Waldman Lab Research Topics
(* graduate student author; + postdoctoral fellow author; ^ undergraduate student author)
1. Using Genome-Wide Data to Find Genes for Externalizing Psychopathology, including Attention Deficit Hyperactivity Disorder, Conduct Disorder, Aggression, Psychopathic Traits, and Antisocial Behavior
Over the past decade, technological and statistical advances have made it possible to economically and efficiently genotype large samples and to test millions of genetic markers for association with traits and disorders. We are using genome-wide data from our own sample and other samples in a series of collaborative studies to conduct genome-wide association scans (GWAS) of various forms of Externalizing Psychopathology, including Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Aggression, Psychopathic Traits, and Antisocial Behavior. Across these GWAS projects we are particularly interested in the use of gene-based tests and multivariate analyses to increase power and the likelihood of finding replicable associations, as well as exploring similarities and differences in genetic risk factors across different ethnic groups.
• With regard to ADHD, I am part of the Psychiatric Genetics Consortium (PGC) ADHD workgroup and we currently have 12 genome-wide significant loci and a forthcoming paper on this that is currently in preparation.
• For Conduct Disorder, I am co-leading a GWAS of ODD+CD diagnoses in the PGC ADHD plus Danish iPsych samples. I am also leading a GWAS of Conduct Disorder symptoms - and symptoms of the Aggressive and Rule-Breaking CD factors - in the Yale-Penn and SAGE multi-site samples recruited for substance use and abuse. Across the two samples we have ~5000 European-American and ~5000 African-American participants and are in the process of expanding the number of samples.
• For psychopathic traits, we've conducted a GWAS in the TEDS sample in the UK and will be trying to replicate the top associations in my sample here in Georgia, as well as trying to find other youth samples with both GWAS genotypes and similar measures of psychopathic traits.
• And finally, I am part of the BROAD collaboration on GWAS of antisocial behavior broadly construed co-led by Danielle Posthuma and Sarah Medland.
Relevant Publications: In progress.
Bralten* J, Franke B, Waldman ID, Rommelse N, Hartman C, Asherson P, Banaschewski T, Ebstein RP, Gill M, Miranda A, Oades RD, Roeyers H, Rothenberger A, Sergeant JA, Oosterlaan J, Sonuga-Barke E,
Steinhausen H-C, Faraone SV, Buitelaar JK, Arias-Vásquez A (2013). Candidate Genetic Pathways for Attention-Deficit/Hyperactivity Disorder (ADHD) Show Association to Hyperactive/Impulsive Symptoms in Children With ADHD Journal of the American Academy of Child & Adolescent Psychiatry, 52, 1204-1212.
2. Tests of Specific Genes as Risk Factors for Externalizing Psychopathology
In addition to genome-wide studies, we have conducted and are conducting studies that focus on the association of specific genes with various forms of Externalizing Psychopathology, including Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, Aggression,
Psychopathic Traits, and Antisocial Behavior. These genes are chosen based on neurobiological findings in humans and animal models for the biological plausibility of their etiological role in these traits and disorders. These projects include:
a. Association of the Oxytocin Receptor gene with Autism, Aggression, and Social Behavior Relevant Publications:
*LoParo, D., Johansson, A., +Walum, H., Westberg, L., Santtila, P., & Waldman, I.D. (2015). Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. *LoParo, D. & Waldman, I.D. (2014). The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Molecular Psychiatry, 20, 640-646.
*Feng, C., Lori, A., Waldman, I.D., Binder, E., Haroon, E., Rilling, J. (2016). A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans. Genes, Brain & Behavior, 14, 516-525.
+Walum, H. Waldman, I.D., & Young, L. (2016). Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biological Psychiatry, 79, 251-257.
*Michalska, K. J., Decety, J., Liu, C., Chen, Q., Martz, M.E., Jacob, S., Hipwell, A. E., Lee, S.S., Chronis-Tuscano, A., Waldman, I. D., & Lahey, B. B., (2014). Genetic Imaging of the Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Positive Maternal Parenting. Frontiers in Behavioral Neuroscience, 8, 1-10.
