed

about their personalities, common themes in the 47,XXY group was timidity, lack of

assertiveness, being less confident, and having problems relating to the peer group (Bancroft

et al., 1982).

In a more recent American study, 108 boys with SCA aged 4 to 15 years were compared to

controls on several measures of psychological and behavioral functioning (Ross et al., 2012).

Two karyotypes were represented, 26 boys with karyotype 47, XYY and 82 boys with

karyotype 47,XXY. Parents rated their children on the Conners’ Parent-Rating Scale

(Conners, Sitarenios, Parker, & Epstein, 1998), and Ross et al. (2012) found that both SCA

groups were rated significantly more anxious-shy than controls.

In an American study of 174 boys with SCA aged 4 to 18 years, social functioning was

studied (Cordeiro et al., 2012). Three karyotypes were represented; 40 boys with karyotype

47,XYY, 102 boys with karyotype 47,XXY, and 32 boys with karyotype 48,XXYY. Social

functioning was measured using the Social Responsiveness Scale (SRS). The SRS measures

levels of autism spectrum symptoms in several domains. When the SCA subgroups were

compared, Cordeiro et al. (2012) found that boys with karyotypes 47,XYY and 48,XXYY had

scores in the severe range. The boys with karyotype 47,XYY and 48,XXYY scored higher

than boys with karyotype 47,XXY on traits associated with autism spectrum disorder (ASD),

such as shyness, social difficulties, and social withdrawal. Severe difficulties was found for

20% of the boys with karyotype 47,XXY, 50% of the boys with 47,XYY and 44% of the boys

with karyotype 48,XXYY, compared to 7% of the normative sample comprised of 512 boys.

Problems with social responsiveness were elevated for boys in the SCA groups, even for boys

with no previous ASD diagnosis. This suggests that the extra Y chromosome may contribute

to social deficits and ASD symptomatology (Cordeiro et al. (2012). Elevated ASD symptoms

are more commonly found among 47,XYY individuals than among the boys with karyotype

47,XXY, suggesting that the ASD-related behaviors are somehow related to Y-specific genes

(Cordeiro et al., 2012; Ross et al., 2012).

In summary, the social functioning of boys with SCA is characterized by shyness, withdrawal,

and anxiousness. Difficulties with social responsiveness have been found across karyotypes.

Socio-emotional problems in boys with SCA

Aiming to determine the prevalence of depressive symptoms in adolescents and adults with

SCA, Turriff, Levy, and Biesecker (2011) studied 310 boys and men aged 14 to 75 years

(mean age = 40.7 years). Participants were recruited from regional and national support

networks in both the UK and the US, and all participants were diagnosed with karyotype

47,XXY. Participants completed a web-based survey, and answered questions about

depression, perceived stigmatization, and coping style. The majority of the participants

reported clinically significant levels of depression. Perceptions of stigmatization and focusing

on negative aspects of the SCA diagnosis were associated with depressive symptoms. Due to

the endocrine features of SCA infertility is common, and thinking about the importance of

having children was linked to depressive symptoms in this sample. A coping style categorized

by emotion-focused coping strategies (e.g., avoidance, wishful thinking, and self-blame) was

also significantly associated with depression. However, in an American study of 108 boys

with SCA (karyotypes 47,XXY and 47,XYY) Ross et al. (2012) did not find increased risk of

self-reported anxiety or depression in boys with SCA. The study included 26 boys with

karyotype 47, XYY, 82 boys with karyotype 47,XXY, and behavioral problems were also

examined. Parents rated their children on the Child Behavior Checklist (CBCL; Achenbach,

2009) and most boys with SCA were rated within the normal range. However, a

predisposition to behavioral problems for some boys with 47,XYY was found. When

compared to the 47,XXY sample, problem behaviors were rated significantly higher for the

boys with karyotype 47,XYY (Ross et al., 2012).

Symptoms associated with attention-deficit hyperactivity disorder (ADHD) were studied in

142 American boys with SCA aged 5 to 20 years (Tartaglia, Ayari, Hutaff-Lee, & Boada,

2012). 56 boys with karyotype 47,XXY, 33 boys with karyotype 47,XYY, and 53 boys with

karyotype 48,XXYY were assessed by a developmental-behavioral pediatrician and ADHD

symptoms were rated by parents on the Conners’ Parent Rating Scale. 36% of the boys with

karyotype 47,XXY, 76% of the boys with karyotype 47,XYY, and 72% of the boys with

karyotype 48,XXYY had scores in the ADHD range. Treatment with stimulants was found to

be effective, and it was recommended that since children with SCA seems to be at increased

risk for ADHD symptoms, ADHD evaluation and treatment should be considered (Tartaglia

et al., 2012).

Karyotype 47,XYY gained public interest in the 1960s and 1970s. This was due to the

examination of severe problem behaviors among men with 47,XYY, aiming to study the

origins of criminal behavior. The men examined were recruited from mental health

institutions and correctional facilities, and karyotype 47,XYY was linked with criminal

convictions and antisocial behavior (see Casey et al., 1972; Casey, Segall, Street, & Blank,

1966; Jacobs, Brunton, Melville, Brittain, & McClemont, 1965; Jacobs, Price, Brown,

Brittain, & Whatmore, 1968). These studies have been criticized for methodological caveats,

such as the fact that SCA participants were preselected for antisocial behavior and recruited

from special settings (e.g., institutions for persons with learning disabilities, mental health

institutions, and/or correctional facilities) (Götz et al., 1999). More recent studies of

behavioral problems in boys with SCA tend to only find a weak predisposition for behavioral

problems. Using a population-based sample of UK men with SCA, Götz et al. (1999) studied

frequency of antisocial personality disorder in men with SCA aged 18 to 26 years. A group of

17 men with karyotype 47,XYY, and 17 men with karyotype 47,XXY were compared to

controls. Rates of criminal convictions were examined, and males with karyotype 47,XYY

were found to have higher frequency of antisocial behaviors and criminal convictions than

controls. However, multiple regression analysis showed that this was mediated mainly

through lowered intelligence. It has been suggested that the extra Y chromosome might lead

to a slightly increased risk of criminal behaviors in some individuals, mediated by cognitive

characteristics combined with environmental factors such as dysfunctional families and low

social support (Gravholt, 2013).

Individuals with karyotype 48,XXYY have sometimes been described as aggressive, and

often score clinically significant on aggression, depression, conduct problems, and

hyperactivity, whereas 48,XXXY individuals’ behavior is typically described as passive, not

aggressive and more cooperative (Visootsak & Graham, 2006; Visootsak et al., 2007). In an

American study, Visootsak, Rosner, Dykens, Tartaglia, and Graham (2006) compared 11

adult men (mean age = 21 years) with karyotype 48,XXYY, to a group comprised of 13 males

with karyotypes 48,XXXY and 49,XXXXY. Participants and their families completed the

Vineland Adaptive Behavioral Scales, CBCL and Reiss Personality Profiles. Both

internalizing and externalizing behaviors were more frequent in males with karyotype

48,XXYY, and this group showed elevated scores on domains such as anxiety, frustration and

vengeance. Visootsak et al. (2006) pointed out that both groups had communicative problems

that may result in maladaptive behaviors. A sample of 53 adult Norwegian men with SCA

aged 19 to 67, answered a survey of self-reported education, work and health (Stokke,

Fjermestad, & Bahr, 2015). Compared to the general population in Norway, the men had less

years of post high-school education, and only 38% reported to be working. 57% experienced

learning difficulties, significantly associated with lower education. Almost 40% reported

experiencing misunderstanding in conversations and 35% reported having problems with

understanding the contents of conversations. In addition, 24% reported experiencing anger.

Having communicative problems with frequent misunderstandings influences behavior, social

functioning, and participation in school and work. Based on these findings, the authors

concluded that knowledge of these challenges is important information for education and

health care professionals (Stokke et al., 2015).

