Received: 31 August 2022

| Revised: 8 January 2023 | Accepted: 23 January 2023

DOI: 10.1002/pcn5.80

ORIGINAL ARTICLE

Relationship between high trait anxiety in 22q11.2
deletion syndrome and the difficulties in medical, welfare,and educational services
Naomi Nakajima PhD1
| Miho Tanaka PhD1 | Akiko Kanehara PhD1 |Ryo Morishima PhD2,3 | Yousuke Kumakura MD1,4 | Noriko Ohkouchi PhD1
1

5

Junko Hamada MA | Tomoko Ogawa MA | Hidetaka Tamune MD, PhD
Mutsumi Nakahara PhD8 | Shunsuke Mori MD3 | Kayo Ichihashi MD1 |Seiichiro Jinde MD, PhD1,3 | Yukiko Kano MD, PhD5,9
Kyoko Tanaka MD, PhD11 | Yoichiro Hirata MD, PhD12
13|
Hirofumi Ohashi MD, PhD
1,3,15,16
Kiyoto Kasai MD, PhD

Tokuko Shinohara MD

14

6,7

|
|

| Ichiro Sakamoto MD10

|

|
|

1

Department of Neuropsychiatry, The University of Tokyo Hospital, Tokyo, Japan

2

The Health Care Science Institute, Tokyo, Japan3

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4

Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

5

Department of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan

6

Department of Cellular Neurobiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

7

World‐Leading Innovative Graduate Study Program for Life Science and Technology (WINGS‐LST), The University of Tokyo, Tokyo, Japan

8

Graduate School of Clinical Psychology, Kagoshima University, Kagoshima, Japan

9

Department of Child Neuropsychiatry, Graduate, School of Medicine, The University of Tokyo, Tokyo, Japan10

Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

11

Department of Psychosocial Medicine, National Center for Child Health and Development, Tokyo, Japan

12

Department of Pediatrics, Kitasato University School of Medicine, Kanagawa, Japan

13

Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan

14

Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, Tokyo, Japan

15

The International Research Center for Neurointelligence (IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Tokyo, Japan

16

UTokyo Institute for Diversity and Adaptation of Human Mind (UTIDAHM), The University of Tokyo, Tokyo, Japan

Correspondence
Kiyoto Kasai, MD, PhD, Department of
Neuropsychiatry, The University of Tokyo
Hospital, 7‐3‐1 Hongo, Bunkyo‐ku,
Tokyo 113‐8655, Japan.
Email: kasaik-tky@umin.net

Abstract
Aim: The 22q11.2 deletion syndrome (22q11DS) is associated with a high prevalence ofmental health comorbidities. However, not enough attention has been paid to theelevated prevalence of high trait anxiety that begins early in life and may be enduring.
We sought to identify specific medical, welfare, or educational difficulties associatedwith high trait anxiety in 22q11DS.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and
Neurology.
Psychiatry Clin. Neurosci. Rep. 2023;2:e80.
https://doi.org/10.1002/pcn5.80

wileyonlinelibrary.com/journal/pcn5|

1 of 9|

HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME

Funding information
University of Tokyo, Grant/Award Numbers:
IRCN, UTIDAHM; Japan Science andTechnology Agency, Grant/Award Number:Moonshot R&D Grant Number JPMJMS2021;
Japan Society for the Promotion of Science,
Grant/Award Numbers: JP20H03596,
JP21H05171, JP21H05174

Methods: A questionnaire‐based survey was conducted for the parents of 22q11DS
individuals (N = 125). First, a multiple regression analysis was conducted to confirm the
hypothesis that high trait anxiety in individuals with 22q11DS would be associated withparents' psychological distress. This was based on 19 questionnaire options regarding
what difficulties the parents currently face about their child's disease, characteristics,
and traits. Next, we explored what challenges faced in medical, welfare, and educational
services would be associated with the trait anxiety in their child.
Results: The multiple regression analysis confirmed that the high trait anxiety wassignificantly associated with parental psychological distress (β = 0.265, p = 0.018) amongthe 19 clinical/personal characteristics of 22q11DS. Furthermore, this characteristic
was associated with various difficulties faced in the medical care, welfare, and education
services, and the parent–child relationship.
Conclusion: To our knowledge, this is the first study to clarify quantitatively how thecharacteristic of high anxiety level in 22q11DS individuals is related to the caregivers'
perceived difficulties in medical, welfare, and educational services. These results suggest
the necessity of designing service structures informed of the fact that high trait anxiety
is an important clinical feature of the syndrome.
KEYWORDS

