Abstract
The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989–2004. We summarize early recruitment, assessment, retention, and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and non-twin siblings. Our adolescent and young adult neuroimaging sample (n=600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.
Keywords: twins, longitudinal, temperament, developmental psychopathology, neuroimaging, behavior genetics
The Wisconsin Twin Project began in the early 1990s in the state of Wisconsin, which is north centrally located in the United States. The design of the Wisconsin Twin Project accommodates a range of research on emotional and cognitive development, with a strong emphasis on clinical outcomes. Assessments for some participants began in the prenatal period, and the oldest age of follow-up was at approximately 24 years of age.
The broad themes of our results span psychophysiology, temperament development, gene-environment interplay, and other aspects of mental and physical health. Many studies incorporate observational behavior and laboratory temperament assessments that were partially developed in our lab (Buss & Goldsmith, 2000; Gagne, Van Hulle, Aksan, Essex, & Goldsmith, 2011; Goldsmith et al., 2010; Planalp, Van Hulle, Gagne, & Goldsmith, 2017). Several of our neuroimaging studies incorporate the MZ difference design (Adluru et al., 2017; Alisch et al., 2017; Cambridge et al., 2016; Carroll, Planalp, Van Hulle, & Goldsmith, 2019). Recent empirical results from more than 30 papers are summarized in Schmidt et al. (2019).
Sample, recruitment, and retention
The Wisconsin Twin Project sample is based on birth-record-based cohorts of twins born in the state of Wisconsin during years 1989–2004 (Goldsmith, Lemery-Chalfant, Schmidt, Arneson, & Schmidt, 2007; Lemery-Chalfant, Goldsmith, Schmidt, Arneson, & Van Hulle, 2006; Schmidt et al., 2013; Van Hulle, Lemery-Chalfant, & Goldsmith, 2002). According to the U.S. Census Bureau and other data, of 50 states, Wisconsin ranks 20th in total population, 25th in physical size, 23rd in median household income, 20th in gross domestic product, 11th in percentage who are high school graduates, 26th in percentage of college graduates, and 37th in percentage of persons who identity as racial or ethnic minorities. Although differences in state ranks in these categories often reflect small differences, Wisconsin is clearly about average in many characteristics among U.S. states. As a result, data from Wisconsin are likely to represent the U.S. population reasonably well.
After nearly 30 years, the research program encompasses a series of longitudinal studies that span infancy to early adulthood (see Figure 1), with another currently planned longitudinal follow-up in early adulthood. Families entered the Wisconsin Twin Project through two primary mechanisms: (1) Multimethod recruiting (e.g., advertising, recruiting from twin groups); and (2) State birth records, both depicted at the top of Figure 1. No new recruiting occurred after the infant-toddler years except for subsets of participants for Studies 3 and 5. The arrows in Figure 1 depict sequences of subsequent testing occasions across development. The boxes in Figure 1 represent studies, which each comprise one or more testing occasions. A given study typically yields several published papers, some of which span studies. Each study includes a target age (e.g., birth, age 12–18 years). The arrows also depict what earlier and later data exist. For instance, the sample in Study 2c were tested previously in either Study 1 or Study 2a. A portion of the Study 2c sample was also tested in Study 4. Study 2c encapsulated three separate testing occasions at ages 7, 12, and 15 years. Detailed descriptions of early assessment were reported in Schmidt et al. (2013).
Figure 1.
Wisconsin Twin Research Project Overview
Note. Parent and sibling data were also collected in studies 1–4, 6, and 7.
As an illustration, consider a twin pair recruited from state birth records (top center of Figure 1). Generally, the twins would have still been infants when we accessed the birth records. The parents were sent an invitation letter and subsequently agreed to be contacted for future research participation. The first parent interview and survey about toddler temperament, parenting, and challenging behaviors occurred in Study 2a, when the twins were approximately 24 months old. After the toddler screen, they were assessed again via parental report at age 7 years in Study 2b. If either twin’s scores met selection criteria in Study 2b (e.g., mild enrichment for psychopathology), they were tested up to three times in Study 2c at ages 7, 12 and 15 years, and a final time around age 17 years in Study 6 with neuroimaging and behavioral assessment. The arrows show other pathways to Study 6.
