Danielle M Dick

Virginia Commonwealth University, Ричмонд, Virginia, United States

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Publications (244)973 Total impact

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    ABSTRACT: Background: Genetic and environmental factors influence substance use behaviors in youth. One of the known environmental risk factors is exposure to life stressors. The aim of this project is to study the interaction between NR3C1 and CRHBP, genes thought to be involved in stress pathways, exposure to stressful life events, and adolescent alcohol use/misuse. Methods: The sample included 541 African American individuals (ages 13-18) from the Genes, Environment, and Neighborhood Initiative, a subset of the Mobile Youth Survey sample from whom DNA and more extensive phenotypic data were collected. Participants were selected from high poverty neighborhoods in Mobile, Alabama with potential exposure to a variety of extreme life stressors. Results: A measure of stressful life events was significantly predictive of alcohol use/misuse. In addition, this association was significantly dependent upon the number of putative risk variants at rs1715749, a SNP in CRHBP (p≤0.006). There was no significant interaction between NR3C1 and stressful life events with respect to alcohol use/misuse, after taking into account multiple testing. Conclusions: These findings suggest that CRHBP variants are potentially relevant for adolescent alcohol use/misuse among African American youth populations being reared within the context of stressful life events, and warrants replication.
    No preview · Article · Jan 2016 · Substance Abuse
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    ABSTRACT: Aims: To determine 1) the prospective associations of conduct problems during early adolescence with tobacco, alcohol and cannabis use in young adulthood and 2) to what extent these associations are due to overlapping genetic versus environmental influences. Design: A prospective twin study using biometric twin modelling. Setting: Finland. Participants: 1847 Finnish twins (943 males and 904 females) were interviewed in early adolescence, of which 73% (N=1353, 640 males and 713 females) were retained in young adulthood. Measurements: Symptom counts of conduct disorder (CD) criteria were obtained from a semi-structured clinical interview in early adolescence (age 14-15 years, M=14.2, SD=0.15). Frequency of alcohol, tobacco, and cannabis use was obtained from a semi-structured clinical interview in young adulthood (age 19.9-26.6 years, M=22.4, SD=0.7). Findings: We found modest to moderate phenotypic correlations (r=0.16 to 0.35) between early adolescent CD symptoms and substance use in young adulthood. In males, the phenotypic correlations of CD symptoms with all three substance use variables are largely explained by overlapping genetic influences. In females, overlapping shared environmental influences predominantly explain the phenotypic correlation between CD symptoms and tobacco and cannabis use. Conclusions: Conduct disorder symptoms in early adolescence appear to moderately predict substance use in early adulthood. In males, genetic influences seem to be most important in explaining the relationship between conduct disorder symptoms and substance use whereas in females, shared environmental influences seem to be most important. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Addiction

  • No preview · Article · Nov 2015
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    ABSTRACT: Researchers have long observed that problem behaviors tend to cluster together, particularly among adolescents. Epidemiological studies have suggested that this covariation is due, in part, to common genetic influences, and a number of plausible candidates have emerged as targets for investigation. To date, however, genetic association studies of these behaviors have focused mostly on unidimensional models of individual phenotypes within European American samples. Herein, we compared a series of confirmatory factor models to best characterize the structure of problem behavior (alcohol and marijuana use, sexual behavior, and disruptive behavior) within a representative community-based sample of 592 low-income African American adolescents (50.3% female), ages 13 to 18. We further explored the extent to which 3 genes previously implicated for their role in similar behavioral dimensions (CHRM2, GABRA2, and OPRM1) independently accounted for variance within factors specified in the best-fitting model. Supplementary analyses were conducted to derive comparative estimates for the predictive utility of these genes in more traditional unidimensional models. Findings provide initial evidence for a bifactor structure of problem behavior among African American adolescents and highlight novel genetic correlates of specific behavioral dimensions otherwise undetected in an orthogonal syndromal factor. Implications of this approach include increased precision in the assessment of problem behavior, with corresponding increases in the reliability and validity of identified genetic associations. As a corollary, the comparison of primary and supplementary association analyses illustrates the potential for overlooking and/or overinterpreting meaningful genetic effects when failing to adequately account for phenotypic complexity.
    No preview · Article · Oct 2015 · Journal of Clinical Child & Adolescent Psychology
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    ABSTRACT: Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N=2056, 1240 females) of the "Spit for Science" sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains - including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety - were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: 1) use of all four substances; 2) alcohol, tobacco, and cannabis use; and 3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use.
    Full-text · Article · Oct 2015 · Frontiers in Psychiatry

