International Journal of Epidemiology, 2019, 1–8
doi: 10.1093/ije/dyz033
Cohort Profile

Cohort Profile: The Tokyo Teen Cohort study(TTC)
Shuntaro Ando,1,2*† Atsushi Nishida,2† Syudo Yamasaki,2
Shinsuke Koike,3,4 Yuko Morimoto,2 Aya Hoshino,2 Sho Kanata,5Shinya Fujikawa,1 Kaori Endo,2 Satoshi Usami,6 Toshiaki A Furukawa,7,8
Mariko Hiraiwa-Hasegawa9 and Kiyoto Kasai;1,4 TTC Scientific and Data
Collection Team1

Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan,
Department of Psychiatry and Behavioral Science, Tokyo Metropolitan Institute of Medical Science,
Tokyo, Japan, 3University of Tokyo Institute for Diversity and Adaptation of Human Mind (UTIDAHM),
University of Tokyo, Tokyo, Japan, 4The International Research Center for Neurointelligence (WPI-IRCN),
University of Tokyo Institutes for Advanced Study (UTIAS), Tokyo, Japan, 5Department of Psychiatry,
Teikyo University School of Medicine, Tokyo, Japan, 6Center for Research and Development on Transition
from Secondary to Higher Education, University of Tokyo, Tokyo, Japan, 7Department of Health Promotionand Human Behavior, 8Department of Clinical Epidemiology, Kyoto University, Kyoto, Japan and 9School of
Advanced Science, SOKENDAI (Graduate University for Advanced Studies), Kanagawa, Japan
2*Corresponding author. Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
E-mail: sandou-tky@umin.ac.jp†
These authors contributed equally to this work.
Editorial decision 13 February 2019; Accepted 26 February 2019

Why was the cohort set up?
Adolescence is the phase of life stretching between childhood and adulthood, for which a definition of 10–24 years
has been recently proposed.1 Adolescence is a critical phasein life when an individual acquires the physical, cognitive,
emotional, social and economic resources that are thefoundation for health and well-being in later life.2 With regard to physical change, adolescence is characterized bydynamic brain development and drastic physical change
owing to puberty.3,4 Especially, gradual maturation of prefrontal cortical function during adolescence enables
higher-order mental processes including self-regulation.5
Humans can use this ability to regulate their own mind,
and consciously and recursively develop themselves.
Other than dramatic physical change, environmental
factors contribute to the social construct of adolescence asa distinct period of life, including the rise in education andsocial media exposure.6 Historically, since the pubertal
timing has moved ahead but social role expectancy for
adulthood has moved backward in recent years, mismatchof physical and mental maturity may likely occur in adolescence in the present day.7 The mismatch and an inappropriate maturation of self-regulation in adolescence could
lead to the increased incidence of mental health problems
among adolescents in modern society.8
Among health problems during adolescence, mental
and substance use disorders are the leading cause of years
lived with disability (YLDs),9 and approximately threequarters of people with mental disorders have their onset
before the age of 18.10 Further, in many countries including Japan, suicide is one of the leading causes of death inyoung people in recent years.11 Since brain change occurs

C The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.
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Cohort Profile2

Who is in the cohort?
TTC is a multidisciplinary longitudinal cohort study. The
study is conducted at three municipalities in metropolitan
area of Tokyo, Japan. The sample was recruited from theparticipants in the Tokyo Early Adolescence Survey (TEAS),12 which was a cross-sectional survey on psychological and physical development of general adolescents
10 years old, and data from T-EAS were treated as the firstwave of data for the TTC. Participants of T-EAS wererecruited between October 2012 and January 2015. A
broad range of adolescents from a wide geographical area,
extending 9598 m2 in three municipalities (Setagaya-ku,
Mitaka-shi, Chofu-shi) in the metropolitan area of Tokyo,
were recruited into T-EAS (Figure 1). Children who lived
in the municipalities and were born between September
2002 and August 2004 were recruited from the area using
the resident register in each municipality. Among 18 830
eligible children, 14 553 children were randomly chosen
due to a limited research budget (Figure 2). An invitation

Figure 1. Catchment area of TTC.