22q11.2 deletion syndrome, anxiety, caregiver, educational, medical, welfare

individuals.8 Schneider and colleagues9 reported that people withI NTR O D U C TI O N

22q11DS experienced increased negative affect throughout theThe 22q11.2 deletion syndrome (22q11DS) is caused by the

day and a greater frequency of events that are perceived as

microdeletion of chromosome 22 with an incidence rate ofunpleasant as compared to controls.

1

1/6000−1/3000. Many individuals with 22q11DS present congeni-

However, a previous study reported that anxiety disorders intal physical conditions, such as congenital heart disease, characteris-

individuals with 22q11DS often go undiagnosed and untreated, as

tic facial features, and immunological problems. Additionally, they

only 19% of those participants were diagnosed with an anxiety

often co‐develop neurodevelopmental disorders, such as intellectual

disorder, even though 58% presented significant anxiety symptom

and learning disabilities, attention deficit hyperactivity disorder

scores.10 It has been reported that the mental health conditions(ADHD), and autism spectrum disorder (ASD), as well as psychiatricidentified in children with 22q11DS are inadequately treated.11,12

disorders, such as anxiety and psychotic disorders.

2,3

Furthermore, high levels of anxiety were associated with impaired

Complications of schizophrenia and developmental disorders

adaptive functioning,5,10 and the baseline anxiety symptom washave been highlighted in the literature as psychiatric symptoms

associated with an increased risk of schizophrenia at the 5‐year

associated with 22q11DS. The onset of schizophrenia usuallyfollow‐up in 22q11DS children. 13

occurs during adolescence, with an estimated lifetime prevalence

It is not yet clear how these anxieties are linked to difficulties

of approximately 20%−25% in 22q11DS patients.2,3 On the

faced by individuals and their caregivers in medical, welfare,other hand, ADHD and ASD are usually diagnosed in childhood,and education services. However, clarifying this could help to4

provide better support to the individuals, and alleviate the

Although not documented sufficiently, the prevalence ofanxiety and stress levels along the developmental pathway,anxiety disorders in children and adolescents with 22q11DS isleading to better social adjustment, reduced risk of psychosis,

reportedly 35.6% and 33.9%, respectively.4 Among these anxiety

and reduced burden of care and distress for the family.

disorders, specific phobias (17.0%−21.9%), social phobia or social

Accordingly, thisanxiety (9.8%−10.3%), and generalized anxiety disorder (8.3%that the presence of high trait anxiety level is associated−10.5%) are the most common in children and adolescents.4

with parental distress among various perceived difficulties

Previous studies have shown that individuals with 22q11DS haveregarding their children's clinical and personal characteristics.

high levels of trait anxiety throughout their lives. 4–7 Additionally,Thus, we examined how high trait anxiety was associated withchildren with 22q11DS are more likely to experience repetitive or

difficulties faced in receiving medical care, welfare, and education

chronic stress, including bullying, than typically developing

services.

with an estimated prevalence of 37.1% and 12.8%, respectively.

study

aimed attestingthehypothesis

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2 of 9METHO DS
Development and implementation of the survey

3 of 9T A B L E 1 List of the 83 questionnaire items representing
parental difficulties faced in medical care, welfare, education
services, and other areas
Perceived challenges in parent–child relationships (4 items)

A detailed description of the methodology of our primarily web‐based

1‐1

Verbal communication

1‐2

Proximity with parents

related to medical care, education, and welfare services faced by those

1‐3

Difficulty becoming independent

affected by 22q11DS. It was developed based on previous literature and1‐4

Defiance or opposition

clinical guidance,2,16–18 and with the assistance of two parents caring for

Perceived challenges in medical care services (12 items)

survey is available in our previous studies.14,15 Briefly, this anonymous
online questionnaire survey recorded the challenges and support needs

an individual with 22q11DS. The final version of the survey questionnaire

2‐1Lack of information regarding 22q11.2 deletion syndrome2‐2Lack of knowledge on the part of medical staff (doctors, nurses,etc.) regarding 22q11.2 deletion syndrome

