Participants
This study used data from the Tokyo Teen Cohort (TTC) study (http://ttcp.umin.jp/), a population-based longitudinal survey focusing on children’s health from biopsychosocial multidisciplinary viewpoints (26). The TTC study has started from October 2012 and is currently being conducted. The participants were recruited from three municipalities in Tokyo (Setagaya, Mitaka, and Chofu) using the Basic Resident Register. The candidate participants were 14,553 children born between September 1, 2002, and August 31, 2004. Invitation letters were sent to the primary parents of those children around their tenth birthday. Of these children, 10,234 were successfully contacted, and these children were invited to participate in the cohort study. Of these 10,234 children, 4,478 children participated in the baseline survey named the Tokyo Early Adolescence Survey (T-EAS). This baseline survey was conducted from October 2012 to January 2015, when the participants were approximately 10 years old (time 1, T1). Among the 4,478 participants in the T-EAS, candidates were chosen as participants for the second wave of the TTC study. For the sake of cohort management, the target number of participants to be included in the second wave of the TTC was 3,000 children. When choosing these TTC participants, an oversampling method was used instead of inclusion criteria, considering the low follow-up rate of families with low annual household incomes. Thus, 3,171 participants were extracted as targets for the second wave of the TTC study. This second wave of the TTC study was carried out from August 2014 to December 2016, at the time when the participants were approximately 12 years old (time 2, T2). Of the 3,171 children who were invited, 3,007 individuals participated in the second wave of the TTC study (follow-up rate 94.8%). In each wave of the data collection, trained interviewers visited the participants’ homes. They distributed questionnaires to the children and primary parents (mostly mothers), and they conducted psychological tests on the children.
Ethical approval
Ethical approval for this study was obtained from the research ethics committees of the Tokyo Metropolitan Institute of Medical Science (Approval number: 12-35), The Graduate University for Advanced Studies, SOKENDAI (2012002), and the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo (10057). We obtained informed assent from the children and written informed consent from their primary parents.
Measures
Tics
We evaluated tics at T1 and T2. The participants’ primary parents answered a questionnaire about the children’s tics; this questionnaire has been used in a previous study (5). The questionnaire includes a section with the following five questions about specific motor and vocal tics in the past year: “Q1: Has your child had any repeated movements of parts of the face and head (e.g., eye blinking, grimacing, sticking tongue out, licking lips, spitting)?”; “Q2: Has your child had repeated movements of the neck, shoulder or trunk (e.g., twisting around, shoulder shrugging, bending over, nodding)?”; “Q3: Has your child had repeated movements of the arms, hands, legs, or feet?”; “Q4: Has your child had repeated noises and sounds (e.g., coughing, clearing throat, grunting, gurgling, hissing)?”; and “Q5: "Has your child had repeated words or phrases?” Each question is answered as either “definitely”, “probably” or “not at all” present. Furthermore, we asked the following question about the frequency of these repetitive behaviors: "Q6: About how often does/did this happen in the last year?" This question was answered on the following 5-point Likert scale: “1: less than once a month, 2: 1-3 times a month, 3: about once a week, 4: more than once a week, 5: every day.”
We evaluated the presence of tics using binary variables consisting of either “with tics” or “without tics.” We defined the participants who responded “definitely” or “probably” to any of Q1, Q2, and Q4 as having tics. The participants who only endorsed repeated movements of the arms, hands, legs or feet (Q3) or repeated words or phrases (Q5) in the absence of a positive response to the other questions about the types of tics (Q1, Q2, Q4) were excluded from all case definitions to remove nontic movements such as stereotypy or isolated echolalia. We defined as tics all responses of “definitely” or “probably” to questions concerning motor and/or vocal tics regardless of their frequency because there is no condition of frequency in the diagnostic criteria of tic disorders (1) and because we aimed to exhaustively find tics in the general population.
