Harmonized Phenotypes for Anxiety, Depression, and Attention-Deficit Hyperactivity Disorder (ADHD)

Abstract

In multi-cohort consortia, the problem often arises that a phenotype is measured using different questionnaires. This study aimed to harmonize scores based on the Child Behaviour Check List (CBCL) and the Strength and Difficulties Questionnaire (SDQ) for anxiety/depression and ADHD. To link the scales, we used parent reports on 1330 children aged 10–11.5 years from the Raine study on both SDQ and CBCL. Harmonization was done based on Item Response Theory. We started from existing CBCL and SDQ scales related to anxiety/depression and ADHD (theoretical approach). Next, we conducted a data-driven approach using factor analysis to validate the theoretical approach. Both approaches yielded similar scales, validating the combination of existing scales. In addition, we studied the impact of harmonized (IRT-based) scores on the statistical power of the results in meta-analytic gene-finding studies. The results showed that the IRT-based harmonized scores increased the statistical power of the results compared to sum scores, even with an equal sample size. These findings can help future researchers to harmonize data from different samples and/or different questionnaires that measure anxiety, depression, and ADHD, in order to obtain the larger sample sizes, to compare research results across subpopulations or to increase generalizability, the validity or statistical power of research results. We recommend using our item parameters to estimate harmonized scores that represent commensurate phenotypes across cohorts, and we explained in detail how other researchers can use our results to harmonize data in their studies.

Harmonizing the CBCL and SDQ ADHD scores by using linear equating, kernel equating, item response theory and machine learning methods

“…This type of information (raw data at the item level), when it is available, could be used in a powerful way by implementing Item Response Theory (IRT) models. These models take into account not only differences between test takers, but also between the items, for instance their relative difficulty ( van den Berg et al, 2014 ; Jabrayilov et al, 2016 ; Sansivieri et al, 2017 ; Jović et al, 2022 ; Mansolf et al, 2022 ).…”

“…In more complex IRT models (e.g., Generalized Partial Credit Model), participants` responses are determined not only by their latent trait value and difficulty of the item, but also by discrimination parameter of the item (refers to the strength of the relationship between trait level and participants` responses on the item; see Embretson and Reise (2000) for more details). For example, van den Berg et al (2014) used Generalized Partial Credit Model to harmonize neuroticism and extraversion scores, while Jović et al (2022) used it to harmonize anxiety/depression and ADHD scores of CBCL and SDQ scales. Mansolf et al (2022) used IRT to harmonize Internalizing, Externalizing, and Total Problems domains from CBCL and SDQ.…”

“… Jović et al (2022) focused on harmonizing ADHD and anxiety/depression scores obtained by using CBCL and SDQ on a sample of 1,330 participants between 10 and 11.5 years old from Australia. Authors used IRT to harmonize CBCL and SDQ.…”

“… Stevens et al (2021) used a high-risk population, while Mansolf et al (2022) and Jović et al (2022) harmonized data on a general population. They used different harmonization methods, equipercentile equating ( Stevens et al, 2021 ) and IRT ( Jović et al, 2022 ), while Mansolf et al (2022) compared the results of both of those approaches. Also, they all harmonized CBCL and SDQ on a different level of granularity.…”

“…Also, they all harmonized CBCL and SDQ on a different level of granularity. Stevens et al (2021) and Mansolf et al (2022) harmonized externalising, internaling and total scores, while Jović et al (2022) focused on more specific subscales (Anxiety/Depression and Hyperactivity/attention problems). In sum, it is unknown which harmonization method works the best in the case of CBCL and SDQ while harmonizing hyperactivity/attention problems.…”