22q11DS; parental psychological distress; and various challenges faced in

2‐3Attitude of medical staff

medical care, welfare, education services and in the coordination between

2‐4Lack of explanation from medical staff

them and other areas, including child–parent relationships and transition

2‐5

Difficulty in decision‐making with regards to medical care

2‐6Informing the child of their 22q11.2 deletion syndrome
diagnosis

2‐7Selecting a hospital for treatment

used for the quantitative measurement of parental psychological

2‐8Difficulty of going to multiple medical institutions

distress. The participants rated the items (e.g., “During the past

2‐9Unable to receive comprehensive treatment due tomultimorbidity

could cheer you up?”) on a five‐point Likert‐type scale ranging from

2‐10

Difficulty in selecting a hospital for mild diseases/symptoms

0 (none of the time) to 4 (all of the time). The final score is a sum of all

2‐11

Individual with 22q11.2 deletion syndrome unable to undergo aconsultation by his/herself

2‐12

No medical institution allows parents to come for consultations
if the child with 22q11.2 deletion syndrome is unable toundergo a consultation

was divided into 10 domains, as described in detail in our previous
study.15 In this study, we used the data on parental demographics; patient
demographics; lifetime diagnosis of comorbidities in individuals withfrom child to adult medical care. Respondents were instructed to answer“yes” or “no” to each of the questionnaire items as listed in Table 1.
The Kessler 6 Scale (K6), a six‐item screening measure fornonspecific psychological distress during the past 30 days,19 was

30 days, about how often did you feel so depressed that nothing

the response scores, with a possible range of 0−24, and higher scoresindicated more severe psychological distress.
The response period was from March 20 to November 8, 2019.
Access to the web questionnaire was set up on our research team
web page (“22q‐pedia”; https://22q-pedia.net/). The survey was
publicized to the patients' families by e‐mails and/or letters with thePerceived challenges in welfare services (21 items)
3‐1

Although three disabilities are overlapping (physical, intellectual,and mental), the system (disability certificate, disability
pension, etc.) is divided vertically into physical disabilities,
intellectual disabilities, and mental disabilities, and the
difficulty of overlapping disorders when filing applications
has not been considered

3‐2Unable to receive intractable disease certification

3‐3Lack of information regarding development‐related support,such as rehabilitation

3‐4Lack of consultants and contacts regarding development‐related
support, such as rehabilitation

3‐5Lack of development‐related support

3‐6

Lack of information on welfare services

3‐7Lack of consultants and contacts regarding welfare services

3‐8Lack of knowledge on the part of supporters (welfare facility
personnel and government personnel) regarding 22q11.2
deletion syndrome

3‐9

No welfare facilities suitable for the characteristics and traits of
the individual with 22q11.2 deletion syndrome

3‐10Unable to go to the welfare facility even if one is available

help of the Japanese 22q11DS family association (22 HEART CLUB),
the Association for the Protection of Children with Heart Disease,and people involved in the medical care of individuals with 22q11DS.
Therefore, the recruited population was not defined, and thecollection rate could not be calculated. For participants who foundit difficult to answer the web questionnaire, a physical form of thequestionnaire was mailed to them upon request. Of the 125 valid
responses, four were received in the paper questionnaire form.

Participants
The demographic and clinical information of the individuals with
22q11DS and their parents who participated in the survey werereported in detail in our previous study.15 A summary of thedemographic information and physical, developmental, and psychiatric comorbidities is provided in Table 2.
This study was approved by the Ethics Committee of the Facultyof Medicine, The University of Tokyo (approval No. 2018015NI). The
participants expressed their consent to participate in the study by
responding to the questionnaires. As a reward for participation, we(Continues)

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HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME|HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME

TABLE 1

(Continued)

TABLE 1

(Continued)

3‐11Lack of home care/visiting services

4‐23

Cannot come to an agreement with the school regarding the
educational policy for children with 22q11.2 deletion
syndrome

3‐12

No support available when parents are exhausted and need a
respite3‐13

Lack of information about employment

4‐24

You (parent/guardian) or your family's anxiety or resistance toselecting a special class or schools for special needs education

3‐14

Lack of consultants and contacts regarding employment support

3‐15

No job opportunities

4‐25

Anxiety or resistance that the individual feels on selecting a
special class or schools for special needs education

3‐16

Unable to remain employed for extended periods

Perceived challenges in coordinated support (6 items)

3‐17Lack of understanding in the workplace

5‐1

3‐18

Lack of help/support in daily life

Lack of coordination between the clinical field (hospitals, etc.)
and welfare services (daycare facilities, etc.)