Eligible children (n=18830)

Randomly selected sample (n=14553)

Accessible sample for T-EAS (n=10234)

Not contacted (n=4319)
Moved(n=1364)
Address unidentified (n=293)
Long-term absence (n=101)
Inaccessible contact (n=2561)
Refusal (n=5756)

Participants in T-EAS (n=4478)

Selected for TTC wave 1 (n=3171)

Participants in TTC wave 2 (n=3007)

Figure 2. Flowchart of participant recruitment in TTC.

letter to T-EAS was sent approximately when participants
turned 10 years old, and a trained interviewer visited theirhome after the letter was sent. The child’s primary parent(usually mother) gave written informed consent. Of 14 553
children, 4319 children could not be contacted. Of the
10 234 children who were accessible, 4478 children agreed
to participate in T-EAS (response rate: 43.8%). The female
ratio was lower in responders compared with nonresponders (46.9% vs 49.8%, /¼0.03, p <0.01), and responders were less likely to be resident in Setagaya-ku andmore likely to live in Mitaka-shi (Setagaya-ku: 62.6% vs68.3%, Mitaka-shi: 18.3% vs 12.7%, V ¼ 0.08, p <0.01),
but there was no difference in birth month between participants and non-participants in T-EAS.
Candidate participants of TTC were chosen from 4478
children who participated in T-EAS. A total of 3000 children was the target number of participants in the second
wave of TTC. When choosing the participants of TTC, no
inclusion criteria were applied, but an oversampling
method was used considering low follow-up rate of families with low annual household income. Among children
who participated in T-EAS and had interest in participating in the cohort study, all 620 children whose household
annual income was lower than 4990 thousand yen were invited. From the rest of 3858 children, 2551 children were

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during adolescence including the areas related to cognition,
self-regulation and judgement,7 it may be reasonable tospeculate that inappropriate brain maturation could leadto the emergence of mental disorders.5 Such brain andphysical development occurs associated with both biological (genetics, epigenetics, natural endowments) and environmental (national and local policies, as well as
community, school, workplace, peers, neighbourhood andfamily influences) factors. Thus, a life course approachwith a multidisciplinary viewpoint is required to understand adolescent trajectories.6
Despite the importance of adolescence in the life course,
few cohort studies have examined adolescent developmentusing a prospective design. Physiological and psychologicaldevelopmental processes during adolescence, factors
affecting the process and interaction between them have notbeen sufficiently revealed. Our study, the Tokyo Teen
Cohort study (TTC), is a prospective population-based birthcohort study aimed at investigating physiological and psychological development, including self-regulation, duringadolescence. This multidisciplinary study collects data fromvarious sources (parent, child, interviewer) via multiple
methods (maternity record, self-report, interview, neurocognitive tests, biological measures and neuroimaging). Alongwith this main cohort study, a subsample study focusing on
neuroimaging was also launched. The subsample study(population neuroscience TTC: pn-TTC) has conducted
brain magnetic resonance imaging of children longitudinallyand investigated the neurodevelopment of general adolescents. Given the focus of our project, early adolescence wasan appropriate timing for the baseline survey.

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3

Table 1. Demographic characteristics of participants in TTC(N ¼ 3171)
%/SD

1487
1684
122.10
3117
2978

53.1%
46.9%
3.30
98.3%
93.9%

1999
574
598
160

63.0%
18.1%
18.9%
5.0%

524
1391
1126
105

16.5%
43.9%
35.5%
3.3%

542
409
1692
374

17.1%
12.9%
53.4%
11.8%

142
763
1224
917
1.14
4.20

4.5%
24.1%
38.6%
28.9%
0.79
0.95

Sample maintenanceTo maintain the attrition rate low, we have actively sought
to retain the interest and compliance of the young sample inour cohort. We maintain contact with participating families
via customized birthday cards, a semi-annual newsletter,‘change of address’ postcards and ‘thank you’ cards for theparticipants. Parents were asked to provide contact details
that will be used for tracing participants at future waves ifnecessary. The TTC website [http://ttcp.umin.jp/], on which
we post commentaries, research members and selected observations, will serve as a repository for reporting findings.

