Danielle M Dick

Virginia Commonwealth University, Ричмонд, Virginia, United States

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Publications (231)947.15 Total impact

  • [Show abstract] [Hide abstract]
    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.
    PLoS ONE 09/2015; 10(9). DOI:10.1371/journal.pone.0137671. · 3.23 Impact Factor
  • Addictive Behaviors 09/2015; DOI:10.1016/j.addbeh.2015.09.014 · 2.76 Impact Factor
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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.
    Twin Research and Human Genetics 08/2015; DOI:10.1017/thg.2015.56 · 2.30 Impact Factor
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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.
    Journal of Research on Adolescence 07/2015; DOI:10.1111/jora.12213 · 1.99 Impact Factor
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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.
    Research Society on Alcoholism, San Antonion; 06/2015
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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).
    Journal of Abnormal Psychology 06/2015; DOI:10.1037/abn0000066 · 4.86 Impact Factor
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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.
    Journal of Policy Analysis and Management 06/2015; 34(3). DOI:10.1002/pam.21811 · 0.93 Impact Factor
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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.
    American Journal of Psychiatry 05/2015; 172(6):appiajp201414030382. DOI:10.1176/appi.ajp.2014.14030382 · 12.30 Impact Factor
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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.
    Frontiers in Psychology 05/2015; 6. DOI:10.3389/fpsyg.2015.00544 · 2.80 Impact Factor
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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.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 05/2015; 168(5). DOI:10.1002/ajmg.b.32320 · 3.42 Impact Factor
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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.
    Journal of studies on alcohol and drugs 05/2015; 76(3):414-418. DOI:10.15288/jsad.2015.76.414 · 2.76 Impact Factor
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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.
    Translational Psychiatry 04/2015; 5(4):e558. DOI:10.1038/tp.2015.36 · 5.62 Impact Factor
  • 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.
    Journal of Marriage and Family 04/2015; 77(2). DOI:10.1111/jomf.12164 · 3.01 Impact Factor
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    Jessica E. Salvatore · Irving I. Gottesman · Danielle M. Dick
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    ABSTRACT: The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically influenced pathways toward AUD.
    03/2015; 2(1):76-90. DOI:10.1007/s40429-015-0046-y
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    ABSTRACT: In this project, we aimed to bring large-scale gene identification findings into a developmental psychopathology framework. Using a family-based sample, we tested whether polygenic scores for externalizing disorders-based on single nucleotide polymorphism weights derived from genome-wide association study results in adults (n = 1,249)-predicted externalizing disorders, subclinical externalizing behavior, and impulsivity-related traits adolescents (n = 248) and young adults (n = 207), and whether parenting and peer factors in adolescence moderated polygenic risk to predict externalizing disorders. Polygenic scores predicted externalizing disorders in adolescents and young adults, even after controlling for parental externalizing disorder history. Polygenic scores also predicted subclinical externalizing behavior and impulsivity traits in the adolescents and young adults. Adolescent parental monitoring and peer substance use moderated polygenic scores to predict externalizing disorders. This illustrates how state of the science genetics can be integrated with psychological science to identify how genetic risk contributes to the development of psychopathology.
    03/2015; 3(2):189-201. DOI:10.1177/2167702614534211
  • Kenneth S Kendler · John Myers · Danielle Dick