3‐19Lack of residences, such as group homes

5‐2Lack of coordination between the clinical field and education
services (schools, etc.)

3‐20

Concerns about marriage

5‐3Lack of coordination between welfare and education services

3‐21

Concerns about pregnancy and childbirth

5‐4Lack of consultants or contacts for comprehensive consultations
regarding 22q11.2 deletion syndrome

5‐5Lack of comprehensive support for multimorbidities ordisabilities

5‐6

Existing medical, welfare, and educational support services do
not fit the individual's characteristics/traits with respect tothe 22q11.2 deletion syndrome, and there is no place forthem to go

Perceived challenges in education services (25 items)
4‐1

Preschool/kindergarten staff were unhelpful

4‐2

Reluctance to attend kindergarten or preschool

4‐3

Lack of information regarding school selection

4‐4Lack of consultants or contacts regarding school selection

4‐5

No educational institutions suitable for the individual's
characteristics/traits with respect to 22q11.2 deletion
syndrome

Perceived challenges in transition from child to adult medical care (15 items)
6‐1

Individual has not been informed of their diagnosis

6‐2

Lack of understanding of the disease on the part of theindividual with 22q11.2 deletion syndrome

6‐3

Selecting a hospital for adult medical care

6‐4Difficulties accompanying severe physical disorders

6‐5

Primary care physician is unable to address psychiatric
symptoms and psychosocial issues

Teachers of the schools for special needs education wereunhelpful

6‐6

Refused treatment by psychiatric departments due to physicaldisorders and physical symptoms

4‐12

Cannot keep up with school work

6‐7

Refused treatment by non‐psychiatric departments due topsychiatric disorders and psychiatric symptoms

4‐13

Difficulty participating in events, such as field days andschool festivals

6‐8Stress of the need to consult multiple medical institutions

4‐14

Difficulty making friends

6‐9Stress of the need to consult multiple clinical departments evenin the same hospital

4‐15

Refusal to attend school
6‐10

Lack of specialized medical institutions

4‐16

Being bullied
6‐11

4‐17

What activities to do after school

4‐18

Participating in extracurricular lessons and activities

Difficulties with coordinating transfers to a different clinicaldepartment (within the same hospital) or to a different
hospital

4‐19Communicating with the home room teacher

6‐12Differences in atmosphere and response between pediatric andadult medical care

4‐20

Change of home room teacher
6‐13

4‐21

Lack of knowledge of the school staff (faculty, etc.)
regarding 22q11.2 deletion syndrome

When transitioning to adult medical care, co‐payment for
medical expenses is required, which is a significant financial
burden4‐22Lack of understanding of the school staff (faculty, etc.)of the fact that children with 22q11.2 deletion syndrome
may need more individual attention
than those with ordinary physical or intellectual disabilities

6‐14

Lack of adult medical institutions offering comprehensive care

6‐15

No particular difficulties

4‐6Lack of special classes/schools for special needs education

4‐7

Lack of institutions for higher education for individual with
22q11.2 deletion syndrome

4‐8Lack of home/visiting educational services

4‐9

Regular class teachers were unhelpful

4‐10Special class teachers were unhelpful

4‐1127692558, 2023, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/pcn5.80 by Cochrane Japan, Wiley Online Library on [25/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

4 of 9TABLE 2

TABLE 2

Descriptive statistics of the study participants

Parents

5 of 9(Continued)

Parents

Age (years), mean (SD)

44.3

(7.5)

Epilepsy

19(15.2)

Mother, N (%)

114(91.2)

Other neuropsychiatric disorders

7

(5.6)

Father, N (%)

11

(8.8)

24

(19.2)

0−2.99 million yen

13(10.4)

3−5.99 million yen

36(28.8)

6−8.99 million yen

42(33.6)

9−11.99 million yen

11

(8.8)

12−14.99 million yen

13(10.4)

15−17.99 million yen

1

(0.8)

≧18 million yen

6

(4.8)

Unknown

3

(2.4)

5.0

(4.6)

Age (in years), mean (SD)

11.8a

(7.7)

Male sex, N (%)

63(50.4)For the question, “In supporting your child who has 22q11DS as a

Total number of lifetime comorbidities, mean (SD)

4.4

(1.8)

family member, what difficulties do you currently face (in the past

Annual household income, N (%)

Kessler 6 score, mean (SD)

Other
Abbreviation: SD, standard deviation.