As another example, consider a different twin pair located under the multimethod recruitment (e.g., local advertisement) shortly after birth, at an age before state birth records were available. This twin pair was first tested in Study 1 and tested with lab-based observational assessment on multiple occasions between birth and age 3 years. This twin pair was tested again in Study 5 with laboratory measurement of psychophysiology and then a final time in Study 6, the same final study as the twin pair described in previous paragraph.
Twin family recruitment and early results were covered in prior overviews of the project (Goldsmith et al., 2007; Schmidt et al., 2013). Briefly, initial contact was attempted with a mailed letter and contact form. Contact was maintained with multiple phone numbers, email addresses, a toll-free phone number, and secondary contact information from a family friend or relative. Sample retention efforts included newsletters and a website devoted to participant communication. We attempted to recapture twin families at later testing occasions, where possible. We used web-based tracing methods (e.g., public court records) to locate families whom we lost contact with. The University of Wisconsin Survey Center also provided tracing services. All of these procedures helped maintain the research sample longitudinally.
The research is conducted at the University of Wisconsin–Madison’s Waisman Center and the Department of Psychology (https://goldsmithtwins.waisman.wisc.edu/). Procedures in studies under the Wisconsin Twin Project were approved by University of Wisconsin–Madison Internal Review Boards and comply with the Helsinki Accords of 1975, as revised in 2008.
The Wisconsin Twin Project’s signature approach is its depth and breadth of phenotyping (see Table 1). Sample sizes shown in Table 1 depict longitudinal data collection. For instance, 100% of the sample of 311 twin pairs with neuroimaging were tested at the earlier waves of data collection.
Table 1.
Research Modality and Sample Sizes by Study
| Study | Approx. N twin pairs | Research modality |
||||
|---|---|---|---|---|---|---|
| Interview | Survey | Behavior Assessment | Cortisol | Multimodal Brain Scan | ||
| Birth – 3 years | 784 | ✓ | ✓ | ✓ | ✓ | |
| Toddler screen | 3261 | ✓ | ✓ | |||
| Age 7 screen | 2004 | ✓ | ||||
| Age 7–15 longitudinal psychopathology1 | 990 | ✓ | ✓ | ✓ | ✓ | |
| Adolescent and young adult brain & behavior2 | 300 | ✓ | ✓ | ✓ | ✓ | |
| Autism spectrum | 191 | ✓ | ✓ | ✓ | ||
Note. Interview and written survey measures of sensory over-responsivity were included in all studies. Medical record data from the twin pregnancy and birth exist for most twins.
Genotyping was done with the longitudinal psychopathology study.
Neuroimaging studies comprise a pair of studies, Studies 6 & 7 from Figure 1. The vast majority (85%) of twins were participants of the Research Domain Criteria (RDoC) neuroimaging study.
Twin zygosity was classified with multiple methods across testing occasions. Initially, zygosity was classified with the Zygosity Questionnaire for Young Children (Goldsmith, 1991). Observational ratings of zygosity were collected during in-person assessments. Ambiguous zygosity was resolved by genotyping.
Twin Neuroimaging Studies
Twin neuroimaging was a focus of the project during the past decade. The neuroimaging studies assessed brain structure and function with multimodal MRI. Although MRI methods have varied with improvements in technology, we use T1- and T2-weighted structural scans, diffusion weighted imaging, arterial spin labeling, resting state fMRI, and task-related fMRI. The combined neuroimaging sample comprises 600 twins (300 pairs), all of whom have been studied previously, some on seven prior testing occasions. We over-sampled MZ twins (66%). Some of our early neuroimaging and epigenetic studies use the MZ difference design (Adluru et al., 2017; Alisch et al., 2017; Burghy et al., 2016). The twin neuroimaging data were also used to illustrate novel computational MRI methods (Chung, Luo, Adluru et al., 2018; Chung, Luo, Leow et al., 2018; Huang, Chung, Carroll, & Goldsmith, 2019).