In the post hoc analysis, we used a narrower definition of tics that required answers of “definitely” or “probably” to questions concerning motor and/or vocal tics and frequencies of “daily” or “more than once a week.” This narrower definition of tics referred to the “broad definition of TS and CT” used in a previous population-based study investigating the prevalence of TS/CT (5). The “broad definition of TS and CT” used in this previous study differed from the narrower definition of tics used in this study in that the previous study was carried out on participants aged 13 and excluded subjects with an intellectual disability or autism.
Maternal depressive/anxious symptoms
We employed the Kessler Psychological Distress Scale (K6) (27-29) for T1 and the General Health Questionnaire-28 (GHQ-28) (30, 31) for T2. The K6 and the GHQ-28 are both widely used self-report questionnaires that were developed to evaluate depressive/anxious symptoms. We used different scales between T1 and T2 in the current study because the TTC study also switched the scale used for maternal depressive/anxious symptoms from the K6 to the GHQ-28 starting at T2. The K6 is a short questionnaire consisting of 6 questions about the subjective mental distress of the respondent over the past 30 days that are answered on a 5-point scale, and the scores of the 6 items are added together (0-24 points). The GHQ-28 consists of 28 questions about the respondent’s subjective physical and mental states over the past few weeks, with a total score being calculated for each item by giving 0 points each for the right two responses and 1 point each for the left two responses (0-28 points). Cutoff values are often used to screen for anxiety disorders and depression when assessing the K6 and the GHQ-28. However, in this study, we used raw values of the K6 and the GHQ-28 as continuous scales instead of screening scales, for the purpose of evaluating the severity of depressive/anxious symptoms, including the normal range in the general population. The Cronbach’s alpha value was .84 for the K6 and .88 for the GHQ-28. We found that the distributions of the K6 and the GHQ-28 were similar based on the graphing cumulative distribution of their Z scores (Figure 1). If a primary parent other than a mother answered the K6 or the GHQ-28, we regarded those responses as missing values.
Other variables
Sex (5, 7, 32), age (33-35), maternal age (23, 36-38), socioeconomic status (39), and maternal alcohol use during pregnancy (40) were included in the analyses since previous studies have reported that these factors influence the occurrence of TS/CT. The data for these variables were obtained from the responses to the questionnaires completed by caregivers. To assess socioeconomic status, family income was evaluated on a 10-point scale, which ranged from "0-990,000 yen” to “more than 10,000,000 yen.” Information on maternal alcohol use during pregnancy was obtained from maternity record books that were provided for almost all mothers by local public organizations in Japan.
Statistical analysis
Longitudinal relationships between maternal depressive/anxious symptoms and children’s tics were studied with structural equation modeling. We used SPSS® (Statistical Package for Social Science; IBM Corp., Armonk, N.Y. USA) version 21.0 for the characteristics of the study participants and Amos ver. 22.0 (IBM Corp, New York) for the structural equation modeling. We used the following three cross-lagged design models. The first model analyzed the longitudinal relationships between maternal depressive/anxious symptoms and children’s tics without adjusting for covariates (unadjusted model). The second model adjusted for sex, age in months, family income, maternal age, and maternal alcohol use during pregnancy (adjusted model). Finally, the third model took into account the nonnormal distribution of particular dependent variables (maternal depressive/anxious symptoms and children’s tics at T2), logarithmically converted these measures and then conducted an analysis (logarithmically transformed model).
We also conducted a post hoc analysis by using the narrower definition of tics, which referred to the “broad definition of TS and CT” used in a previous study about the prevalence of TS/CT (5). The aims of the post hoc analysis were to compare the prevalence of tics in this study with that from the previous study and to examine the stability of the results on the relationships between maternal depressive/anxious symptoms and children’s tics.
Missing values in the categories of tics, maternal depressive/anxious symptoms, and the covariates were accounted for by full information maximum likelihood procedures available in Amos. This method estimates model parameters and standard errors using all available data while adjusting for the uncertainty associated with missing data (41).
The threshold for statistical significance was set to p < .05 (two-sided) for all analyses. We evaluated the fit of our models by using the comparative fit index (CFI) and the root mean square error of approximation (RMSEA). A good model fit was indicated by an RMSEA value smaller than .05 and a CFI value larger than .95 (42, 43).