Individuals with 22q11.2 deletion syndromea0−5 years: n = 33; 6–11 years: n = 35; 12–18 years: n = 28; over 19
years: n = 29.

distributed prepaid cards equivalent to 5000 yen (approximately 45
USD) in value to each respondent.

Data analysis
Analysis I: Confirmation of the hypothesis of significant
association between children's high trait anxiety(among many characteristics) and parental distressyear) regarding his/her disease, characteristics, and traits?”, respon-

Lifetime comorbidities, N (%)

dents were instructed to answer “yes” or “no” to the following

Congenital heart disease106(84.8)

Immune system disorders

38(30.4)

diseases; (2) repeated infections; (3) hampered motor functions/skills;

Endocrine disorders

48(38.4)(4) short stature; (5) articulation disorder (pronunciation/articulation);

Gastrointestinal diseases

36(28.8)

Otorhinolaryngology/maxillofacial diseases

94(75.2)

Orthopedic diseases

51(40.8)

19 options, with an additional item for free writing: (1) cardiovascular(6) speech delay; (7) intellectual disability; (8) arithmetic difficulties;(9) difficulty communicating with others; (10) restricted and/or
repetitive behavior; (11) temper tantrums; (12) hyperacusis; (13) hightrait anxiety; (14) selective mutism; (15) inability to join groups;(16) socially withdrawn; (17) easily tired; (18) hallucinations/delu-

Growth/developmental disorders

sions; (19) excitement/violence; (20) other (free writing). To test ourIntellectual disability

80

(64)

Autism spectrum disorder

12

(9.6)

Attention deficit hyperactivity disorder

8

(6.4)

19 items, we conducted a multiple regression analysis (forced entry

Oppositional defiant disorder

1

(0.8)

method). This analysis was conducted using the aforementioned

Learning disability

22(17.6)

19 items along with parental gender, parental age, child's gender,

Speech delay73(58.4)

Selective mutism

6

(4.8)

Delayed motor development

55

(44)

Growth disorder/short stature34(27.2)

Other growth/developmental disorders

6

(4.8)

Schizophrenia

8

(6.4)

Next, we determined which of the 83 questionnaire items of the

Major depression

1

(0.8)

parental difficulties in medical care, welfare, education services, andBipolar disorder

2

(1.6)

others (Table 1) were associated with the parents' perceived child's

Anxiety disorder (including panic disorder)

13(10.4)

Obsessive–compulsive disorder

4

(3.2)

hypothesis of whether the characteristic of high trait anxiety (Item#13) was significantly associated with parental distress among thesechild's age, and household income (a total of 24 items) as independent
variables, and the parental K6 score as the dependent variable.

Analysis II: Exploratory analysis for association
between children's trait anxiety and various difficulties
faced by parents

Psychiatric/neurological disorders

trait anxiety. For this, an exploratory analysis using χ2 test was
conducted to examine whether there was a difference between thegroups that answered “yes” (N = 33) and “no” (N = 92) to “#13: high27692558, 2023, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/pcn5.80 by Cochrane Japan, Wiley Online Library on [25/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License|

HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME|HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME

TABLE 3Item #

Summary of 19 items that were significantly different in the χ2 test comparing groups with and without high trait anxiety.