A majority of our neuroimaging work has incorporated Research Domain Criteria (RDoC) as a framework for the behavioral assessments. Specifically, the RDoC twin study used longitudinal and quantitative genetic approaches to establish developmental antecedents and neural substrates for the RDoC positive valence systems (e.g., anticipatory positive affect and contentment) and negative valence systems (e.g., acute fear, potential threat/anxiety, frustrative non-reward, and loss) (Cuthbert, 2014). The RDoC twin study aimed to (a) establish distinctiveness, stability, and external validity of each RDoC construct during childhood and adolescence; (b) investigate the relationship between brain structure and function (via MRI) and concurrent and longitudinal RDoC measures; and (c) utilize the MZ difference design to highlight early environmental contributions to later brain structure and function. In the MRI analyses, we focused more on white matter microstructure and on resting state and task-related functional measures (that is, circuitry and networks) than on grey matter structure.
The RDoC twin study enrolled 518 monozygotic (56%) and dizygotic twin individuals (mean age = 17.4 years, SD = 2.2 years). Approximately 70% were under age 18 years at the time of assessment. Parents (88% mothers) of adolescents completed surveys. Data collection concluded in early 2019. Tables 2 and 3 list the principal twin individual-level instruments and family-level instruments collected concurrently with neuroimaging data for the RDoC sample.
Table 2.
Principal Individual-Level Instruments for the Adolescent and Young Adult RDoC Brain and Behavior Study
| Adolescent instruments | Longitudinal data available |
|---|---|
| Temperament | |
| Affective forecasting questions | |
| Early Adolescent Temperament Questionnaire-Revised (EATQ-R; Ellis & Rothbart, 2001)b | ✓ |
| Positive Affect Negative Affect Scales (PANAS; Watson et al., 1988) | ✓ |
| Psychopathology symptoms | |
| Adult Sensory Profile (Brown & Dunn, 2002) | ✓ |
| Anticipatory and Consummatory Interpersonal Pleasure Scale-Adolescent (ACIPS-A; Gooding et al., 2015) | |
| Antisocial Process Screening Device (APSD; Frick & Hare, 2001)a,b | ✓ |
| Behavioral Inhibition & Activation Scales (BIS/BAS; Carver & White, 1994) | |
| Children’s Depression Inventory (CDI; Kovacs, 2003), Beck Depression Inventory (BDI; Beck et al., 1996)b | ✓ |
| Penn State Worry Questionnaire (Meyer et al., 1990) | |
| Psychological Well-Being Scale (Ryff & Keyes, 1995) | |
| Sensory Over-responsivity Checklist (Schoen et al., 2008) | ✓ |
| Substance use questions | |
| State Trait Anxiety Inventory (STAI; Spielberger et al., 1983) | |
| Attributional style | |
| Children’s Attributional Style Questionnaire-Revised (CASQ-R; Thompson et al., 1998) | ✓ |
| Children’s Rejection Sensitivity Questionnaire (CRSQ; Downey et al., 1998), Adult Rejection Sensitivity Questionnaire (ARSQ; Berenson et al., 2009)b | ✓ |
| Response Styles Questionnaire (RSQ; Kasch et al., 2001)b | ✓ |
| Delay Discounting Questionnaire (da Matta et al., 2012) | |
| Computer-based behavior battery | |
| Modified Iowa Gambling Task (Hungry Donkey; Crone & van der Molen, 2004) | |
| Affective Go No-Go (Cambridge Cognition, 2019; Robbins et al., 1994) | |
| Point Subtraction Aggression Paradigm (Cambridge Cognition, 2019) | |
| Experiences: Parenting, peer, relationships, and stress | |
| Adolescent Perceived Event Scale (APES; Compas et al., 1987)b | ✓ |
| Demographics /social and economic status questions | ✓ |
| Intolerance of Uncertainty Scale-Short Form (Freeston et al., 1994) | |
| Reactive-Proactive Aggression Questionnaire (Raine et al., 2006)b | |
| Sensitivity to Punishment and Reward Questionnaire (Torrubia et al., 2001) | |
| Twin Inventory of Relationships and Experiences (TIRE; Carbonneau et al., 2001)b | ✓ |
| Young Adult Social Behavior Scale-Relational Aggression Scale (Crothers et al., 2009) | |
| Puberty | |
| Morris & Udry assessment of pubertal development (Morris & Udry, 1980) | ✓ |
| Peterson Pubertal Development Scale (Petersen et al., 1988) | ✓ |
Notes. N=518 MZ and DZ twins (68% were adolescents; 56% MZ).