1.2 Temperament

Human individuals react and interact with their social and physical environments in their own

distinct ways as soon as they are born. Temperament can be defined as individual differences

in reactivity and self-regulation, and is assumed to be biologically based (Rothbart &

Derryberry, 1981). The term temperament is used to describe a general style of reacting

emotionally and behaviorally to the environment, and refers to individual differences in

emotion, motor activation, and attentional reaction when facing stimuli (Rothbart & Gartstein,

2008). Temperament includes the aspects of personality that are considered to be innate,

present from early infancy, and a foundation for development of various psychological

outcomes (Bishop, Spence, & McDonald, 2003; Kagan & Snidman, 1991; Tetzchner, 2012).

In a review of 152 longitudinal studies of temperament and personality, Roberts and

DelVecchio (2000) summarized the evidence for the consistency of temperament and found

that temperament constructs ranges from relatively low to moderate levels of consistency

across infancy and childhood. They find that stability increases with age, and that adult

personality is a more stable construct than temperament (Roberts & DelVecchio, 2000).

1.2.1 Behavioral inhibition

The term behavioral inhibition (BI) was described by Kagan, Reznick, Clarke, Snidman, and

Garcia-Coll (1984), and refers to a pattern of behavioral and emotional responses, especially

to new and unfamiliar situations, people, objects or places. Jerome Kagan’s contributions to

research on temperament include studies of the tendency to be more or less inhibited and

temperamental aspects of fear and surgency (i.e., the personal attribute of dominance, self-

confidence, being outgoing and competitive; Rothbart & Gartstein, 2008). In Kagan and

colleagues’ 1984 original articles (Garcia Coll, Kagan, & Reznick, 1984; Kagan et al., 1984),

data from American toddlers aged 21 and 31 months old were used. The 305 participants were

recruited by letters or phone calls to parents of infants born in Boston hospitals. Parents were

interviewed about their children, and inhibited and uninhibited children were identified in the

samples. A total of 60 inhibited and 60 uninhibited children were selected, and participated in

laboratory procedures where the children’s reactions to six various events (including warming

up to the laboratory setting, playing, modeling with toys, being exposed to unfamiliar adults

and unfamiliar toys, and being separated from caregivers) were observed and coded. Two

distinctly different reactions to such events were observed in the laboratory. The inhibited

children became quiet and stopped the activity they were engaged in, withdrew from the

unfamiliarity or sought out support from a familiar and safe person. The uninhibited children

showed no marked changes in behavior, and some even approached the unfamiliar stimuli

(Kagan et al., 1984).

The difference in these patterns of reactions; a tendency towards either being inhibited or

uninhibited, was also reflected in physiological measures (e.g., heart rate, pupillary dilation,

muscle tension, norepinephrine and cortisol levels; Kagan, Reznick, & Snidman, 1987). The

children included in the original study were categorized into two cohorts; inhibited or

uninhibited, and were included in a longitudinal study. The cohorts were followed until the

age of 7.5 years. The children categorized as inhibited exhibited signs of greater physiological

arousal than their uninhibited peers when exposed to novel situations. Thus, Kagan et al.

(1987) hypothesized that there might be differences in hypothalamic-pituitary-adrenal axis

(HPA) activation, reticular activation system (RAS) and activation of the sympathetic branch

of the autonomic nervous system, and that responsivity in these structures has a lower

threshold in inhibited children. Kagan and Snidman (1991) studied 94 American children at

ages 2, 4, 9, 14 and 21 months in laboratory settings. The children were observed in the

presence of their mothers, as they looked at objects and listened to a tape of a female voice

speaking nonsense syllables. Based on their reaction patterns, the children were classified as

either “high motor activity and high crying” (23%), “low motor activity and low crying”

(37%), “low motor activity and high crying” (22%) or “high motor activity and low crying”

(18%) at 4 months of age. “High motor activity and high crying” or “low motor activity and

low crying” at 4 months of age predicted a disposition to either avoid or approach unfamiliar

events at 21 months of age. The authors argued that these displays of distinctive patterns

reflect differences in the limbic system, and that the amygdala might have a lower threshold

for stress activation in inhibited children (Kagan et al., 1987; Kagan & Snidman, 1991;

Nachmias, Gunnar, Mangelsdorf, Parritz, & Buss, 1996). However, the findings are not

conclusive, and Gunnar, Larson, Hertsgaard, Harris, and Brodersen (1992) argued that

increases in cortisol could be due to separation and distress, not fear of novelty. They studied

distress in 9 month old American infants in separation situations. A sample of 38 infants

(mean age = 9.1 months) were placed in a novel setting and separated from their primary

caregiver for 30 minutes, and the infants were left with a substitute caregiver that was

relatively non-interactive and busy. This yielded significant adrenocortical responses. When

the substitute caregiver’s behavior was altered to being warmer and more responsive, negative

affect and adrenocortical responses were significantly lowered. Gunnar et al. (1992) argued

that temperament may not be the only relevant individual difference that mediate stress

reactions. Quality of attachment, previous experiences with separation and interaction effects

of these variables might impact how infants adjust to separation and novelty situations.

Longitudinal studies of the children from Kagan et al.’s studies allowed measurement of

stability. Both Kagan et al. (1987) and Hirshfeld et al. (1992) assessed the stability of BI

across time. BI was assessed at 21 months, 4, 5 and 7 years of age. At age 7 years, 70% of the

original samples participated. Although a small portion of the children seemed to change the

degree of inhibition, the main conclusion was that BI can be considered a “moderately stable”

trait. Degnan and Fox (2007) reviewed several longitudinal studies of continuity and

discontinuity. Overall, the studies have found that inhibited toddlers are likely to also be

inhibited at later ages.

The question of whether BI represents continuous quantities or discrete qualities of behavior,

was raised by Kagan et al. (1987), and it is still discussed whether BI is a categorical

construct with patterns of behaviors or a continuum of behavioral features. Bishop et al.

(2003) argued that measuring and assessing behaviors related to BI is of importance when

trying to study and understand these features in children (Bishop et al., 2003). Ecological

validity has also been debated, and it is worth noticing that the construct BI was

operationalized under laboratory settings and demand conditions (Hayward, Killen, Kraemer,

& Taylor, 1998; Kagan, Reznick, & Snidman, 1988).

1.2.2 BI and physical activity

An important aspect of BI is how the child handles settings involving physical challenges.

The degree of BI affects aspects of cautiousness or confidence in play activities that involve

physical challenges, and being hesitant or happy when exploring new toys and equipment

(Bishop et al., 2003). In a review of the literature on developmental aspects of physical

activity play, Pellegrini and Smith (1998) found both age and sex differences. Generally,

physical activity in play begins in early infancy, peaks in childhood, and declines in

adolescence. Sex differences in motor activity levels seem to be age specific, and there is no

evidence for sex differences under 12 months of age (Eaton & Enns, 1986). In a meta-analysis

of 90 studies of sex differences, Eaton and Enns (1986) found significant differences in motor

activity level in play, where boys generally are more active than girls from late infancy and

well into adolescence. This pattern can also be seen in other mammals, and thus it is

hypothesized that biological factors such as hormonal influences might play an important role

in sex differences. Parents normally engage in more physical play with boys than with girls,

and Meaney, Stewart, and Beatty (1985) argued that from early interactions with parents,

boys and girls are socialized into different ways of playing. It is hypothesized that this might

reinforce differences between the sexes in motor activity levels. Social expectations that boys

should be more assertive, active, physical, and willing to take risks than girls, might suggest

that an inhibited temperamental style may be more problematic for boys than for girls.