Item

χ2

Uncorrected p

FDRcorrected p

1. Perceived challenges in parent–child relationships
1‐1

Verbal communication

7.748

0.005380.0241

1‐2Proximity with parents

10.2560.001360.0103

1‐3

Difficulty becoming independent

8.022

0.004620.0226

1‐4

Defiance or opposition

9.904

0.00165

0.011414.6850.000130.0026

2. Perceived challenges in medical care services
2‐6

Informing the child of their 22q11.2 deletion syndrome diagnosis

3. Perceived challenges in welfare services
3‐8Lack of knowledge on the part of supporters (welfare facility personnel
and government personnel) regarding 22q11.2 deletion syndrome

10.9840.00092

0.00983‐9No welfare facilities suitable for the characteristics and traitsof the individual with 22q11.2 deletion syndrome

21.2720.000004

0.00033‐13

Lack of information about employment

9.3

0.002290.0132

3‐15

No job opportunities

16.4220.00005

0.00213‐18

Lack of help/support in daily life

9.22

0.002390.0132

13.6980.000210.00304. Perceived challenges in education services
4‐19Communicating with the home room teacher

5. Perceived challenges in coordinated support
5‐5Lack of comprehensive support for multimorbidity or disabilities

8.064

0.00452

0.0226

5‐6

Existing medical, welfare, and educational support services do not fit the individual's
characteristics/traits, and there is no place for them to go

10.8850.00097

0.0098

6. Perceived challenges in transition from child to adult medical care
6‐2Lack of understanding of the disease on the part of the individualwith 22q11.2 deletion syndrome

13.8340.000200.0030

6‐3

Selecting a hospital for adult medical care

10.6460.001100.0098

6‐5

Primary care physician is unable to address psychiatric symptoms and psychosocial issues

10.5140.001180.00986‐10Lack of specialized medical institutions

9.22

0.002390.0132

6‐13

When transitioning to adult medical care, co‐payment for medical expenses is required,
which is a significant financial burden

7.701

0.00552

0.02416‐14

Lack of adult medical institutions offering comprehensive care

15.58

0.00008

0.0022Abbreviation: FDR, false discovery rate.

trait anxiety” for each of the 83 questionnaire items. The false

trait anxiety” was the dependent variable. The FDR was used for multiple

discovery rate (FDR) was used for multiple statistical comparisons.

statistical comparisons.
All statistical analyses were conducted using IBM SPSS Statistics,
Version 27.

Analysis III: Confirmatory logistic regression analysis
accounting for confounding factors
RESULTS
Finally, to determine the relationship between the high trait anxiety andparental difficulties accounting for potential confounding factors,

Analysis I

binomial logistic regression analysis (forced entry method) was conductedwith each item that yielded statistical significance in Analysis II (19 items:

The results of multiple regression analysis showed that R was 0.610 and

Table 3), and parental age, parental gender, child's age, child's gender, andthe R2 was 0.372 (p = 0.001). Of the 24 variables, the following five werehousehold income were used as independent variables, and “#13: highsignificantly associated with parental psychological distress (K6 score):

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6 of 97 of 9T A B L E 4 Summary of binomial logistic regression analysis on relationship between high trait anxiety and each of the 19 items, parental age,parental gender, child's age, child's gender, and household income

Item #Item

OR

95% CI

Uncorrected p

FDRcorrected p

1. Perceived challenges in parent–child relationships
1‐2

Proximity with parents

4.067

1.496–11.060

0.006

0.023

1‐4

Defiance or opposition

8.241

2.246–30.245

0.001

0.009

4.434

1.497–13.127

0.007

0.023

2. Perceived challenges in medical care services
2‐6

Informing the individual of their diagnosis with 22q11.2
deletion syndrome

3. Perceived challenges in welfare services
3‐8Lack of knowledge on the part of supporters (welfare facility
personnel and government personnel) regarding 22q11.2
deletion syndrome

4.429

1.632–12.017

0.003

0.017

3‐9

No welfare facilities suitable for the characteristics and traitsof the individual with 22q11.2 deletion syndrome

7.463

2.621–21.250

0.0002

0.003

3‐18

Lack of help/support in daily life

6.017

1.564–23.144

0.009

0.024

14.1253.036–65.727

0.001

0.007

4. Perceived challenges in education services
4‐19Communicating with the home room teacher

Abbreviations: CI, confidence interval; FDR, false discovery rate; OR, odds ratio.

child's gender (β = −0.215, p = 0.018), hampered motor functions/skills

education services, coordination between these services, and the(β = 0.196, p = 0.047), high trait anxiety (β = 0.265, p = 0.018), inability toparent–child relationship.