What has been measured?
randomly invited to the second wave of TTC.
Demographic characteristics of the participants of TTC areshown in Table 1.
TTC is based at three research institutes: Tokyo
Metropolitan Institute of Medical Science, the Universityof Tokyo and SOKENDAI (Graduate University for
Advanced Studies). Ethics approval has been granted by allof the three institutions.

How often have they been followed up?
Data collection every 2 years is currently planned. The firstwave of data collection took place between 2012 and2015, and the second wave took place between 2014 and2017. The third wave of data collection has started fromMarch 2017 and is currently being conducted. Of the 3171
children who were invited, 3007 individuals participatedin the second wave of TTC (follow-up rate 94.8%). When
comparing those who were followed up and who were lost
to follow-up, there were no differences in demographic
characteristics including age (mean 122.1 months vsTable 2 presents a summary of measures and the waves atwhich they were collected. This paper describes wave 1 indetail, noting any changes in later waves. Data were collected at home from the child and a primary parent (usually mother) by both interview and self-reportquestionnaires. There were two sets of questionnaires (part1 and part 2) for both child and a parent. Trained interviewers visited the participant’s home twice to collect data.
Many children had the same interviewer for each of the
waves, but some children had different interviewers for theseries of waves. For example, 63.1% of children had thesame interviewer for wave 1 and wave 2. At the first visit,
written informed consent was obtained and part 1 selfreport questionnaires were distributed to child and a parent. The questionnaire usually takes about approximately
25 to 35 min for children and 20 to 40 min for parents tocomplete. Then, at the second visit, anthropometric measurement was completed for child, and part 2 self-reportquestionnaires were distributed to child and a parent. The
part 2 questionnaire was distributed along with an envelope to seal it in when completed, in order for participants

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Sex
FemaleMale
Age (months)
Mother’s country of origin (Japan)
Father’s country of origin (Japan)
RegionSetagaya
MitakaChofu
Single parent
Educational level of motherHigh school or less2-year college
4-year university
Graduate university
Educational level of father
High school or less2-year college
4-year university
Graduate university
Annual household income 10 000 yen)
0-299
300-599
600-999
1000þ
Number of siblings
Number of people in household

Number/mean

122.0 months, p ¼ 0.61), sex (female ratio 47.2% vs42.1%, p ¼ 0.20), number of siblings (mean 1.14 vs 1.12,
p ¼ 0.80), paternal education (mean 4.60 vs 4.62, p ¼
0.79) or maternal education (mean 4.25 vs 4.20, p ¼ 0.51).
In wave 1, a self-report questionnaire was administered andphysical examination and interview at home were conducted with both children and parents by the interviewers.
A similar method was applied to collect data by the interviewers in wave 2. In addition, a touch-panel device (iPad,Apple Inc., USA) was used to measure some aspects of cognitive function of children and parents in wave 2. In wave
3, similar to wave 1, both self-report questionnaire and interview were used to collect data. Along with TTC, the subsample study pn-TTC has also been conducted. The detailsof the pn-TTC are described elsewhere.13

4International Journal of Epidemiology, 2019, Vol. 0, No. 0

Table 2. Measures and time points in TTC
MethodConstructPsychological wellbeing
Psychological development, Character

Personal relationships

Academic achievement
Physical health, nutrition and otherproblems

Pubertal development
Life event
Environment
ParentingParent healthParental mental healthParental cognitive
function
Social support for parent, demographics

1(10 years)2(12 yreas)3(14 years)

Interviewer
ParentParent
Child
Child













CNSIE, MCQ, CPAQ,
sensation-seeking
Personalized values,
aspirations
Bullying, help-seeking,romantic relationship,
family relationship
Performance in school
Special health care needs,
medication, sleep habit
Extracurricular activity
Internet addiction
Cellphone use, TV viewing
Tanner stage, physical change
Separation from parents,
bereavement
School environment, private
school use, neighbourhood
Style of parenting
Medication, smoking, alcohol
use
K6, GHQ, purpose in life
JART

Child





Parent/child







Parent/child







ParentParent










Parent/child
ParentParentParent/child
Parent
















Parent/child







Parent










ParentParentParent











Interviewer
Interviewer
iPad
Child
Child








Anthropometricmeasurement

Anthropometry

Interview
iPad
Saliva sampling
Urine sampling

Cognitive function
Inhibition, risk taking
DNA, hormones etc.
Trace element etc.