*Johansson, A., Bergman, H., Corander, J., Waldman, I., Karrani, N., Salo, B., Jern, P., Ålgars, M.,
Sandnabba, K., Santtila, P., & Westberg, L. (2012). Alcohol and aggressive behavior in men - moderating effects of oxytocin receptor gene (OXTR) polymorphisms. Genes, Brain and Behavior, 11, 214-221. b. Finding Dopamine & Noradrenergic Genetic Risk Factors for ADHD
Relevant Publications:
Rowe, D.C., Stever, C , Giedinghagen, L.N., Gard, J.M.C., Cleveland, H.H., Terris^, S.T., *Mohr, J.H., Sherman, S.L., Abramowitz, A., & Waldman, I.D. (1998). Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder. Molecular Psychiatry, 3, 419-426.
Waldman, I.D., Rowe, D.C., Abramowitz, A., ^ Kozel, S.T., *Mohr, J.H., Sherman, S.L., Cleveland, H.H., Sanders, M.L., & Stever, C. (1998). Association and linkage of the dopamine transporter gene (DAT1) and Attention Deficit Hyperactivity Disorder in children. American Journal of Human Genetics, 63, 1767-1776.
*Tahir, E., Yazgan, Y., Cirakoglu, B., Ozbay, F., Waldman, I.D., & Asherson, P.J. (2000). Association and linkage of DRD4 and DRD5 with Attention Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. Molecular Psychiatry, 5, 396-404
(2002). Dopaminergic system genes in ADHD: Towards a biological hypothesis. Neuropsychopharmacology, 27, 607-619.
Kim, C-H., Hahn, M.K., Joung, Y., Steele, A.H., Cohen, B.M., Robertson, D., *Gizer, I., Waldman, I.D., Blakely, R.D., & Kim, K-S. (2006). A Novel Polymorphism in the Human Norepinephrine Transporter Gene Alters Promoter Activity and is Associated with Attention Deficit Hyperactivity Disorder. Proceedings of the National Academy of Sciences, 103, 19164-19169.
3. Meta-Analyses of Genetic and Environmental Influences on ADHD and Antisocial Behavior
Meta-Analysis is a quantitative approach to reviewing the findings in a research literature that bear on a particular question or a set of hypotheses. Using meta-analytic methods allows one to characterize the overall effect size (i.e., the magnitude of an association) and its statistical significance, characterize the precision of that effect size and its heterogeneity across studies, and assess the role of substantive and methodological variables as moderators that may help explain some of the cross-study heterogeneity. We have used meta-analyses to summarize the evidence for genetic and environmental Influences on ADHD and Antisocial Behavior.
Relevant Publications:
*Rhee, S.H. & Waldman, I.D. (2002). Genetic and environmental influences on antisocial behavior: A meta-analysis of twin and adoption studies. Psychological Bulletin, 128, 490-529.
*Gizer, I.R., *Ficks, C.A., & Waldman, I.D. (2009). Candidate gene studies of ADHD: a meta-analytic review. Human Genetics, 126, 51-90.
*Ficks, C.A. & Waldman, I.D. (2014). Candidate Genes for Aggression and Antisocial Behavior: A Meta-analysis of Association Studies of the 5HTTLPR and MAOA-uVNTR. Behavior Genetics, 44, 427-444. 4. Analyses of the Classification and Underlying Structure of Youth Psychiatric Disorders
Despite decades of research, uncertainty remains regarding the valid classification and underlying structure of psychiatric disorders in children and adolescents. Using data from several large population-based twin samples we are conducting sophisticated latent variable modeling and multivariate behavior genetic analyses in an effort to elucidate the underlying structure of both internalizing and externalizing disorders. In our recent efforts in this area we use twin study designs and sophisticated statistical methods to test alternative models for the hierarchical dimensional structure of psychopathology. Relevant Publications:
Lahey, B.B., Applegate, B., McBurnett, K., Biederman, J., Greenhill, L., Hynd, G.W., Barkley, R.A.,
Newcorn, J., Jensen, P., Richters, J., Garfinkel, B., Kerdyk, L., Frick, P.J., Ollendick, T., Perez, D., Hart, E.L., Waldman, I., & Shaffer, D. (1994). DSM-IV field trials for attention-deficit / hyperactivity disorder in children and adolescents. American Journal of Psychiatry, 151,1673-1685.