Co-twin ratings also collected.
Adult twin ratings collected
Table 3.
Principal Family-Level Instruments for the Adolescent and Young Adult Brain and Behavior Study
| Parent Instruments | Longitudinal data available |
|---|---|
| Temperament of offspring | |
| Early Adolescent Temperament Questionnaire-Parent Report (EATQ-R Parent Report; Ellis & Rothbart, 2001)a | ✓ |
| Psychopathology symptoms of self | |
| Beck Depression Inventory (BDI; Beck et al., 1996) | ✓ |
| Experiences: Parenting, peer, relationships, and stress | |
| Barnett Role Overload (Baruch & Barnett, 1986) | ✓ |
| Discipline Measure (Patterson & Stouthamer-Loeber, 1984)a | ✓ |
| Family Expressiveness Questionnaire (Halberstadt, 1986) | ✓ |
| Financial Stress (Pearlin et al., 1981) | ✓ |
| Parental Monitoring (Small & Kerns, 1993)a | ✓ |
| Parenting Stress Index (PSI; Abidin, 1995) | ✓ |
| Student success questionsa | ✓ |
| Twin Inventory of Relationships and Experiences (TIRE; Carbonneau et al., 2001)a | ✓ |
| Puberty Status of Offspring | |
| Peterson Pubertal Development Scales (Petersen et al., 1988)a | ✓ |
Note: We collected parent ratings for twins under age 18 years at the time of MRI testing.
Completed separately for each twin.
Future Directions
Although the panel is no longer being expanded, we maintain contact with the full panel of twin families through biannual newsletters and a website. These data could support diverse empirical investigations. The sample sizes afford the possibility to examine selected subsamples (e.g., clinical cases, the MZ twin difference sample). Planned research includes new assessments with early adulthood outcomes, deeper assessment of experiential differences using ecological momentary assessment, and a greater focus on general health outcomes. We welcome interest in collaboration. A portion of our data, including the neuroimaging, resides in the National Data Archive (all data related to the study named Validating RDoC for Children and Adolescents: A Twin Study with Neuroimaging, collection #2105). https://ndar.nih.gov/edit_collection.html?id=2105&source=RDoCdb&funding=NIH+-+Extramural
Acknowledgements
This work was supported by the National Institute of Mental Health (R01-MH101504, R01-MH059785, R01-MH069793, R37-MH050560), the Wisconsin Center for Affective Science (P50-MH069315), two Conte Neuroscience Centers (P50-MH084051, P50-MH100031), the Wallace Research Foundation, and the National Alliance for Autism Research. Infrastructure support was provided by the Waisman Center via core support from the National Institute of Child Health and Human Development (P30-HD003352, U54-HD090256). The authors owe special gratitude to Wisconsin twins and their families for their generous time for research participation. We also thank a large team of scientific collaborators, graduate students, postdoctoral trainees, research staff, and undergraduate student research assistants.
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