The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.

Genetically informative research designs are becoming increasingly popular as a way to strengthen causal inference with their ability to control for genetic and shared environmental confounding. Co-twin control (CTC) models, a special case of these designs using twin samples, decompose the overall effect of exposure on outcome into a within- and between-twin-pair term. Ideally, the within-twin-pair term would serve as an estimate of the exposure effect controlling for genetic and shared environmental factors, but it is often confounded by factors not shared within a twin-pair. Previous simulation work has shown that if twins are less similar on an unmeasured confounder than they are on an exposure, the within-twin-pair estimate will be a biased estimate of the exposure effect, even more biased than the individual, unpaired estimate. The current study uses simulation and analytical derivations to show that while incorporating a covariate related to the nonshared confounder in CTC models always reduces bias in the within-pair estimate, it will be less biased than the individual estimate only in a narrow set of circumstances. The best case for bias reduction in the within-pair estimate occurs when the within-twin-pair correlation in exposure is less than the correlation in the confounder and the twin-pair correlation in the covariate is high. Additionally, the form of covariate inclusion is compared between adjustment for only one’s own covariate value and adjustment for the deviation of one’s own value from the covariate twin-pair mean. Results show that adjusting for the deviation from the twin-pair mean results in equal or reduced bias.

The Enrichment Study (ES) was designed to extend the Minnesota Twin Family Study (MTFS) by oversampling 11-year-old twins at especially high risk for substance use disorders by virtue of having a childhood disruptive disorder. The sample was ascertained from Minnesota birth records. To identify high-risk twins, we conducted telephone screening interviews for parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as well as indications of academic disengagement. Twins who exceeded a predetermined threshold were invited to participate. To facilitate comparison with the previously ascertained MTFS participants, a random sample of 11-year-old twins was also recruited. As part of the ES study, 499 twin pairs, and their parents, visited the University of Minnesota, where each participant completed a clinical interview, psychophysiological evaluation, and thorough assessment of environmental risk. We were highly successful in recruiting at-risk twins; 52% of the screened male twins and 41% of the screened females met criteria for a diagnosis of ADHD, CD, or oppositional defiant disorder (ODD). At the pair level, 63% of the screened pairs had at least one member with a childhood disruptive disorder. This article provides an overview of the study design and includes a review of recent findings using this sample of twins.

Research on communication between glia and neurons has increased in the past decade. The onset of neuropathic pain, a major clinical problem that is not resolved by available therapeutics, involves activation of spinal cord glia through the release of proinflammatory cytokines in acute animal models of neuropathic pain. Here, we demonstrate for the first time that the spinal action of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and spinal cord glial amplification of pain. Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose required limits its potential clinical utility. Here we show that intrathecal gene therapy for neuropathic pain is improved sufficiently using two, distinct synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic polymers used as i.t. gene-delivery systems are well-tolerated and improve the long-duration efficacy of pDNA-IL-10 gene therapy.

Genetic and environmental influences on symptoms of adult antisocial behavior (AAB) and alcohol dependence at ages 17, 20, and 24 were examined cross-sectionally and longitudinally in 188 monozygotic and 101 dizygotic male twin pairs. A moderate genetic influence on both AAB and alcohol dependence was found at each age, with a substantial proportion of this influence common to the two disorders, suggesting they share susceptibility genes. Biometrical models showed that continuity effects accounted for most of the stable variance in symptoms of both AAB and alcohol dependence, indicating that genetic and environmental effects associated with each of these disorders were similar at each age. Significant cross-lag effects (effects of alcohol dependence contributing to variance in AAB and vice versa) were observed at ages 20 and 24 for both disorders. The largest and theoretically most interesting of these effects indicated that one sixth of the genetic influence on AAB at age 20 was due to genetic effects associated with alcohol dependence at age 17. Thus, alcohol dependence symptoms at age 17 in particular had an effect on antisocial behavior symptoms at age 20, suggesting that alcohol involvement in adolescence may ensnare otherwise desisting youth in persistent antisocial behavior.The present study was supported in part by grants from the National Institute of Drug Abuse (DA 05147) and the National Institute on Alcohol Abuse and Alcoholism (AA09367). We are grateful to a number of individuals for their assistance in coding and entering data that were not previously available. Our special thanks are due to Irene Elkins, Linda Springer, Kari Melchert, and Kristen Abernethy for their gracious and timely help.

We examined heritability of error rate on the antisaccade task among female twin youths. This task appears to be sensitive to prefrontal functioning, providing a measure of individual differences in inhibitory control associated with genetic risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year-olds, comprising the two cohorts of female twins from the Minnesota Twin Family Study, a population-based investigation of substance abuse and related psychopathology. We used biometric model-fitting methods to determine the relative magnitude of genetic and environmental influences on performance. In both age cohorts, the best fitting model contained additive genes and nonshared environment. Despite substantial age-related differences in mean performance levels (effect size = .81), additive genes accounted for greater than half the variance in performance in both age cohorts. These results are consistent with the hypothesis that antisaccade error rate might serve as an endophenotype for behavior disorders reflecting frontal lobe dysfunction or problems with inhibitory control.

The present study examined event-related potentials (ERPs) elicited by a visual discrimination task in a community sample of adult males with a lifetime diagnosis of alcohol dependence. Study participants were subtyped by the presence of additional comorbid disorders (antisocial personality, depression, and drug abuse or dependence). In all groups of alcohol-dependent subjects, even those without any additional comorbid disorders, P3 amplitude differed from that of a comparison group. Alcohol-dependent subjects with a diagnosis of illicit drug abuse or dependence, especially if they had antisocial personality as well, had the smallest amplitude responses. The amplitude profile of the P3 across the parietal electrodes used as active sites was flattened among alcoholic subjects, with P3 amplitude disproportionately reduced at the midline. Among alcoholic subjects with a lifetime diagnosis of depression, the flattened amplitude profile was due to elevated mean amplitude of the P3 at lateral leads, especially P4, relative to the comparison group. Alterations in ERP responses appear to be a general characteristic of alcoholism in men, although the presence of other comorbid disorders, particularly drug abuse or dependence together with antisocial personality, results in the greatest reductions in P3 amplitude.