  • No preview · Article · Oct 2015 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-typespecific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
    Full-text · Article · Sep 2015
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    ABSTRACT: Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
    Full-text · Article · Sep 2015 · PLoS ONE
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    ABSTRACT: Background: The current longitudinal study examined associations between interpersonal potentially traumatic events (PTEs; i.e., sexual or physical assault) and changes in alcohol consumption among incoming college students. Methods: 1197 students (68% female) participating in a university-wide research study were included in analyses. Assessments were administered at three time-points and included measures of alcohol use, PTEs (Life Events Checklist), and a screener for possible PTSD symptoms (abbreviated Primary Care PTSD Screen). Linear growth curve models were fit to the three repeated measures of alcohol quantity and frequency to determine the role of pre-college and college-onset interpersonal PTEs and possible PTSD symptoms on patterns of alcohol use. Results: Pre-college interpersonal PTE was associated with greater baseline alcohol use for female but not male students. College-onset interpersonal PTE predicted greater alcohol use at concurrent and future assessments for women but not men, beyond the effects of pre-college PTE. Pre-college possible PTSD symptoms did not predict baseline or change in alcohol use. Conclusions: There may be a stronger and longer-lasting impact of interpersonal PTE for college women compared to men on alcohol phenotypes, although replication in studies oversampling men endorsing interpersonal PTE is needed.
    No preview · Article · Sep 2015 · Addictive Behaviors
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    ABSTRACT: The purpose of this study was to address two methodological issues that have called into question whether previously reported gene-environment interaction (GxE) effects for adolescent alcohol use are 'real'. These issues are (1) the potential correlation between the environmental moderator and the outcome across twins and (2) non-linear transformations of the behavioral outcome. Three environments that have been previously studied (peer deviance, parental knowledge, and potentially stressful life events) were examined here. For each moderator (peer deviance, parental knowledge, and potentially stressful life events), a series of models was fit to both a raw and transformed measure of monthly adolescent alcohol use in a sample that included 825 dizygotic (DZ) and 803 monozygotic (MZ) twin pairs. The results showed that the moderating effect of peer deviance was robust to transformation, and that although the significance of moderating effects of parental knowledge and potentially stressful life events were dependent on the scale of the adolescent alcohol use outcome, the overall results were consistent across transformation. In addition, the findings did not vary across statistical models. The consistency of the peer deviance results and the shift of the parental knowledge and potentially stressful life events results between trending and significant, shed some light on why previous findings for certain moderators have been inconsistent and emphasize the importance of considering both methodological issues and previous findings when conducting and interpreting GxE analyses.
    No preview · Article · Aug 2015 · Twin Research and Human Genetics
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    ABSTRACT: This study examined the effects of racial discrimination, community violence, and stressful life events on internalizing problems among African American youth from high-poverty neighborhoods (N = 607; 293 boys; Mage = 16.0 years, SD = 1.44 years). Mediated effects via externalizing problems on these relations were also examined, given the high comorbidity rate between internalizing and externalizing problems. Externalizing problems partially mediated the effect of stressful life events on internalizing problems and fully mediated the effect of racial discrimination for boys but not for girls. Exposure to violence had a significant indirect effect on internalizing problems via externalizing problems. The findings call for greater attention to internalizing problems among African American youth and pathways to internalizing problems via externalizing problems.
    No preview · Article · Jul 2015 · Journal of Research on Adolescence
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    ABSTRACT: Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analysis (WGCNA) of genome-wide mRNA and microRNA (miRNA) expression in the Nucleus Accumbens (NAc) of 18 subjects with alcohol dependence (AD) and 18 matched controls (from the Australian Brain Donor Programs Resource Centre), six mRNA and three miRNA modules were significantly correlated with AD (Bonferroni-adj. p≤ 0.05). Two mRNA modules were associated with neuronal specific marker genes and four were associated with glial cell specific marker genes (adj. p<0.05). Using gene set enrichment analysis, the neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling, while the glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling in immune system (all adj. p≤ 0.05). In the significant mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. Follow up integration of the mRNA and miRNA hub genes' expression with genome-wide genotypic data identified 591 cis-eQTLs and 62 cis-eQTLs, respectively. After adjusting for the number of tests, the mRNA cis-eQTLs were significantly enriched for AD GWAS signals in an independent sample from the Collaborative Study on Genetics of Alcohol (COGA) (adj. p=0.024), providing a novel biological role for these association signals. In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
    No preview · Conference Paper · Jun 2015
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    ABSTRACT: We examine whether parental externalizing behavior has an indirect effect on adolescent externalizing behavior via elevations in life events, and whether this indirect effect is further qualified by an interaction between life events and adolescents' GABRA2 genotype (rs279871). We use data from 2 samples: the Child Development Project (CDP; n = 324) and FinnTwin12 (n = 802). In CDP, repeated measures of life events, mother-reported adolescent externalizing, and teacher-reported adolescent externalizing were used. In FinnTwin12, life events and externalizing were assessed at age 14. Parental externalizing was indexed by measures of antisocial behavior and alcohol problems or alcohol dependence symptoms in both samples. In CDP, parental externalizing was associated with more life events, and the association between life events and subsequent adolescent externalizing varied as a function of GABRA2 genotype (p ≤ .05). The association between life events and subsequent adolescent externalizing was stronger for adolescents with 0 copies of the G minor allele compared to those with 1 or 2 copies of the minor allele. Parallel moderation trends were observed in FinnTwin12 (p ≤ .11). The discussion focuses on how the strength of intergenerational pathways for externalizing psychopathology may differ as a function of adolescent-level individual differences. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    No preview · Article · Jun 2015 · Journal of Abnormal Psychology
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    ABSTRACT: Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.
    Full-text · Article · Jun 2015 · Journal of Policy Analysis and Management
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    ABSTRACT: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior. The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents. Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task. Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.
    No preview · Article · May 2015 · American Journal of Psychiatry
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    Danielle M. Dick · Linda C. Hancock
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    ABSTRACT: Too often basic research on etiological processes that contribute to substance use outcomes is disconnected from efforts to develop prevention and intervention programming. Substance use on college campuses is an area of concern where translational efforts that bring together basic scientists and prevention/intervention practitioners have potential for high impact. We describe an effort at a large, public, urban university in the United States to bring together researchers across the campus with expertise in college behavioral health with university administration and health/wellness practitioners to address college student substance use and mental health. The project "Spit for Science" examines how genetic and environmental influences contribute to behavioral health outcomes across the college years. We argue that findings coming out of basic research can be used to develop more tailored prevention and intervention programming that incorporates both biologically and psychosocially influenced risk factors. Examples of personalized programming suggest this may be a fruitful way to advance the field and reduce risky substance use.
    Full-text · Article · May 2015 · Frontiers in Psychology
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    ABSTRACT: A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web-based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression-anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression-anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression-anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    No preview · Article · May 2015 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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    ABSTRACT: The gene GRM8, a metabotropic glutamate receptor, has emerged as a gene of interest for its possible role in the development of alcohol dependence, with evidence of association with an electrophysiological endophenotype and level of response to alcohol as well as suggestive evidence of association with alcohol dependence. The present study further investigated the association between GRM8 and alcohol dependence symptom counts among young adults using a new sample of individuals collected as part of the prospective sample (ages 18-26 years; N = 842) from the Collaborative Study on the Genetics of Alcoholism (COGA). Two single-nucleotide polymorphisms were significantly associated with alcohol dependence in European Americans using the Nyholt corrected p value of .007: rs886003 (β = -.212, p = .0002) and rs17862325 (β = -.234, p < .0001), but not in African Americans, likely because of the lower power to detect association in this group. These results further implicate the role of glutamate receptor genes such as GRM8 in the development of alcohol dependence.
    No preview · Article · May 2015 · Journal of studies on alcohol and drugs
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    ABSTRACT: Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case-control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10−7) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.
    Full-text · Article · Apr 2015 · Translational Psychiatry
  • Jessica E. Salvatore · Danielle M. Dick
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    ABSTRACT: The idea that both genetic and environmental influences contribute to behavioral outcomes is widely accepted. However, the practice of examining candidate Gene × Environment interaction (cGxE) is controversial. In this article, we summarize some of the key issues involved in cGxE research and provide recommendations for work in this area. Highlighted challenges include the selection of the gene, the development of the cGxE hypothesis, and the coding of the genotype. To address these challenges and gain confidence in cGxE findings, we recommend using empirical data to select and code genes/variants, using theory to develop cGxE hypotheses and a rigorous and transparent approach to hypothesis testing. Family researchers have much to offer to the study of Gene × Environment research in view of their process-oriented theories that are grounded in decades of nuanced measurement of the environment; implementing these best practices will help deliver on that promise.
    No preview · Article · Apr 2015 · Journal of Marriage and Family