Length of finger
WISC-IIIGo No-go task, BART
DNA, hormone etc.
Trace element etc.

Prenatal and postnatal
factors

Wave (age of participants in years)

Self-organization
SDQ, CBCL
TIC
SMFQ, APSS
WHO-5

SSQ, family composition,
parental age, national
origin, education, work,
annual household income
Gestational age, medical
condition during pregnancy,
smoking, alcohol use, modeof delivery, anthropometryat birth
Breastfeeding
Anthropometry during infancy
Developmental milestones
Nursery use
Height, weight, grip

Maternity record

SourceMaternity record Maternity record Maternity record Maternity record ParentInterviewerDownloaded from https://academic.oup.com/ije/advance-article-abstract/doi/10.1093/ije/dyz033/5382248 by Rinshoken user on 31 March 2019

Self-report questionnaire Mental health and behaviour problems

MeasuresInternational Journal of Epidemiology, 2019, Vol. 0, No. 0

friends, help-seeking for depression, and romantic relationship were also asked. Further, by asking both children andparents, we assessed family relationships including conversation, weekends and help with homework.
Since individuals’ hierarchies of values stabilize duringadolescence,26 we assessed the personalized values and future aspirations of adolescents using free-writing questions
and original questionnaires. Further, because the development of the individual’s values are affected by social andfamily environment,26,27 we also assessed the personalized
values of primary parents and their aspirations for theirchildren’s future, to examine the trans-generational shapeof values and behaviours.

Children’s psychological development/health
Psychological development was evaluated from several aspects.
Locus of control (the extent to which one perceives a causal
connection between one’s behaviour or cognition and subsequent outcomes) was measured by the short form of theChildren’s Nowicki-Strickland Internal-External Scale(CNSIE).14 In order to evaluate how children assessthe futureconsequences of their actions, a delay-discount rate wasassessed using the Monetary Choice Questionnaire (MCQ).15
The Childhood Personality Attribute Questionnaire (CPAQ)
was utsed to assess psychological masculinity and femininity.16
In addition, questions about sensation-seeking, empathy, attitude to helping others and sense of time were also asked.
Self-organization was one of the focuses of psychological development of the children. The assessment of selforganization was started after the initial 1500 interviews
were completed. Children’s self-organization was assessedby interviewer comparing the child with other children
they had seen. Four items were used for assessment including attitude to work, concentration, neatness in work anddaydreaming during the home visit.17
Mental health and behavioural problems were also major focuses of this study. Those measurements included theStrength and Difficulties Questionnaire (SDQ),18 the Child
Behavior Checklist (CBCL),19 the Short Mood andFeelings Questionnaire (SMFQ)20 and the Japanese versionof the Adolescent Psychotic-Like Symptom Screener(APSS)21 which is composed of seven items selected fromthe Diagnostic Interview Schedule for Children (DISC),22
corresponding to psychotic symptoms including hallucination and delusion.23 Psychological well-being was measured by the WHO-Five Well-Being Index (WHO-5).24
In terms of personal relationships, bullying involvement
was assessed using self-report questions according to thedefinition of bullying defined in the Olweus Bully/Victims
Questionnaire (OBQ).25 In addition to the report fromchildren, main carers were separately asked about bullying
involvement of their children. Leadership, quarrels withChildren’s cognitive development
Two subtests (information, picture completion) were selected from the Wechsler Intelligence Scale for Children(WISC-III) to test cognitive function of children, referring to
the short form of the WISC-III in the previous study.28 We
gave full version of the WISC-III by expert psychologists to
28 children from T-EAS participants after 1 year from theinitial survey. There was acceptable reliability of measurements of Intelligence and Picture Completion (Cronbach’s a¼ 0.70 and 0.54, respectively). Considering the result fromthe multiple regression analysis with full IQ as dependent
variable and the two subtests as independent variables (adjusted R2 ¼ 0.78), we developed a formula for estimating
children’s IQ from the two subtests. In addition to the
WISC-III, the Go No-go task29 and the Balloon Analogue
Risk Test30 were conducted using iPad in wave 2. In addition, primary parents evaluated children’s academic performance at school using a five-point Likert scale for eachacademic subject. In Japan, all public elementary schools issue a report card for each student, evaluating achievementin each subject by the same standards in the absolute scale(‘Satisfactory’, ‘Almost satisfactory’, ‘More efforts needed’).