1.2.3 BI and related socio-emotional problems

The pattern of social withdrawal, negative affect, and low self-esteem associated with BI is

argued to impact children’s psychosocial development, including the development of certain

psychopathological conditions (Rosenbaum et al., 1988). Evidence of the relationship

between BI and both internalizing and externalizing behaviors has found. When reviewing 20

years of literature on BI, Fox, Henderson, Marshall, Nichols, and Ghera (2005) pointed out

that an important area for future research lies in expanding knowledge about the possible

mechanisms of BI in the etiology of psychopathology. It has been suggested that since

inhibited children are less confident and assertive, they might experience more social

rejection, and also have a tendency to interpret ambiguous social situations as rejections (Fox

& Pine, 2012; Schwartz, Snidman, & Kagan, 1999). Another hypothesis proposes that a high

degree of experienced social rejection could lead to an internalization of rejection, in time

enforcing further social avoidance (Rubin, 1993; Rubin, Chen, McDougall, Bowker, &

McKinnon, 2009). In interaction with other children, inhibited children are less assertive and

confident, thus more prone to experiencing rejection (Fox & Pine, 2012), and it is

hypothesized that inhibited children may experience fewer opportunities to interact with

peers, thus development of social competence may be disturbed (Garcia Coll et al., 1984;

Kagan et al., 1984; Rubin, Both, & Wilkinson, 1990).

In a meta-analytic study of BI and the risk of developing social anxiety disorder, Clauss and

Blackford (2012) reviewed 85 articles, and found that an estimated 15 - 20% of all healthy

children can be categorized as having a high degree of BI (Kagan & Snidman, 1999). Of these

children with a high degree of BI, 43% developed social anxiety, and the authors concluded

that BI is one of the largest single risk factors for developing social anxiety disorder (Clauss

& Blackford, 2012). Another finding linking BI and anxiety disorders, was Hirshfeld et al.’s

(1992) examination of data from children found to be consistently inhibited at age 21 months,

4, 5.5, and 7 ½ years in the longitudinal studies of the children from Kagan et al.’s studies

(Garcia Coll et al., 1984; Kagan et al., 1984). The stable inhibited children were compared to

those who were not consistently inhibited, and the children with a stable degree of BI were

found to have a higher prevalence of multiple anxiety disorders and phobias. Reports of stable

inhibition and anxiety was found when Schwartz et al. (1999) studied 79 American 13-year-

olds who had been classified as inhibited at age 2 years. The sample was comprised of

children who had participated in the Kagan et al. studies (Garcia Coll et al., 1984; Kagan et

al., 1984). With a hypothesis that social anxiety would be prevalent among the adolescents

who had been classified as inhibited at age 2 years, the sample was interviewed with a semi

structured interview based on the Diagnostic Interview Schedule for Children (Shaffer et al.,

1996). The results indicate that aspects of inhibition were preserved into adolescence, and

suggest an association between BI as a toddler and social anxiety as a teenager, with

significant association only for generalized social anxiety and not for specific fear,

performance or separation anxiety.

Studying 2242 American high school students (mean age = 15.1 years) over a period of 4

years, Hayward et al. (1998) also examined anxiety and inhibition. BI was assessed with The

Retrospective Self-Report of Inhibition (Reznick, Hegeman, Kaufman, Woods, & Jacobs,

1992), and anxiety with The Social Phobia and Anxiety Inventory (Turner, Stanley, Beidel, &

Bond, 1989), as well as a structured clinical interview that assessed anxiety and depression. It

was demonstrated that childhood BI predicts onset of social phobia later in life, in accordance

with the findings presented above. However, one dimension of childhood BI was also linked

with comorbid depression. Presence of the fearfulness component of BI increased the risk of

both social phobia and depression, whereas the social avoidance component only increased

the risk of social phobia. In a study of 778 Canadian boys aged 10 to 15 years, Kerr,

Tremblay, Pagani, and Vitaro (1997) compared behavioral profiles of boys aged 10-12 years

to outcome profiles of boys aged 13-15 years. The sample comprised boys from low socio-

economic status areas, and explored how inhibition and disruptive behavior interact. The

findings indicated that inhibition might increase the risk of later depressive symptoms, and

that boys with a pattern of disruptive and withdrawn behavior were found to be more likely to

develop depressive symptoms (Kerr et al., 1997).

1.3 Temperament and BI in boys with SCA

Most studies of early temperament have examined normally developing children, as is the

case for most studies on BI. Early studies of children with developmental delays linked

“difficult temperaments” with behavioral problems (see Thomas & Chess, 1977). Measuring

methods created for normally developing children applied in samples of children with

developmental delays, has been debated (Crnic, Hoffman, Gaze, & Edelbrock, 2004;

Marcovitch, Goldberg, Lojkasek, & MacGregor, 1987). However, it has been argued that

insight in temperamental aspects may be valueable information for parents that care for and

interact with children with developmental delays (Crnic et al., 2004; Marcovitch et al., 1987).

In more recent years, the number of studies examining temperament in children with various

developmental challenges have increased. For instance, the temperament of children with

Down syndrome has been studied and compared with the temperament of controls. In these

studies, temperament has been measured on various traits and temperamental dimensions,

thus findings are mixed. Generally, temperamental differences between children with Down

syndrome and controls are rather small, with a high degree of variability between individuals

(see Bridges & Cicchetti, 1982; Gunn & Cuskelly, 1991; Nygaard, Smith, & Torgersen, 2002

for examples.). As additional examples, some studies have examined temperament in children

with low birth weight compared to normally developing children. A sample of 62 American

preterm infants at ages 3 and 7 months, were measured on stability of temperament, including

aspects of inhibition (Garcia Coll, Halpern, Vohr, Seifer, & Oh, 1992). The preterm infants

were compared to full-term peers. All children were less inhibited with time (at 7 months,

compared to 3 months old), but an interaction effect with time and days on ventilation, was

significant; the preterm infants that required more days with respiratory aid and ventilation at

hospital, were more inhibited at 7 months old, than those with fewer days on ventilation

(Garcia Coll et al., 1992).

Some studies have examined aspects of temperament in children with SCA. Boys with SCA

have generally been described as more timid, less confident and having more problems

relating to peers than controls (Bancroft et al., 1982; Bender, Harmon, Linden, & Robinson,

1995; Cordeiro et al., 2012). Similar descriptions are frequently used for children with a high

degree of BI (Hirshfeld et al., 1992; Kagan et al., 1984; Kagan et al., 1987; Kagan, Reznick,

Snidman, Gibbons, & Johnson, 1988; Schwartz et al., 1999).

Studying 108 American boys with SCA aged 4 to 15 years, a temperamental style close to BI

was described by Ross et al. (2012). BI- related behaviors like withdrawal and shyness are

represented in the Conner’s Parent Rating Scale and the parents of boys with 47,XXY and

47,XYY rated their sons significantly more anxious-shy than the parents in the control groups

rated their sons. Boys with 47,XXY were significantly more withdrawn than controls, and

boys with 47,XYY significantly more withdrawn than both controls and boys with 47,XXY.

Further evidence of social withdrawal in SCA individuals was found when Cordeiro et al.

(2012) compared 102 boys with 47,XXY, 40 boys with 47,XYY, 32 boys with 48,XXYY, and

a normative sample of 512 boys. Severe difficulties in social responsiveness were found in

19.6% of the boys with 47.XXY, 50.0% of the boys with 47,XYY and 43.8% of the boys with

48,XXYY, compared to 7.4% of the boys in the normative sample.

1.4 The current thesis

The current thesis aims to examine BI in a group of boys with SCA. The data used were

collected as part of a study of persons with SCA conducted at Frambu, a national competence

centre for rare genetic disorders in Norway. The centre provides services to individuals,

families and professionals for approximately 130 rare disorders, among them SCA. The

Frambu research project “Psychosocial health in persons with Klinefelter syndrome” was

conducted in 2012, and sought out more knowledge about the quality of life and psychosocial

health of boys and men with Klinefelter syndrome and other SCA conditions. Fjermestad et

al. (2015) reported socio-emotional problems in the boys with SCA recruited in the Frambu

study. Boys with SCA were found to have as severe socio-emotional problems as boys

referred to mental health services for anxiety symptoms, but almost none received treatment.