Lahey, B.B., Applegate, B., Barkley, R.A., Garfinkel, B., McBurnett, K.,Kerdyk, L., Greenhill, L., Hynd, G.W., Frick, P.J., Newcorn, J., Biederman, J., Ollendick, T., Hart, E.L., Perez, D., Waldman, I., & Shaffer, D. (1994). DSM-IV field trials for oppositional defiant disorder and conduct disorder in children and
adolescents. American Journal of Psychiatry, 151, 1163-1171.
Lahey, B. B., Applegate, B., Waldman, I. D., Loft, J., Hankin, B. L., & Rick, J. (2004). The structure of child and adolescent psychopathology: Generating new hypotheses. Journal of Abnormal Psychology, 113, 358-385.
Lahey, B. B., Rathouz, P. J., Applegate, B., Van Hulle, C. A., Garriock, H. A., Urbano, R. C., Chapman, D. A., Krueger, R. F., & Waldman, I. D. (2008). Testing structural models of DSM-IV symptoms of common forms of child and adolescent psychopathology. Journal of Abnormal Child Psychology, 36, 187-206. Lahey, B. B., Van Hulle, C. A., *Singh, A. L., Waldman, I. D., & Rathouz, P. J. (2011). Higher-Order Genetic and Environmental Structure of Prevalent Forms of Child and Adolescent Psychopathology. Archives of General Psychiatry, 68, 181-189. PMID:21300945
*Rhee, S.H., Lahey, B.B., & Waldman, I.D. (2015). Comorbidity Among Dimensions of
Childhood Psychopathology: Converging Evidence From Behavior Genetics. Child Development Perspectives.
Waldman, I. D., *Poore, H.E., van Hulle, C.A., Rathouz, P. J., & Lahey, B.B. (in press). External Validity of a Hierarchical Dimensional Model of Child and Adolescent Psychopathology: Tests Using Confirmatory Factor Analyses and Multivariate Behavior Genetic Analyses. Journal of Abnormal Psychology.
Lahey, B. B., Krueger, R. F., Rathouz, P. J., Waldman, I. D., & Zald, D. H. (in press). A hierarchical causal taxonomy of psychopathology across the life span. Psychological Bulletin.
Lahey, B. B., Krueger, R. F., Rathouz, P. J., Waldman, I. D., & Zald, D. H. (in press). Perspective: Validity and utility of the general factor of psychopathology. World Psychiatry.
5. Etiological Relation of Temperament and Personality with Youth Psychiatric Disorders Contemporary approaches to characterizing psychopathology have emphasized the continuities between normal range function and the abnormal extreme of various quantitative dimensions in contrast to qualitative distinctions among categorical diagnoses. Along these lines we have used multivariate behavior genetic analyses to examine the etiological role of various temperament and personality dimensions in general, internalizing, and externalizing dimensions of psychopathology. Relevant Publications:
Rhee, Soo Hyun; Friedman, Naomi P.; Corley, Robin P.; Hewitt, John K.; Hink, Laura K.; Johnson, Daniel P.; Smith Watts, Ashley K.; Young, Susan E.; Robinson, JoAnn; Waldman, Irwin D.; Zahn-Waxler, Carolyn. (2016). An Examination of the Developmental Propensity Model of Conduct Problems. Journal of Abnormal Psychology.
Tackett, J. L., Lahey, B. B, Van Hulle, C., Waldman, I. D., Krueger, R. F., & Rathouz, P. J. (2013). Common genetic influences on negative emotionality and a general psychopathology factor in childhood and adolescence. Journal of Abnormal Psychology, 122, 1142-1153.
