Participants
The IMAGEN study is a multi-site multi-national longitudinal research project that includes data on 2462 14-year-old adolescents and their parents. Participants were recruited through high schools in eight European sites across the United Kingdom, Ireland, France, and Germany. Clinical and behavioral data were collected at baseline, and assessments were repeated at 2 (age 16) and 4 years (age 18) follow-up. A detailed description of recruitment and research procedures has been published elsewhere [30]. The study protocol was approved by the King’s College London (KCL) College Research Ethics Committee CREC/06/07-71 and each study site was granted approval from the local research ethics committee. Written consent was obtained from each participant and his or her guardian.
Instruments
Social preference and rigidity
To assess autistic traits in the IMAGEN population, items were derived from the following scales designed to capture personality traits and behavior in non-clinical populations:
The Neuroticism, Extraversion, Openness Personality Five Factor Inventory (NEO-FFI) [31] contains 60 questions on separate personality traits organized by the five-factor model (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness). The items are measured on a five-point Likert scale ranging from ‘strongly agree’ to ‘strongly disagree’. We selected three items from this scale: ‘I like to have a lot of people around me’, ‘I usually prefer to do things alone’ and ‘I really enjoy talking to people’.
The Temperament and Character Inventory Questionnaire (TCI) [32] is a self-report instrument that assesses four temperament (novelty seeking, harm avoidance, reward dependence, and persistence) and three character (self-directness, cooperativeness and self-transcendence) dimensions. It comprises 240 items rated on a five-point Likert scale, ranging from ‘definitely true’ to ‘definitely false’. Two item were selected from the TCI: ‘I hate to change the way I do things, even if many people tell me there is a new and better way to do it’ and ‘I like to pay close attention to details in everything I do’.
The Strengths and Difficulties Questionnaire (SDQ) [33, 34] assesses peer relations, conduct problems, emotional problems, prosocial behaviors and hyperactivity using 25 items on a 3- point Likert scale, ranging from ‘true’ to ‘not true’. From this scale we selected two items: ‘I have one good friend or more’ and ‘I am nervous in new situations. I easily lose confidence’.
When necessary, item scores were reversed, so that for each item a higher score represented more severe traits (Table 1).
Table 1 Selected questions on autistic traits ASD and ADHD diagnoses
IMAGEN is a general cohort study, which means participants with a clinical diagnosis of ASD or ADHD were excluded. However, some participants may still have met the diagnostic criteria for ASD or ADHD. We used the Development and Well-being Assessment (DAWBA) to identify and exclude these individuals from analyses. The DAWBA includes a package of interviews, questionnaires and rating techniques designed to diagnose psychiatric problems in 2–17 year-olds. Clinical raters use responses from informants to assign ICD-10 and DSM-IV psychiatric diagnoses. These clinician-rated DAWBA diagnoses are considered reliable and are able to discriminate well between community and clinical samples and between different diagnoses [35].
Alcohol use
To measure alcohol use, we used a short version of the Alcohol Use Disorder Identification Test (AUDIT), called the AUDIT-Consumption (AUDIT-C [36]). The items were designed to measure (1) frequency of alcohol use (How often do you have a drink containing alcohol?), (2) the amount of alcohol used (How many standard drinks containing alcohol do you have on a typical day when drinking?), and (3) the frequency of binge drinking (How often do you have six or more drinks on one occasion?). The AUDIT-C is a reliable measure of hazardous alcohol use [36] and has been validated in adolescent populations [37]. Questions are rated on a five-point Likert scale, ranging from 0 to 4 with higher scores indicating more frequent and more severe alcohol use (Table S1). The cut-off scores for alcohol use disorder in adults are ≥ 3 (women) or ≥ 4 (men) [36]. For adolescents, an item sum score of 2 or higher has been considered ‘problematic alcohol use’ [37].
Intelligence Quotient (IQ)
IQ was estimated with the WISC-IV subtests Vocabulary (crystalized IQ marker) and Matrix Reasoning (fluid IQ marker) [38, 39]. See supplemental Table S2 for a description of the WISC-IV.
Statistical analyses
Preparatory analyses
Item selection to measure autistic traits was performed using a stepwise approach. First, we evaluated all items from the SDQ, NEO-FFI, and TCI, using the DSM-IV ASD classification as reference [40]. This resulted in 18 potentially relevant questions. Second, we ran a principle component analysis to explore which items loaded best on the factors corresponding to the ASD DSM-IV classification (see supplementary material Table S4 for principle component analysis including the final selected items). Several items were removed because they loaded on multiple factors or did not load well on any of the factors (< 0.3). We checked the inter-correlation of the seven included autistic trait variables using Pearson correlation coefficients. Distribution of the social preference/skills and rigidity domain scores was also explored visually with the aid of a histogram. Lastly, we examined whether individuals with a suspected clinical ASD diagnosis (defined as DAWBA clinical ASD rating of > 0) had higher cumulative scores on the selected questions compared to those without. Individuals with a suspected ASD diagnosis were excluded from further analyses.
Association between autistic traits at age 14 and alcohol use in adolescents age 14–18
To explore the association between the autistic trait scores and alcohol use over time, we first looked at AUDIT-C scores at age 14, 16, and 18. Next, individual intercept and slope coefficients for the individual AUDIT-C scores over time were calculated for all subjects. The intercept refers to the AUDIT-C scores at age 14 and the slope shows the change of the AUDIT-C scores over time. An increase in AUDIT-C score, reflected by the slope coefficient, refers to an increase in alcohol use.
To test if drinking behaviors at baseline and their change over time were influenced by the cumulative score of the autistic trait domains, we used linear regression models including AUDIT-C intercept and slope coefficients as dependent variables and sum autistic trait score as independent variable, controlling for sex, site, presence of clinical DAWBA ratings of ADHD and IQ. We then examined the association between the social preference/skills and rigidity scores and amount of drinks per occasion in participants who indicated they were drinking at least once a month, using linear regression models. Lastly, we aimed to examine the differential influence of specific types of autistic traits on alcohol use by exploring the association between individual items and intercept and slope coefficients of the AUDIT-C scores.
All analyses were performed in Stata/MP 14.2 (StataCorp, College Station, TX) [41]. Statistical significance was determined as a p value < 0.006 (0.05/8) due to eight statistical tests done on the dependent variable.