The SCA sample was assessed with the Strengths and Difficulties Questionnaire (SDQ;

Goodman, Ford, Simmons, Gatward, & Meltzer, 2000). In Fjermestad’s (2015) study there

were only small effect sizes between the SCA sample and the clinical sample, but medium to

large effect sizes on all SDQ subscales when comparing the SCA sample to a norm group,

leading to the conclusion that boys with SCA may have the same need for psychological

assessment and interventions as the boys referred to community child and adolescent mental

health clinics.

The clinical sample used for comparison in the current thesis, is comprised of participants

from the Norwegian study “Assessment and Treatment - Anxiety in Children and Adults”

(ATACA), a randomized control study conducted in Western Norway in 2008 to 2012

("Effectiveness Study of CBT for Anxiety in Children (ATACA)" 2013).

These findings suggest that boys with SCA might score high on some of the aspects that

comprise BI, due to their general level of socio-emotional problems. However, the degree of

BI in boys with SCA has not been established. Knowledge of physical, cognitive, social,

temperamental and psychological characteristics of boys with SCA is still limited. Research

on a wide array of characteristics might be useful in creating clinical guidelines for when

SCA should be suspected, tested for, and how it should be treated in the health services. The

current thesis aims to contribute to this knowledge by examining the temperamental style of

BI among boys with SCA, compared to a clinical sample of boys referred to community

mental health services, and to norm data.

The current thesis addresses the following research questions: (1) Are boys with SCA

behaviorally inhibited?; (2) To what degree do boys with SCA display BI, and in which

domains?; (3) Do boys with SCA have elevated scores on BI compared to (a) a clinical

sample and (b) norms?; (4) In which domains of BI do the SCA sample and clinical sample

have similar scores, and in which domains do they differ? Based on descriptions of typical

temperamental styles of boys with SCA, it is expected that these boys will also have elevated

scores on BI when compared to norms. The clinical sample represents referrals to community

mental health clinics, and it is therefore expected that the clinical sample will have elevated

scores. Thus, it is expected that boys with SCA and clinically referred boys will obtain similar

BI scores, and that both these groups will have elevated BI scores relative to norms.

2 Methods

2.1 Samples and procedures

2.1.1 SCA sample

The SCA sample consists of 25 boys with four different karyotypes. 47,XXY constitutes the

largest subgroup. The sample also includes boys with karyotypes 47,XYY, 48,XXYY and

48,XXXY. The mean age for the SCA sample was 11.7 years (SD = 4.5, range 2 -18 years).

See Table 1 for means, standard deviations and range of age of the participants of each

karyotype.

Table 1. Description of participants

47,XXY

(N = 13)

47,XYY

(N = 6)

48,XXYY

(N = 3)

48,XXXY

(N = 3)

Age (years)

M (SD) 12.4 (4.5) 13.0 (3.2) 9.3 (5.5) 8.3 (5.7)

Range 4-18 8-17 3-13 2-13

Socioeconomic status (SES) was estimated in accordance with guidelines from the Registrar

General Social Class coding scheme, classifying parent occupational status into five rank

ordered socio-economic status classes (Currie et al., 2008). For the SCA sample, 36% of

families were categorized as high SES, 32% as medium, and 32% as low.

The participants were recruited from two different settings. The database at Frambu was used

to recruit 18 of the participants. Families can self-refer and registration in the user database is

voluntary. At the time of recruitment, 44 individuals with SCA under 18 years of age were

registered in the database. The response rate from the database was 47%.

The remaining seven participants were recruited at the annual meeting of the Norwegian

Klinefelter Syndrome Association in 2012. Information about the project that the current

thesis is a part of, was given at the meeting, and the attending families were invited to take

part. Six of the participants attending the meeting were also registered in the database. Mostly

adult men with KS attended this meeting, and were not invited due to age over 18. Number of

attendants was not noted, thus the response rate from this setting is unknown.

In both settings parents were given an envelope with the questionnaire and a stamped return

envelope. In the current thesis, analyses are based on responses for one parent, mainly

mothers. A total of 19 mothers (76%) and 6 fathers (24%) filled out the questionnaire.

Karyotype details were parent-reported, and details were checked in medical records for the

72% of the participants recruited from the database, and no discrepancies between parent

report and medical records were found. Access to medical records for the 28% recruited from

the user group meeting was not obtained. However, there is no reason to believe parents of

boys without SCA would be members of the Norwegian Klinefelter Syndrome Association.

2.1.2 Clinical sample

The participants in the clinical sample were drawn from the Assessment and Treatment -

Anxiety in Children and Adults study (ATACA: clinical trial no NCT00586586), a

randomized controlled trial (RCT) for which 221 children who were regular referrals to

community child and adolescent mental health clinics for anxiety related problems, were

assessed.

The clinical sample used in the current thesis, was comprised of 100 boys (mean age = 11.7

years, SD = 2.3, range 7-17 years) from the ATACA RCT. Since the SCA population in the

current thesis are boys, girls were excluded when drawing the clinical sample from the

ATACA RCT. For comparison, only boys’ scores were used for analyses. SES was estimated

to be high for 31%, medium for 50%, and low for 8%. SES was unknown for 11% of the

families (Currie et al., 2008). ATACA inclusion criteria were absence of severe conduct

disorder and/or mental retardation, and presence of separation anxiety disorder, generalized

anxiety disorder and/or social phobia. The clinical sample drawn for the current thesis

included all boys assessed for participation in the ATACA study that had complete data on

measures relevant to the current thesis.

The boys who were found to have problems of ASD symptomatology, low IQ or externalizing

problems, were excluded from the RCT. However, these were not excluded from analyses

included in the current thesis. It is important to note that these boys all were referred for

anxiety related problems, and should be considered to be representative of a clinical

population in the context of the current thesis.

Age differences

Age differences between the SCA sample (11.6 years) and the clinical sample (11.7 years)

was not significant (t = .094, p = .925, d =.01).

2.1.3 Norms

The current thesis uses Bishop et al.’s study on parent report of BI (2003) as norms for

comparison. The sample was comprised of 307 Australian boys (mean age= 4.1 years,

SD=5.9, range 3-5 years), drawn from a larger sample. For comparison reasons, girls were

excluded. SES was reported to be in the middle and upper categories of for 41.5% of families.

BI was parent-rated.

2.1.4 Research Ethics

Informed consent was obtained from the parents of the participants of the two Norwegian

samples (SCA & ATACA). The Regional Committee for Medical and Health Research Ethics

South East approved the SCA study, and the Regional Committee for Medical and Health

Research Ethics West approved the ATACA study.

2.2 Measures

The Behavioral Inhibition Questionnaire (BIQ) is a 30 item rating scale developed for use

with preschool children, scored on a 7 point Likert scale by parents and/or teachers (Bishop et

al., 2003). The BIQ measures BI in 6 domains, including in unfamiliar situations

(“Unfamiliar”: 8 items, maximum score 56), with unfamiliar peers (“Peers”: 6 items,

maximum score 42), with unfamiliar adults (“Adults”: 4 items, maximum score 28), in

separation/preschool situations (“Separation”: 4 items, maximum score 28), with novel

physical activities with a minor risk element (“Physical”: 4 items, maximum score 28), and in

performance situations (“Performance”: 4 items, maximum score 28), as well as a BIQ total

score (“Total”; 30 items, maximum score 210). Raters are asked to rate frequencies of

behaviors from “almost never ” to “almost always”. The contexts presented in the

questionnaire provide the foundation for the BIQ’s six subscales and cover the most important

aspects of the construct.

As many researchers consider BI to be a categorical variable, Bishop et al. (2003) decided to

divide the data set into high and low BI using the top and bottom 20% of scores on the BIQ as

cutoff for categorization.

Bishop et al. (2003) reported that the BIQ had good psychometric properties, with adequate

test-retest reliability for mothers and fathers as raters, stability was measured over 12 months.