*Hink, L. K., Rhee, S. H., Corley, R.P., Cosgrove, V. E., Hewitt, J. K., Schulz-Heik, R. J., Lahey, B.B., & Waldman, I.D. (2013). Personality Dimensions as Common and Broadband-Specific Features for Internalizing and Externalizing Disorders. Journal of Abnormal Child Psychology, 41, 939-957. Waldman, I.D., Tackett, J.L., Van Hulle, C.A., Applegate, B., Pardini, D., Frick, P.J., & Lahey B.B. (2011). Child and adolescent conduct disorder substantially shares genetic influences with three socioemotional
dispositions. Journal of Abnormal Psychology, 120, 57-70. PMID:21142331.
Tackett, J.L., Waldman, I.D., Van Hulle, C.A., & Lahey, B.B. (2011). Shared Genetic Influences on Negative Emotionality and Major Depression/Conduct Disorder Comorbidity. Journal of the American Academy of Child and Adolescent Psychiatry, 50, 818-827.
*Singh, A.L. & Waldman, I.D. (2010). The Etiology of Associations between Negative Emotionality and Childhood Externalizing Disorders. Journal of Abnormal Psychology, 119, 376-88.
6. Neurocognitive and Social Cognitive Endophenotypes for ADHD and Aggression
Within the context of behavioral and molecular genetic designs, we have examined social cognitive and neurocognitive executive function measures that are putative endophenotypes for ADHD and
aggression. These constructs represent specific psychological mechanisms that are posited to underlie the etiology of these disorders and traits and may be influenced by the specific genes that are risk factors for these conditions. Specifically, we are interested in the role of children's inattention, impulsivity, hostile perceptual biases, and deficits and biases in the processing of facial emotions and others’ intentions in the development of aggression and psychopathic traits, and have examined these and related constructs as endophenotypes for childhood disruptive disorders.
Relevant Publications:
Waldman, I.D. (1996). Aggressive children's hostile perceptual and reponse biases: The role of attention and impulsivity. Child Development, 67, 1015-1033.
Waldman, I.D. (2005). Statistical Approaches to Complex Phenotypes: Evaluating Neuropsychological Endophenotypes for ADHD. Biological Psychiatry, 57, 1347-1356.
Waldman, I.D., Nigg, J.T., *Gizer, I.R., Park, L., Rappley, M., and Friderici, K. (2006). The Adrenergic Receptor 2-a Gene (ADRA2a) and Neuropsychological Executive Functions as Putative Endophenotypes for Childhood ADHD. Cognitive, Affective, and Behavioral Neuroscience, 6, 18-30.
*Gizer, I.R. & Waldman, I.D. (2012). Double Dissociation between Lab Measures of Inattention and Impulsivity and the Dopamine Transporter Gene (DAT1) and Dopamine D4 Receptor
Gene (DRD4). Journal of Abnormal Psychology, 121, 1011-1023.
*Park, Y. & Waldman, I.D. (2014). Influence of the COMT val 108/158 met polymorphism on continuous performance task indices. Neuropsychologia, 61, 45-55.
McGrath LM, Braaten EB, Doty ND, Willoughby BL, Wilson HK, O’Donnell EH, Colvin MK, Ditmars HL, Blais JE, Hill EN, Metzger A, Perlis RH, Willcutt EG, Smoller JW, Waldman ID, Faraone SV, Seidman LJ, & Doyle AE. (in press). Extending the 'cross-disorder' relevance of executive functions to dimensional neuropsychiatric traits in youth. Journal of Child Psychology and Psychiatry.