Publication Stats

8k Citations
973.00 Total Impact Points

Institutions

  • 2007-2015
    • Virginia Commonwealth University
      • • Department of Psychiatry
      • • Virginia Institute for Psychiatric and Behavioral Genetics
      Ричмонд, Virginia, United States
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, California, United States
  • 2010
    • University of Amsterdam
      • Department of Education
      Amsterdamo, North Holland, Netherlands
  • 2008
    • University of Jyväskylä
      • Department of Psychology
      Jyväskylä, Central Finland, Finland
    • Washington School of Psychiatry
      Washington, Washington, D.C., United States
  • 2004-2008
    • Washington University in St. Louis
      • • Department of Psychiatry
      • • Department of Psychology
      San Luis, Missouri, United States
  • 2002-2008
    • Indiana University-Purdue University Indianapolis
      • • Department of Medical and Molecular Genetics
      • • Department of Psychiatry
      Indianapolis, Indiana, United States
    • University of Iowa
      • Department of Psychiatry
      Iowa City, Iowa, United States
  • 2003-2005
    • Indiana University-Purdue University School of Medicine
      • Institute of Psychiatric Research
      Indianapolis, Indiana, United States
  • 2000-2004
    • Indiana University Bloomington
      • Department of Psychological and Brain Sciences
      Bloomington, Indiana, United States
  • 2001
    • Indiana University Health
      Bloomington, Indiana, United States
  • 2000-2001
    • University of Helsinki
      • Department of Dental Public Health
      Helsinki, Uusimaa, Finland