Children’s physical development/health
Height, weight, grip and length of forefinger and third fingerof the child were measured at home by a specially trained interviewer. Pubertal development was evaluated by both a childand a primary parent. A primary parent assessed the children’s
pubertal development by choosing pictures of bodies according to the Tanner stage (breast and pubertal hair for girls, andgenital development and pubertal hair for boys).31,32 Apartfrom evaluation by a primary parent, children evaluated themselves on acne, pubertal hair, breast (female), menarche (female), voice breaking (male) and beard (male).
With regard to physical health, needs of special healthcare was also evaluated by a primary parent.33 In terms of

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to be able to answer without being seen by other family
members. Those were collected by the interviewers immediately after completion. Further, an interviewer conducteda structured interview for both the child and a parent. The
structured interview was conducted for child and parent
separately, and they were not present for each other’s interview. The interview for the child included cognitive tests.
Further, an interviewer answered a short questionnaire on
the child’s character/behaviours after home visits werecompleted. In wave 2, iPad application was used to administer cognitive tests, and saliva and urine samples were collected after interview.

5

6Perinatal environment
Perinatal information was gathered from the Maternal andChild Health handbook which is distributed to all pregnant mothers in Japan.35 Pregnant women in Japan bring
the book to health check-ups during pregnancy and afterchildbirth. The recorded data included mother’s anthropometry, smoking, drinking during pregnancy, fetal
growth, mode of delivery, breastfeeding, birthweight,
growth in infancy and developmental milestones. Use ofnursery and working status of parents during childhood
were also assessed in the self-report questionnaire.

Household environment
Number of siblings in the household was asked in the interview of the primary parent conducted at a home visit.
Marital status of parents, educational level of parents andannual household income were assessed by the self-reportquestionnaire. Information on the parent focused on physical and mental health of parents, which included parental
psychological distress assessed by K6,36 and purpose inlife.37 Parental cognitive function was evaluated using the25-item Japanese version of the National Adult Reading
Test (JART).38,39 Social support for the parent wasassessed using a six-item instrument of the Social Support
Questionnaire (SSQ6).40,41

What has been found so far? Key findings
and publications
More than 10 manuscripts are currently submitted or in
preparation for publication. A complete list of publications

will be available on the TTC website [http://ttcp.umin.jp/
publications.html]. Some of the findings from TTC relate
to psychological mechanisms indicating the association between the children’s experiences and psychological health.
One study examined the association between experience ofbeing bullied, dissociation and hallucinatory experiences.
This study suggested that dissociation was a mediator in
the relation between peer victimization and hallucinatory
experiences in early adolescence.12 Another study investigated the association between enuresis and behaviouralproblems of early adolescents. This study revealed that enuresis was independently associated with hyperactivityinattention among the general population as measured by
the Strength and Difficulties Questionnaire.42 Helpseeking intention was also a focus of TTC, and a study
examined the factors and sex difference in help-seeking intention in early adolescents. The study revealed that girls
had more help-seeking intention for depression than boys.
Further, this study also investigated factors associated withhelp-seeking intention, and gender norms inhibited helpseeking intention more strongly in boys than in girls.43
Some of our studies focused on physical and psychologicalhealth of mothers of adolescents. A study examined the association between purpose in life and tobacco use of mothers, and revealed that greater purpose in life was associatedwith a decreased likelihood of tobacco use.44