7. Rigorous Tests of Direct Causal Environmental Influences on Child Psychopathology
Traditional approaches to examining putative environmental influences on child psychopathology have relied on simple associations between disorders and variables thought to reflect environmental risk factors. Unfortunately, such associations may reflect background genetic or shared environmental influences rather than the direct causal influences of the “environmental” variables themselves. Over the past decade, in collaboration with a set of colleagues, we have rigorously examined specific
environmental influences for conduct problems and ADHD. Specifically, in a large genetically-informative national representative sample of mothers and their children (i.e., the Children of the National
Longitudinal Study of Youth, or CNLSY) as well as in 2 large twin samples, we have conducted both between-family and within-family tests of the effects of several putative environmental risk factors, including mother’s smoking and drinking during pregnancy, mother’s age at the birth of each child, neighborhood effects, effects of family income, and birth weight and gestational age.
Relevant Publications:
D’Onofrio, B. M., Van Hulle, C. A., Waldman, I. D., Rodgers, J. L., Rathouz, P. J., & Lahey, B. B. (2007). Causal inferences regarding prenatal alcohol exposure and childhood externalizing problems. Archives of General Psychiatry, 64, 1296-1304.
Lahey BB, Van Hulle CA, D'Onofrio BM, Rodgers JL, Waldman ID. (2008). Is Parental Knowledge of their Adolescent Offspring's Whereabouts and Peer Associations Spuriously Associated with Offspring Delinquency? Journal of Abnormal Child Psychology , 36, 807-23.
D'Onofrio, B. M., Van Hulle, C. A., Waldman, I. D., Rodgers, J. L., Harden, K. P., Rathouz, P. J., & Lahey, B. B. (2008). Smoking during pregnancy and offspring externalizing problems: An exploration of genetic and environmental confounds. Development and Psychopathology, 20, 139-164.
Harden, K. P., D'Onofrio, B. M., Van Hulle, C. A., Turkheimer, E., Rodgers, J. L.,, Waldman, I.D., & Lahey, B. B. (2009). Population density and youth antisocial behavior. Journal of Abnormal Child Psychology, 50, 999-1008.
D'Onofrio, B.M., Goodnight, J., Van Hulle, C.A., Waldman, I.D., Rodgers, J.L., Rathouz, P.J., Lahey, B.B. (2009). A quasi-experimental analysis of the association between family income and offspring conduct problems. Journal of Abnormal Child Psychology, 37, 415-429.
D'Onofrio, B.M., Goodnight, J., Van Hulle, C.A., Waldman, I.D., Rodgers, J.L., Rathouz, P.J., Lahey,
B.B. (2009). Maternal age at childbirth and offspring disruptive behaviors: Testing the causal hypothesis. Journal of Child Psychology and Psychiatry, 50, 1018-1028.
Goodnight, J.A., Lahey, B.B., Van Hulle, C.A., Rodgers, J.L., Rathouz, P.J., Waldman, I.D., & D'Onofrio, B.M. (2012). A quasi-experimental analysis of the influence of neighborhood disadvantage on child and adolescent conduct problems. Journal of Abnormal Psychology, 121, 95-108.
*Sujan, A.C., Rickert, M.E., Class, Q.A., Coyne, C.A., Lichtenstein, P., Almqvist, C., Larsson, H., Sjölander, A., Lahey, B.B., van Hulle, C., Waldman, I., Oberg, S.A. & D’Onofrio, B.M. (in press). A genetically informed study of the associations between maternal age at childbearing and adverse perinatal outcomes. Behavior Genetics.
8. Exploration of Issues Related to Replicability of Findings of Psychological Research
In addition to testing for replication of behavioral and molecular genetic findings using meta-analysis, I've recently co-authored or edited several pieces focusing explicitly on replication issues in our field. Relevant Publications:
+Walum, H. Waldman, I.D., & Young, L. (2016). Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biological Psychiatry, 79, 251-257.
Waldman, I.D. & Lilienfeld, S.O. (in press). Thinking About Data, Research Methods, and Statistical Analyses: Commentary on Sijtsma’s (2014) “Playing with Data”. Psychometrika.
Lilienfeld, S.O. & Waldman, I.D. (in press). Psychological Science Under Scrutiny. New York: Wiley.