Regarding inter rater reliability, total scores from mothers, fathers and teachers were

significantly correlated. Bishop et al. (2003) reports reliability estimates all above the

acceptable α value. α values for the BIQ total are to be considered excellent. Concurrent and

construct validity for the BIQ were found to be satisfactory, corresponding to other

temperament scales measuring BI. Confirmatory factor analysis supported six correlated

factors, each corresponding to one of the six subscales. All factors also loaded onto a single

higher-order construct, a general factor measuring overall BI. Using a large Australian

preschool sample (n = 495) , Kim et al. (2011) examined the BIQ’s psychometric properties,

and found support for the six factor structure corresponding to the subscales. Despite a

marginal model fit for teacher ratings compared to parent ratings, the study finds the BIQ to

have solid psychometric properties. Using the BIQ on a community sample in the Netherlands

with a much broader age range, Broeren and Muris (2010) found that the BIQ was a reliable

and valid measure not only for preschool children, but also for children aged 8-11 years and

12-15 years. For children aged 4-7 years (n = 172), they found that the BIQ total and

subscales “Adults” ,“Performance” and “Unfamiliar” were estimated to be excellent.

Reliability estimates for subscales “Peers” and “Separation” can be considered good. For 8-11

year-olds (n=146), they found estimates indicating that BIQ Total scores and subscales

“Adults” and “Unfamilar” yield reliability estimates to be considered as excellent. Subscales

“Performance” ,“Separation” and “Peers” can be considered good. In the group comprised of

12-15 year-olds (n = 213), BIQ Total is considered excellent. Subscales “Adults”,

“Unfamiliar”, “Peers” and “Separation” indicate a good level of clinical significance. See

Appendix 1 for Cronbach alpha values found in these studies.

In the current thesis, BIQ data from the SCA and clinical samples were rated retrospectively-

Parents rated their children at preschool age, the instruction being think back to how he was in

preschool (age 3 to 5 years).

2.2.1 Reliability estimates

Reliability analysis of the BIQ, including BIQ subscales, were calculated for the SCA

samples and the clinical sample. BIQ reliability scores in the norms were reported by Bishop,

Spence and McDonald (2003). Psychometric properties of the BIQ and values for the BIQ

total and BIQ subscales for each group are presented below, and α values are interpreted using

Cicchetti’s (1994) criteria; α less than .70, the level of clinical significance is considered

unacceptable; .70-.79, fair; .80-.89, good; .90 and above, the level of clinical significance is

excellent.

The BIQ total reliability was excellent for the SCA group (α =.95) with subscale reliability as

follows: “Unfamiliar” (α=.93) and “Separation”(α=.92), “Peers” (α=.85), “Adults” (α=.79),

“Physical” (α =.60) and “Performance” (α =.65).

The BIQ total was excellent for the clinical sample (α =.96), with subscale reliability as

follows:: “Unfamiliar” (α =.92), “Separation” (α =.91), “Adults” (α =.90), “Performance” (α

=.85), “Physical” (α =.82), “Peers” (α =.79).

2.3 Data analysis

Descriptive analyses were done using SPSS version 22.0. When the clinical sample and the

SCA sample were compared, independent sample t-tests were used. When both samples were

compared to norms, effect sizes were calculated using Cohen’s d (Cohens d=

[ 𝑀 𝑔𝑟𝑜𝑢𝑝 1 – 𝑀 𝑔𝑟𝑜𝑢𝑝 2

𝑆𝐷 𝑝𝑜𝑜𝑙𝑒𝑑] ) (Cohen, 1988). Effect size calculation was the only data analysis done

when comparing all three groups, as data from norms was limited to N, mean scores and

standard deviations only. Interpretation of effect sizes was done using Cohen’s (1992) criteria

(0.10 to 0.29 = small, 0.30 to 0.49 = medium, and >0.50 = large). Given the relatively small

sample size of the SCA group (N = 25) and the small number of participants in the SCA

subgroups of karyotypes 48,XXXY (N = 3) and 48,XXYY (N = 3), subsamples were not

distinguished in comparison analyses.

Another way of handling limited normative data, is doing analysis of variance from

summarized data. The calculations used can be thought of as a two-level ANOVA, and

equivalent to at t-test. Using this method, p-values for the SCA sample, normative sample,

and norms were calculated using the number of observations, means, and standard deviations

from each group, creating a surrogate data set (Larson, 1992; Pezzullo, 2016).

3 Results

BI scores

See Figure 1 for an overview of mean item scores and mean item standard deviations for the

total and subscales of the BIQ for the SCA, clinical and norm sample. In general, the scores of

the SCA and clinical sample were similar, and relatively higher than norms. Differences

between groups are illustrated with effect sizes. When comparing the SCA sample to the

clinical sample, a large effect size was found on subscale “Physical”. Medium effect sizes

were found on subscales “Separation” and “Peers”. When comparing the SCA sample to

norms, large effect sizes were found on the total score, as well as subscales “Peers”,

“Unfamiliar”, “Physical” and “Performance”. A medium effect size was found on subscale

“Separation”.

See appendix 2 for total and subscale scores and standard deviations, and appendix 3 for mean

item total and subscale scores and standard deviations.

3.1 Differences between the SCA sample, clinical sample,

and norms

Effect sizes

When compared to norms, the SCA sample scored significantly higher on most scales.

According to Cohen’s (1992) criteria, the BIQ Total and subscales “Peers”, “Unfamiliar”,

“Physical” and “Performance”, yielded large effect sizes.

Overall, comparing the SCA sample to the clinical sample yield small effect sizes, indicating

similar scores. A large effect size was found on subscale “Physical”, indicating that the SCA

sample was rated as significantly more inhibited than the clinical sample. Medium negative

effect sizes was found on subscales “Separation” and “Adults”, indicating that the clinical

sample was more inhibited than the SCA sample in these settings. See appendix 4 for a table

of effect sizes.

Analysis of variance from summary data

The p-values from analysis of variance from summary data displayed the same pattern as the

effect size calculations; when comparing the SCA group with the clinical group, only the

subscale Physical was statistically significant. When comparing the SCA group to the norm

group, several subscales were statistically significant. See appendix 5 for a table of p-values.

T-test

An independent samples t-test comparing the SCA sample and the clinical sample generally

showed the same tendency as the effect size calculations and the analyses of summary data.

The differences in scores between the two groups were not significant. The only subscale

where the two samples are significantly different, was the physical subscale.

Table 4. T-test comparing the SCA sample to the clinical sample

SCA Clinical

BIQ subscale M SD M SD t df p

Total 118.09 38.31 117.51 36.53 .067 119 .946

Separation 15.09 6.81 17.36 6.99 -1.409 117 .161

Peers 24.09 9.33 24.06 7.16 .013 116 .989

Adults 13.57 6.47 15.81 6.71 -1.452 117 .149

Unfamiliar 32.22 12.89 32.02 11.06 .074 115 .941

Physical 16.09 5.38 12.10 5.87 2.972 118 .004*

Performance 17.04 5.53 16.14 5.76 .680 119 .498

Note. **p<.01

Figure 1. BIQ comparison scores. Mean item scores and mean item standard deviations. Effect sizes comparing groups in grey, in order: norm vs SCA, SCA vs clinical

4 Discussion

Aiming to contribute to the knowledge about the temperament of boys with SCA, the current

thesis examined the temperamental trait of BI with the BIQ in a sample of Norwegian boys

with SCA. The sample was comprised of 25 boys with karyotypes 47,XXY, 47,XYY,

48,XXYY and 48,XXXY.

Knowledge of socio-emotional functioning and temperamental style in boys with SCA is

limited, and previous studies often use broad descriptions of personality, or refer to

personality in terms of behaviors seen as relatively independent of temperament. The terms

used to describe social personality or temperament in individuals with SCA are withdrawn,

shy, socially isolated, anxious. Most studies refer to adult personality, and psychometrics

varies: from measuring adolescent personality with an assessment instrument for

highschoolers and the projective test Draw-A-Person (Bancroft et al., 1982), to measuring

adult personality and motivational styles in individuals with learning disabilities (Visootsak et

al., 2007). Given the relative continuity from childhood temperament into adult personality,

BI, a temperamental trait that seemed relevant for boys with SCA, was examined.