join groups (β = −0.266, p = 0.013), and excitement/violence (β = 0. 252,

In terms of difficulties related to medical care services, thep = 0.013). These results confirmed that the characteristic of high anxiety

problem of disclosing their child's diagnosis of 22q11DS to the childof the children was significantly related to the difficulties that the family

was related to the anxiety characteristics of the children. It is possible

encountered in supporting them.

that parents are concerned about how the disclosure of the diagnosis
would distress their child with high trait anxiety levels. A previous
study conducting an online survey revealed that parents who haveAnalysis II

children with 22q11DS reported that the diagnosis experience wasnegative and often accompanied by a lack of support and appropriate

The χ2 tests for the 83 items indicated that 19 items showed ainformation.20 Moreover, in the parent–child relationship, the fact

statistical significance (FDR‐corrected p < 0.05) (Table 3).

that defiance and proximity with parents were statistically significant
in this study may be related to the difficulties associated with thedisclosure of 22q11DS diagnosis. Previous studies have reported that

Analysis III

parents were concerned about disclosing the diagnosis to the child,and they needed information on when, at what level, and how to

Finally, the binomial logistic regression analysis indicated that seven

disclose this.21 In Japan, there is a lack of genetic counselingitems showed statistical significance (FDR‐corrected p < 0.05) (Table 4).

specialists, and this issue needs to be addressed in the future.
In terms of difficulties related to welfare services, it wassuggested that there is a relationship between the individual's

DISCUSSION

adjustment to social life and anxiety characteristics, such as a lackof welfare facilities and workplace that match the individual's

To our knowledge, this study is the first to clarify quantitatively

characteristics and traits, and lack of help and support in daily life.

how high trait anxiety in 22q11DS is related to the parents'

In response to these situations, inadequate knowledge about

perceived difficulties in medical, welfare, and educational services.

22q11DS among the supporting services (welfare service staff,

Among the various characteristics of 22q11DS, we confirmed thatadministrative staff, etc.) may make it difficult to provide betterhigh trait anxiety was significantly associated with parental

support, thus creating a vicious circle between children's anxiety,psychological distress. Furthermore, high trait anxiety was associ-social maladjustment, and parent's distress due to perceived lack ofated with various difficulties encountered in medical care, welfare,appropriate support.

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HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME|HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME

In terms of difficulties related to education services, difficulty

CONCLUSION

in communication with the teacher in charge was observed. Thereis a possibility that teachers do not understand the severity ofThis study clarified the situations and circumstances in which

the child's anxiety as a medical characteristic and impose the

22q11DS individuals with severe trait anxiety and their caregivers

stereotype in the education of children with typical development

face difficulties. These results suggest the necessity of reconstructingor those with single disability (physical or intellectual) that theservice structures to more “anxiety‐informed” ones, where it issocial anxiety and fear should be overcome through school life.

important to provide person‐centered places and services that match

Cutler‐Landsman 22 suggested that the educational staff needs tothe characteristics and features of each individual, rather thanbe informed about the syndrome so they can understand the risk

conforming them to existing uniform services.

of too much pressure, for which our study may provide empirical
A UT H O R C O N T R I B U TI O NS

evidence.
In terms of difficulties related to the parent–child relationship,

Naomi Nakajima, Miho Tanaka, Akiko Kanehara, Ryo Morishima,

defiance and proximity with parents were significant. The

Yousuke Kumakura, Noriko Ohkouchi, Junko Hamada, Tomoko

mismatch between anxiety as a characteristic and the social

Ogawa, Hidetaka Tamune, Mutsumi Nakahara, Kayo Ichihashi,

environment and structure of medical care, welfare, education,

Seiichiro Jinde, Yukiko Kano, Kyoko Tanaka, Yoichiro Hirata, andand so forth designed for the majority of children may lead to

Kiyoto Kasai conceptualized and designed the study. Akiko

further avoidance, closer parent–child relationships, and rebel-

Kanehara, Ryo Morishima, Yousuke Kumakura, Junko Hamada,

22

Furthermore, previous

Ichiro Sakamoto, Kyoko Tanaka, Yoichiro Hirata, Hirofumi

research9 showed that adults with 22q11DS spend significantly

Ohashi, Tokuko Shinohara, and Kiyoto Kasai acquired the data.

more time with those closest to them than healthy controls, which

Naomi Nakajima, Miho Tanaka, Akiko Kanehara, Ryo Morishima,suggests that there is a high burden on the families of individuals

Shunsuke Mori, and Kiyoto Kasai analyzed the data. Naomi

with severe trait anxiety.