What are the main strengths andweaknesses?
One of the main strengths of TTC is its prospective research design and the multidisciplinary nature of the data.
The prospective design enables analyses of changes overtime, and the multidisciplinary nature of the data enables
more in-depth understanding of the physical and psychological development including self-regulation. Second,measurements uncommonly done in other large cohort
studies, such as saliva and urine sampling, facilitates analysis of biological factors affecting physical and psychological development. Third, an international advisory board
has also been established. The board consists of international experts in a multidisciplinary field of science including epidemiology, neuroscience and social science. There isa possibility of a cross-cohort study in the future in collaboration with the advisory board. Fourth, the follow-up
rate is as high as 94.8% in the second wave. This highfollow-up rate would enhance the generalizability of theresults from our cohort study. Fifth, since most participants have the same ethnic origin, investigation of biological factors in the homogeneous group can be conducted.
The weaknesses of TTC include the timing of start ofthe cohort study. Since TTC started at 10 years age, some

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life habit, appetite, sleep habit, dietary habit, extracurricular activities including music, painting, exercise and reading were asked. Further, addictive use of internet wasassessed using questions used in the previous study.34
For the purpose of further biological investigation, inwave 2, saliva and urine samples were collected from allparticipants in TTC. Measurements including sex hormones and oxidative stress have been planned. In wave 3,
urine samples were collected from all participants in TTC.
Further, we selected a subsample from TTC and conducted a prospective biological examination focusing on
population neuroscience in a longitudinal design (pnTTC). The examination includes neuroimaging using brain
magnetic resonance imaging (MRI) as well as saliva
sampling (DNA and gonadal and adrenal hormones).
We recruited about 300 children into the subsample study.
The subsample cohort study was initiated about 1 year after TTC, and has been carried out in parallel with TTC.

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Can I get hold of the data? Where can I findout more?
Data from TTC is archived in the Tokyo Metropolitan
Institute of Medical Science. Collaboration in data analysis
and publication will be welcome through specific research
proposals sent to the research committee. The initial
contact point for collaborations is [nishida-at@igakuken.
or.jp].

Profile in a nutshell• TTC is a transgenerational prospective population-

based birth cohort study aimed at investigating
physiological and psychological development, including self-regulation and personalized values, during adolescence.
• TTC was launched in 2012, and 3171 10-year-old

children were recruited from 4478 children who participated in a cross-sectional survey (T-EAS). Of
10 234 children who lived in the three municipalities
in Tokyo and were born between September 2002
and August 2004, 4478 children participated in TEAS.
• Follow-up has been conducted every 2 years. Data

collection was conducted by self-report questionnaire and interview for both children and primaryparent, and urine and saliva were also collected.
Along with TTC, a subsample study focusing on neuroimaging (pn-TTC) has also been conducted.
• The dataset comprises a wide range of multidiscipli-narymeasurement

includingthebiological,

cognitive, psychological and physical developmentof children. Also, perinatal, family and school environments were measured.
• Collaboration in data analysis and publication will bewelcome through specific research proposals sent to
the research committee. The initial contact point forcollaborations is [nishida-at@igakuken.or.jp].

Funding
This work was supported by Grant-in-Aid for Scientific Research on
Innovative Areas (23118002; Adolescent Mind & Self-Regulation)from the Ministry of Education, Culture, Sports, Science andTechnology of Japan. This study was also supported by JSPS
KAKENHI Grant Numbers JP16HY06395, 16H06398, 16H06399,
16K21720, 16K15566, and 17H05931. This work was supported inpart by UTokyo Center for Integrative Science of Human Behavior(CiSHuB) and by the International Research Center for
Neurointelligence (WPI-IRCN) at the University of Tokyo Institutes
for Advanced Study (UTIAS).
Conflict of interest: None declared.

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information on infancy and childhood may suffer from recall bias. However, because the Maternal and Child
Health handbook is distributed to all pregnant mothers inJapan, this may substantially cover the limitation. Since
the sample of TTC was recruited from a small number ofmetropolitan municipalities in Tokyo, social backgroundof TTC participants may not fully represent all residents inTokyo. In order to overcome this limitation, we have done
oversampling of participants in a survey (T-EAS) to recruit
samples of TTC. Since the participation rate in T-EAS(18 830 eligible children, 4478 participants ¼ 23.8%) was
low; there is a certain limitation about the representativeness of the study sample. Because most participants havethe same ethnic origin, caution is needed when expanding
the study results into other ethnic groups. Although we
gave the same training for interviewers beforehand, we did
not measure inter-rater variability for assessing selforganization of children.

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