First, parent-reported BI was studied within the SCA sample, aiming to examine whether

boys with SCA are behaviorally inhibited. The boys in the SCA sample were rated on and

above the middle on all subscales of the BIQ, indicating a temperamental style of high BI.

Second, the BI scores of the boys in the SCA sample were compared to a clinical sample,

aiming to answer whether the SCA sample’s scores were relatively elevated. The clinical

sample was comprised of boys referred to community mental health clinics for suspected

anxiety problems, and thus expected to be rated with a high degree of BI. The SCA and

clinical samples were generally scored similarly, although the boys from the SCA sample

scored significantly higher on BI in physical situations.

To further examine whether the SCA sample’s BI scores were relatively elevated, scores were

compared to a large norm group. When compared to norms, the SCA sample generally

sscored significantly higher on BI. These results indicate that the level of BI in boys with

SCA are as high as for a group of boys reffered to mental health clinics. Both groups have

scores indicating a higher degree of BI than in a general population.

Previous studies of boys with SCA suggest that these boys are a vulnerable group, with

increased risk of both physical and socio-emotional comorbidity. The current thesis has

examined the temperamental trait of BI based on similarity to typical personality descriptions

of boys with SCA. The finding that boys with SCA are behaviorally inhibited in many

domains, suggests that these boys have difficulties in participating in important activities with

peers in kindergarden, school, and leisure activities. These are important arenas for social,

cognitive and motor development, as well as friendship, mastery, self-esteem and general

quality of life.

4.1 SCA, BI, and physical activity

An important finding in the current thesis was that boys with SCA scored significantly higher

on physical aspects of BI, both compared to the clinical sample and to norms. This finding

indicates that boys with SCA might have significant problems with participating in play

involving physical activity with peers. A common finding among boys with SCA, is delayed

motor development, suggested to be caused by hypotonia (i.e., low muscle tone), and

hypermobility (i.e., flexible joints) (Ross et al., 2008; Simpson et al., 2003; Visootsak,

Aylstock, & Graham, 2001).

Based on findings of sex differences in levels of play involving physical activity in many

mammalian species, Pellegrini and Smith (1998) hypothesized that hormonal differences

might be important. One of the major endocrinological features that characterize boys with

SCA, is dysregulated hormonal secretion, found both in childhood and adulthood (Aksglæde

et al., 2011). In the context of the current thesis, it can be hypothesized that hormonal

differences in boys with SCA might influence the level of physical activity.

Boys with SCA have been found to have impaired gross motor function and coordination,

especially in running speed and agility (Ross, Zeger, Kushner, Zinn, & Roeltgen, 2009). By

mastering important skills like biking, skiing, and jumping later than their peers, these boys

might experience lack of self-efficacy from an early age. Experiencing one’s shortcomings

might result in withdrawal from physical activity, and thus reinforce motor delays. Several

other factors may also contribute as to why boys with SCA are more inhibited than their peers

in situations involving physical challenges. In the 2015 study of socio-emotional problems in

the same sample of boys as in the current thesis, Fjermestad et al. (2015) also examined

somatic problems. Frequent musculoskeletal pain was reported for a quarter of the SCA

sample. Social stigma associated with delayed puberty and gynecomastia could be a

significant hindrance for participation in physical education in school and organized activities.

Individuals with SCA have also been found to have increased risk of type 2 diabetes,

osteoporosis, and vascular disease later in life (Bojesen, Juul, Birkebæk, & Gravholt, 2006),

conditions that could make participating in physical activity difficult. However, these are

conditions that can be prevented or better managed with physical activity (Cox et al., 2016;

Prior, Barr, Chow, & Faulkner, 1996).

Physical play in childhood involves learning and practice of skills that are considered a

necessary part of becoming a functioning member of society. Whereas girls mainly establish

and maintain social dominance verbally, boys tend to use physical skills and play to adjust

peer group status (Eaton & Enns, 1986; Pellegrini & Smith, 1998). Based on the current

thesis, it can be hypothesized that being a physically inhibited and unassertive boy in a world

where boys are expected to take risks and participate in rough play, influences social function,

self-esteem, and relations in the peer group negatively.

4.2 SCA, BI, and orientation towards adults

A finding in the current thesis, is that the boys in the SCA sample were rated as less inhibited

with adults, and in separation situations than the boys in the clinical sample. Whether this is to

be attributed to more anxiousness with adults and separation in the clinical sample, or less in

the SCA sample, is unknown. Boys with SCA have been described as having problems in

relationships with peers (Bancroft et al., 1982), and in some cases, problems with social

responsivity (Cordeiro et al., 2012). It can be hypothesized that because they may be

experiencing problems in relating with peers, boys with SCA are more oriented towards

adults. A similar pattern has been found in individuals with ASD; children and adolescents

with ASD make fewer peer interactions than their normally developing peers, but rates of

interactions with adults are comparable to those of their peers (Hauck, Fein, Waterhouse, &

Feinstein, 1995; Orsmond, Krauss, & Seltzer, 2004).

Michael and Ben-Zur (2007) studied 269 Israeli adolescents (40.6% boys, M age = 16.6 years,

range 16-18), with the hypothesis that adolescents reporting a stronger orientation towards

their peer group, will be involved in more risk taking than those who look to adults. Degree of

orientation towards the peer group was measured by self-report of dependency and

conformity to the peer group, acceptance of group rules and discipline, as well as perceiving

the peer group as a source of help and power. It was found that for boys, risk-taking behaviors

were mainly related to a strong orientation towards the peer group. Sex differences were

found, with boys and girls engaging in risk-taking with different social orientations; Whereas

girls seemed to direct their adolescent risk-taking behaviors to parents, the boys’ behavior was

not moderated by parental influence to the same degree.

Boys with SCA are found to be inhibited in physical settings, and it can be hypothesized that

being both physically inhibited and having problems in social relations with peers, boys with

SCA might miss out on behaviors that are characteristic for the transitions that take place in

puberty and adolescence. An important part of adolescence, is that parent–child relationships

and relationships with peers change. If a certain level of risk-taking behaviors are important

for social relations with the peer group, and particularly so for boys, it seems reasonable to

assume that boys with SCA might have a disadvantage. At the same time, boys with SCA

have been found to have impaired inhibitory executive functions and problems with impulse

control (see Kompus et al., 2011; Ross, Stefanatos, Phil, & Roeltgen, 2007; Temple &

Sanfilippo, 2003), and risk-taking is not uncommon (Simpson, Graham, Samango‐sprouse, &

Swerdloff, 2005). Based on the current thesis, it can be hypothesized that boys with SCA

might involve in risk-taking that differs from the more socially adaptive and peer-oriented

risk-taking described by Michael and Ben-Zur (2007).

4.3 BI, social anxiety or problems with social functioning?

Many of the descriptions used to describe both boys with SCA and a temperamental style

characterized by high BI, are similar to descriptions of some of the aspects regarding social

functioning in ASD. The social discomfort found in children with a high degree of BI

resembles the social discomfort associated with social phobia, and this raises the question of

whether anxiety and BI simply are different names for the same phenomenon. BI and social

phobia share many common features, both behaviorally and biologically. Clauss and

Blackford (2012) argued that similar prevalence rates (BI as a toddler, and social phobia in

adolescence) might indicate that BI and social phobia are overlapping. However, many

children with high BI never develop anxiety disorders, and anxiety disorders are not always

preceded by BI (Hirshfeld et al., 1992). A multifinality perspective was suggested by Clauss

and Blackford (2012), i.e., that a common starting point such as high BI can take various

pathways. With a multifinality perspective, BI might be considered a component of later onset

social phobia, although the development of social phobia is also clearly affected by other

components. Relevant components that are possibly interacting with BI in boys with SCA, are

deficits in verbal skills, learning disabilities, and ASD-related symptoms.