Nakajima and Kiyoto Kasai drafted the manuscript. All authors

lious attitudes within the family.

participated in result interpretation; moreover, they reviewed andapproved the final version of the manuscript.

Limitations
ACKNOWLEDGME NT SThis study has some methodological limitations. First, there is the

The authors would like to acknowledge the assistance of parents

issue of the representativeness of the target population.

caring for an individual with 22q11DS for a patient–publicInformation for the survey was disseminated through family

involvement process in creating the questionnaire. We would

associations and websites, and individuals presenting different

also like to thank the participants for responding to thedemographic and clinical characteristics responded from all overquestionnaire, and executive members of 22 HEART CLUB andJapan. However, since the author's group is the only one in Japan

the Association for the Protection of Children with Heart Disease

that operates a specialized psychiatric outpatient clinic forfor announcing this questionnaire to their members. We also

22q11DS patients, it is possible that individuals with greater

thank the healthcare and research professionals for theirdifficulties and needs than those with the standard syndrome

announcements. We thank Drs Shuntaro Ando, Masato Fukuda,

characteristics in Japan had participated in the study. Second, theYuki Miyamoto, and Sosei Yamaguchi for their helpful commentsinterviews were conducted with family members, and theto improve the questionnaire. Finally, we would like toanswers were mainly provided by mothers. Conducting inter-thank Editage (www.editage.com) for English‐language editing.

views and questionnaire surveys for individuals with 22q11DS on

This study was supported by JSPS KAKENHI (Grant Nos.

a large scale is difficult due to intellectual limitations and high

JP20H03596, JP21H05171, and JP21H05174), JST Moonshot

anxiety and tension in interpersonal situations; however, thisR&D (Grant No. JPMJMS2021), and by IRCN and UTIDAHM.

should be addressed in future investigations. Third, related to thesecond limitation, children's anxiety may reflect at least in part a

CONFLIC T OF INTEREST STATEM ENT

projection of their parents' anxiety, which should be carefully

The authors declare no conflict of interest.

considered when interpreting the results of our findings. Fourth,
our study was cross‐sectional and the causal relationship in the

DATA AVAILABILITY STATEMENT

strict sense was not clear. Finally, we did not assess the parental

The availability of the data in this study is not open access due

own diagnosis of 22q11DS, although unlikely being the case forto the provisions of the ethics committee and the extent ofmany, and thus could not control the potential effect of thethe participants' consent. If readers wish to apply for the use

possibility that parents and their child may share the challengesof data, they must contact the corresponding author and consult

and that parental stress may be elevated due to parents' own

the Ethics Committee, Faculty of Medicine, The University ofchallenges.

Tokyo.

27692558, 2023, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/pcn5.80 by Cochrane Japan, Wiley Online Library on [25/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

8 of 9

E T H I CS APP ROV AL S T A T E ME N T
This study was approved by the Ethics Committee of the Faculty of
Medicine, The University of Tokyo (approval No. 2018015NI). The

11.

participants expressed theirconsent to participate in the study by
responding to the questionnaires.
12.

PA TI E NT CO N S EN T S T A T EME NT
The participants expressed their consent to participate in the study

13.

by responding to the questionnaires.
CLINICAL TRIAL REGISTRATION
N/A

14.

ORCID
Naomi Nakajima

http://orcid.org/0000-0002-5215-5878

Yukiko Kano

http://orcid.org/0000-0002-2341-5095

Kiyoto Kasai

http://orcid.org/0000-0002-4443-4535

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How to cite this article: Nakajima N, Tanaka M, Kanehara A,
Morishima R, Kumakura Y, Ohkouchi N, et al. Relationshipbetween high trait anxiety in 22q11.2 deletion syndrome andthe difficulties in medical, welfare, and educational services.
Psychiatry Clin Neurosci Rep. 2023;2:e80.
https://doi.org/10.1002/pcn5.8027692558, 2023, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/pcn5.80 by Cochrane Japan, Wiley Online Library on [25/05/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License|

HIGH TRAIT ANXIETY IN 22Q11.2 DELETION SYNDROME