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    ABSTRACT: Peer group deviance (PGD) is strongly associated with current and future externalizing behaviors. Debate remains about the degree to which this association arises from social selection. The first year of university constitutes a social experiment in which most individuals leave their home environment and recreate for themselves a new peer group. PGD was measured in newly arrived university students and then 6 and 18 months later. Other personality and family traits were also assessed. PGD reported for high school friends at the start of university and university friends 6 months later were substantially correlated (+0.60). This correlation was only slightly diminished if restricted to students whose home was greater than 50 miles from the university. PGD was strongly predicted across three cohorts by male sex (+), extraversion (+), conscientiousness (-), a family history of alcohol use disorders (+) and depression (+), and religiosity (-).These predictors of PGD had a relatively stable impact over 18 months and, aside from sex, differed only modestly in males and females. As individuals change social groups from high school to university, the level of PGD remains relatively stable, suggesting that individuals play a strong role in selecting peer groups with consistent characteristics. PGD is also predicted cross-sectionally and longitudinally by personality, family background and religiosity. Our results suggest that the association between personal and peer deviance is due at least in part to the effects of social selection.
    Social Psychiatry and Psychiatric Epidemiology 02/2015; DOI:10.1007/s00127-015-1031-4 · 2.54 Impact Factor
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    ABSTRACT: This study examined whether relocating from a high-poverty neighborhood to a lower poverty neighborhood as part of a federal housing relocation program (HOPE VI; Housing Opportunities for People Everywhere) had effects on adolescent mental and behavioral health compared to adolescents consistently living in lower poverty neighborhoods. Sociodemographic, risk behavior, and neighborhood data were collected from 592 low-income, primarily African-American adolescents and their primary caregivers. Structured psychiatric interviews were conducted with adolescents. Prerelocation neighborhood, demographic, and risk behavior data were also included. Hierarchical Linear Modeling (HLM) was used to test associations between neighborhood variables and risk outcomes. HLM was used to test whether the effect of neighborhood relocation and neighborhood characteristics might explain differences in sexual risk taking, substance use, and mental health outcomes. Adolescents who relocated of HOPE VI neighborhoods (n = 158) fared worse than control group participants (n = 429) on most self-reported mental health outcomes. The addition of subjective neighborhood measures generally did not substantively change these results. Our findings suggest that moving from a high-poverty neighborhood to a somewhat lower poverty neighborhood is not associated with better mental health and risk behavior outcomes in adolescents. The continued effects of having grown up in a high-poverty neighborhood, the small improvements in their new neighborhoods, the comparatively short length of time they lived in their new neighborhood, and/or the stress of moving appears to worsen most of the mental health outcomes of HOPE VI compared to control group participants who consistently lived in the lower poverty neighborhoods. © 2015 Association for Child and Adolescent Mental Health.
    Journal of Child Psychology and Psychiatry 02/2015; DOI:10.1111/jcpp.12386 · 6.46 Impact Factor
  • Danielle M. Dick
    Psychological Medicine 02/2015; 45(03):671. DOI:10.1017/S0033291714002621 · 5.94 Impact Factor
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    ABSTRACT: We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants' risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention.
    Development and Psychopathology 02/2015; 27(1):81-95. DOI:10.1017/S095457941400131X · 4.89 Impact Factor
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    ABSTRACT: Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.
    Perspectives on Psychological Science 01/2015; 10(1):37-59. DOI:10.1177/1745691614556682 · 4.89 Impact Factor

Publication Stats

7k Citations
947.15 Total Impact Points


  • 2008–2015
    • Virginia Commonwealth University
      • • Virginia Institute for Psychiatric and Behavioral Genetics
      • • Department of Psychiatry
      Ричмонд, Virginia, United States
    • University of Jyväskylä
      • Department of Psychology
      Jyväskylä, Province of Western Finland, Finland
    • Washington School of Psychiatry
      Washington, Washington, D.C., United States
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2004–2012
    • Washington University in St. Louis
      • • Department of Psychiatry
      • • Department of Psychology
      San Luis, Missouri, United States
  • 2010
    • University of Amsterdam
      • Department of Education
      Amsterdamo, North Holland, Netherlands
  • 2002–2008
    • Indiana University-Purdue University Indianapolis
      • Department of Medical and Molecular Genetics
      Indianapolis, Indiana, United States
    • University of Iowa
      • Department of Psychiatry
      Iowa City, Iowa, United States
  • 2007
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, California, 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
    • University of Helsinki
      • Department of Dental Public Health
      Helsinki, Uusimaa, Finland
    • Indiana University Health
      Bloomington, Indiana, United States