4.4 The protective value of BI

BI is not always associated with dysfunction and distress, despite a large body of literature on

the adverse effects linked to a high degree of BI. Evidence of BI as a protective factor, comes

from studies of externalizing problems. ADHD is a neurodevelopmental disorder named after

its core symptoms of problems with paying attention and regulation of control, self, or

activity. The central deficit in ADHD has been argued to be a deficit in BI (Barkley, 1997),

indicating that BI might be a protective factor for externalizing disorders. This understanding

of BI is somewhat different from that of Kagan, Reznick, Snidman, et al. (1988). Where

Barkley’s definition of poor inhibition was used to describe an undercontrolled behavior

pattern, Kagan, Reznick, and Snidman (1988) have focused on the uninhibited child as

sociable and socially confident. Support for BI as a central deficit in ADHD was found when

Kerns, McInerney, and Wilde (2001) studied children with ADHD. Compared to healthy

controls, children with ADHD scored significantly lower on BI as well as attention. Studies of

shyness, anxiety, withdrawal and externalizing behavior such as aggression, criminality and

delinquency, have yielded results in very different directions. Some studies have hypothesized

and reported that shyness is a protective factor, while other studies have found that shyness

increases the risk of problem behaviors. Kerr et al. (1997) found BI to be a protective factor,

whereas social withdrawal was a risk factor. In social situations, behaviorally inhibited

children were less likely to perform deviant acts (e.g., cheating, using unfair strategies), and it

was hypothesized that inhibited children were less likely to interact with delinquent peers and

participate in situations where delinquent behavior occurs (Kerr et al., 1997).

However, boys with SCA have been reported to have a high prevalence of behavioral

problems and ADHD symptoms (Tartaglia et al., 2012). Hyperactivity and conduct problems

were assessed with the SDQ in Fjermestad et al. (2015) in the same sample used in the current

thesis. Medium effect sizes were found when the SCA sample was compared to a norm group.

The findings indicated that boys with SCA have more externalizing and less internalizing

problems than clinically referred boys, but that the total level of socio-emotional problems

may be as high as for the clinical sample (Fjermestad et al., 2015).

Evidence of both internalizing and externalizing problems in boys with SCA might mean that

these boys have a double disadvantage, despite a possible protective factor in having a high

degree of BI. Boys with SCA might miss out on socially important interactions with the peer

group, due to withdrawal, shyness, and communication difficulties. Knowing that boys with

SCA might have executive dysfunctions including lack of impulse control, it can be

hypothesized that boys with SCA could be experiencing conflict and chaotic situations that

are hard to handle. Situations with many misunderstandings and conflict might be particularly

troublesome for boys with a temperamental style that makes them want to avoid socially

difficult situations.

4.5 Strengths and limitations

The strengths of the current thesis include originality, as boys with SCA are an understudied

group. Several karyotypes of SCA are represented, included karyotypes with a low prevalence

that are not frequently included in studies of SCA. The thesis also includes a comparison

between the SCA sample and a large clinical sample and norms. The thesis examines a

temperamental trait that has proven to have important predictive value when it comes to

socio-emotional function, both current and later. BI involves aspects of functioning that are

known to be relevant for boys and men with SCA. The examination of BI in a group of boys

with SCA, represents a novel approach. However, there are also important limitations to

consider. These will be outlined below.

In terms of generalizability, the small size of the SCA sample limits generalizability, and

reduces statistical power. However, SCA conditions are rare, and the current thesis uses data

from 47% of known cases registered in the database at Frambu resource centre for rare

disorder, which means that a large proportion of the boys with a known diagnosis of SCA

participated.

The SCA sample was comprised of boys with four different karyotypes. There is agreement

that there are differences in phenotype between the various karyotypes, but at the same time,

some common features. In addition, there is great variability among individuals. Data

analyses were done on the data from the SCA sample as one sample, as the small sample size

of some of the karyotypes would have limited generalizability and statistical power.

Standard newborn screening in Norway does not include screening for SCA conditions,

leading to these conditions being highly underdiagnosed. In terms of recruitment methods,

recruitment from clinical settings, such as the Frambu database and user groups might subject

the current thesis to ascertainment bias, and an overestimation of problems, and may not be

representative for the undiagnosed SCA population.

The boys in the ATACA study were not screened for SCA conditions, and it is not known

whether any participants had a SCA condition.

In terms of age range, the age range of the SCA sample is wide. Range stretched from 2-18

years. When parents rated their children, they were asked to rate their child’s behavior at

toddlerhood, meaning that some parents rated the children at present time, but most rated their

children retrospectively. Thus, parents may be subject to recall bias. Parents might also be

subject to stereotypical views of their children, and these stereotypes might be resistant to

actual change in children. BI is a temperamental trait, only moderately stable. Retrospective

rating of BI was also the case for the clinical sample, but not for the norms, which might limit

comparison.

The current thesis uses an Australian sample as norm for comparison, and this raises three

methodological challenges; the norm sample differs from the two Norwegian samples in age,

time of rating and culture. The norm sample had a lower mean age and narrower age range,

whereas the SCA and clinical samples had higher mean ages and wider age ranges. Due to the

wide age ranges, the SCA and clinical samples were rated retrospectively, whereas the

children from the norm group were rated concurrently. The use of a norm group from

Australia raises the question of whether the cultural and sociodemographic differences might

be a limitation. However, at the present, no Norwegian normative sample has been rated on

the BIQ.

Using data from Bishop et al. (2003) study as norms, limited some analyses, as only means

and standard deviations were available for analysis. In addition to effect size calculations,

analysis of variance from summary data was used. This method is currently not widespread,

and results derived from it must be interpreted with caution.

Regarding rating methods, the current thesis used data generated mainly by mothers rating

their sons. The boys themselves or fathers might be just as valid sources of information.

However, young children have limited expressive and receptive language skills, which limits

self-report for the youngest subjects, and when comparing ratings from mothers and fathers to

observational data, Bishop et al. (2003) found that fathers were less sensitive to BI related

behavior in their child.

When it comes to BI as a variable, there are some methodological issues. BIQ offers no cutoff

scores for interpretation, as Bishop et al. (2003) argues that there is an ongoing debate of

whether BI is a categorical or continuous variable. Information about BI in the samples

examined in the current thesis, is derived from scores on a questionnaire (BIQ), and is thus

categorical. No additional data on BI specific behaviors were collected. In their 1987 article,

Kagan and Snidman argued that a categorical approach gave a better fit for their data, and

found support in empirical tests of the data structure. Arguments for a continuous perspective

comes from longitudinal studies, such as that of Muris, van Brakel, Arntz, and Schouten

(2011). In their study of 124 behaviorally inhibited children and 137 control children from the

Netherlands aged 5 to 8 years, childhood BI significantly predicted the degree of social

anxiety at 1 and 2 years later. However, Bishop et al. (2003) argued that indicators of both a

categorical and continuous construct, are behaviorally based, and that the consequence is

different methods of assessment (questionnaire if categorical, observation if continuous). The

choice of comparing to a clinical sample and norms, addresses the lack of cut-off scores, and

allows relative comparison.

In terms of design, Clauss and Blackford (2012) proposed that both categorical and

continuous approaches are useful when measuring BI. Some studies have combined

observational data, parent-reported data and/or self-report. A design where examination

allowed both a categorical and continuous perspective on BI, would possibly have solved

some methodological issues in the current thesis. However, given the fact that SCA are rare

conditions, a wide age range had to be accepted, and this narrowed available methods of

examination.

In light of the methodological issues presented above, results from the current thesis should

be interpreted with caution.

4.6 Ethics

An important ethical weakness, is that for the SCA sample, only parents gave informed

consent. Some of the participants were as old as 18 years, and should have been given the

opportunity to consent themselves. Answering problem-focused questions about their boys,

might be a burden for parents, and contribute to a view of their children in terms of

difficulties. The problematic aspects of BI in boys with SCA presented in this thesis, is thus

contributing to the already problem-focused literature on boys with SCA. An deterministic

interpretation of results should be avoided, as there is evidence of great variability among

individuals and discontinuity from early temperament to later functioning.

4.7 Clinical implications

Research on BI has documented that being inhibited predicts later onset anxiety.

Temperamental styles or characteristics are not diagnoses, and neither is the relationship

between early BI and later psychopathology linear. Screening for BI in the context of

predicting anxiety, would yield many false positives, and as a result, potentially lead to

overtreatment, as most inhibited toddlers never develop social anxiety as teenagers (Svihra &

Katzman, 2004). However, BI has been associated with a greater risk for later onset social

anxiety for some children. In the current thesis, scores on BI in boys with SCA conditions

were found to be as high as in boys referred to community mental health clinics for anxiety

problems. Other studies have found boys with SCA to have considerable socio-emotional

problems, including anxiety (Bruining, Swaab, Kas, & van Engeland, 2009; Fjermestad et al.,

2015; Ross et al., 2012). The current thesis hypothesizes that BI could be one of the aspects

that make boys with SCA vulnerable and at risk for developing anxiety.

Following diagnosis of SCA involving supernumerary X chromosomes, many boys receive

testosterone treatment and relevant medical treatment of common endocrinological and other

medical conditions associated with SCA. Those who have learning disabilities or learning

difficulties might be offered educational counseling or habilitation services in

kindergarten/school. Some children are referred to community mental health clinics.

However, Fjermestad et al. (2015) reported that only 2 of the boys in the SCA sample

received help from a psychologist. This means that boys with SCA might have a need for

screening and treatment that currently is not met. Considering that behavioral inhibition can

be identified earlier in life than manifest anxiety, repeated confirmation of these findings

could have important implications for the prevention of anxiety disorders in boys with SCA,

and that screening of mental health and social problems should be included in standard care

The boys with SCA examined in this thesis, had high scores on inhibition in physical settings.

Physical activity and assertiveness plays an important part of motor and social development,

and is central to the prevention and/or management of both psychological and somatic

problems. Psychoeducation for parents, teachers and health care professionals concerning

physical activity, aimed at encouraging boys with SCA to master and enjoy physical activity,

could be useful. It is currently not standard care for boys with SCA, but given a motor

difficulty or disability, physiotherapy might be indicated.

Knowledge of BI could be an integrated part of psychoeducation offered to parents of boys

with BI, helping parents understand their sons and the challenges they might experience in

various situations. In an American study of early intervention of anxiety disorders in 146

inhibited children aged 3 to 5 years, Rapee, Kennedy, Ingram, Edwards, and Sweeney (2005),

found that parent-education reduced risk of anxiety 12 months later. The parent-education

program included psychoeducation about anxiety (e.g., over-protective parenting and

cognitive restructuring of the parent’s own worries, exposure hierarchies and high-risk

transition periods). Although inhibition was not significantly reduced, the adverse effects (i.e.,

anxiety) were. The authors’ conclusions were that the results indicate that despite the fact that

temperamental traits seem hard to modify, it might be possible to create interventions for

some common outcomes that affect mental health and well-being (Rapee et al., 2005).

4.8 Research implications

Using combined methods such as both parent-reported retrospective rating and self-reported

measures of aspects relevant to BI in adolescent or adults with SCA, could be a future

examination of stability in BI in boys with SCA. The inclusion of observational data would

further strengthen findings.

Inhibition in physical settings for boys with SCA is an important finding from the current

thesis, an insight that might suggest that further research on the relationship between physical

activity and social problems could be fruitful when creating guidelines for parents and health

care professionals working with these boys. Given the musculoskeletal pain and somatic

complications that boys with SCA are at risk of developing, this is an important area for

intervention.

There has been established evidence of early BI and later psychopathology in several studies,

and future research need to address whether measures of BI is an adequate method for

predicting which children are at risk of developing internalizing problems. Little is still

known of why some high BI children develop internalizing problems and some do not. Better

knowledge of both biological and environmental factors influencing risks and resilience, is

necessary to create preventative interventions.

5 Conclusions

The temperamental style of boys with SCA has been examined in the current thesis. BI was

rated in a sample of 25 Norwegian boys with SCA, and the boys with SCA were scored as

high as a clinical sample on most aspects of BI. Both the SCA and the clinical sample were

scored significantly higher than norms. Given that BI is considered an important predictor of

later onset anxiety, boys with SCA might have the same need for psychological assessment as

clinic-referred boys.

The current thesis has aimed to contribute to the knowledge of a clinically relevant

temperamental trait in boys with SCA, an understudied group.

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Appendixes

Appendix 1. Cronbach’s alpha values for BIQ subcales

Study

Broeren and

Muris (2010)

Kim et

al.

(2011)

Bishop et

al. 2003

(norms)

ATACA

(clinical

sample)

SCA

sample

Age 4-7 8-

11

12-

15

M=3,5 3-5 7-17* 2-18*

N 172 146 213 559 611 221 25

BIQ Total .96 .95 .95 >.80 .95 .96 .95

Separation .84 .86. .79 >.80 .90 .91 .92

Peers .89 .84 .87 >.80 .90 .79 .85

Adults .92 .92 .89 >.80 .91 .90 .79

Unfamiliar .91 .92 .89 >.80 .90 .92 .95

Physical .79 .67 .73 .74 .80 .82 .60

Performance .90 .83 .87 >.80 - .85 .65

Note. * Parents of older participants asked to score children retrospectively

Appendix 2. BIQ total and subscale scores

Sample

SCA

(n = 25)

Clinical

(n = 98)

Norm M

(n = 307)

BIQ scale M

(SD)

Total 118,09 (38,31)

117.51 (36.53)

89.71 (31.32)

Separation 15.09 (6.81)

17.36 (6.99)

11.97 (6.37)

Peer 24.09 (9.33)

24.06 (7.16)

18.99 (8.30)

Adult 13.57 (6.47)

15.81 (6.71)

13.59 (6.09)

Unfamiliar 32.22 (12.89)

32.02 (11.06)

23 (8.77)

Physical 16.09 (5.38)

12.1 (5.87)

9.11 (5.08)

Performance 17.04 (5.53)

16.14 (5.76)

13.06 (5.31)

Appendix 3. Mean item BIQ total and subscale scores

Sample

SCA

(n = 25)

Clinical

(n = 98)

Norm M

(n = 307)

BIQ scale (items)

M (SD)

Total (30) 3.94 (1.04)

3.92 (1.28)

2.99 (1.22)

Separation (4) 3.77 (1.59)

4.34 (1.70)

2.99 (1.75)

Peer (6) 4.02 (1.38)

4.01 (1.56)

3.17 (1.19)

Adult (4) 3.39 (1.52)

3.95 (1.62)

3.40 (1.68)

Unfamiliar (8) 4.03 (1.10)

4.00 (1.61)

2.88 (1.38)

Physical (4) 4.02 (1.27)

3.03 (1.35)

2.28 (1.47)

Performance (4) 4.26 (1.33)

4.04 (1.38)

3.27 (1.44)

Appendix 4. Effect sizes

Sample

BIQ scale SCA vs

clinical

SCA vs norm

Total 0.02 0.81**

Separation -0.33* 0.47*

Peers 0.01 0.58**

Adults -0.34* -0.01

Unfamiliar 0.02 0.84**

Physical 0.71** 1.33**

Performance 0.16 0.73**

Note. * Medium effect size, ** Large effect size, when using Cohen’s (1992) criteria (0.10 to

0.29 = small, 0.30 to 0.49 = medium, and >0.50 = large).

Appendix 5. Analysis of variance from summary data

Sample

BIQ scale SCA vs

clinical

SCA vs norm

Total .995 <.001**

Separation .294 .071

Peers .995 .011*

Adults .272 .995

Unfamiliar .995 <.001**

Physical .004** <.001**

Performance .754 .002**

Note. Results presented in p-value *p<.05 **p<.01