Irwin Waldman

Emory University | EU · Department of Psychology

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might...

Quantitative, empirical approaches to establishing the structure of psychopathology hold promise to improve on traditional psychiatric classification systems. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a framework that summarizes the substantial and growing body of quantitative evidence on the structure of psychopathology. To achieve i...

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched a...

Clinical psychology is a young science. Despite immense growth over 100+ years, human suffering from mental health conditions remains extensive, and core scientific issues in our field continue to be the subject of ongoing debate. Clinical practice depends on the growth of our research base for elucidating etiology, systematic improvements in provi...

Much research has demonstrated that psychopathology can be described in terms of broad dimensions, representing liability for multiple psychiatric disorders. Broad spectra of psychopathology (e.g., internalizing and externalizing) are increasingly used as targets for research investigating the development, etiology, and course of psychopathology be...

Historically, researchers have proposed higher-order factors to explicate the structure of psychopathology, including Externalizing, Internalizing, Fear, Distress, Thought Disorder, and a general factor. Despite extensive research in this domain, the underlying structure of psychopathology remains unresolved. Herein, we examine several issues in ad...

Substance use disorders (SUDs) are phenotypically and genetically correlated with each other and with other psychological traits characterized by behavioral undercontrol, termed externalizing phenotypes. In this study, we used Genomic Structural Equation Modeling to explore the shared genetic architecture among six externalizing phenotypes and four...

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and...

This commentary discusses questions and misconceptions about HiTOP raised by Haeffel et al. (2021). We explain what the system classifies and why it is descriptive and atheoretical, highlighting benefits and limitations of this approach. We clarify why the system is organized according to patterns of covariation or comorbidity among signs and sympt...

Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene–environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent e...

Much research has demonstrated that psychopathology can be described in terms of broad dimensions, representing liability for multiple psychiatric disorders. Broad spectra of psychopathology (e.g., internalizing and externalizing) are increasingly used as targets for research investigating the development, etiology, and course of psychopathology be...

Authoritarianism has been the subject of scientific inquiry for nearly a century, yet the vast majority of authoritarianism research has focused on right-wing authoritarianism. In the present studies, we investigate the nature, structure, and nomological network of left-wing authoritarianism (LWA), a construct famously known as “the Loch Ness Monst...

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association an...

Importance: Characterizing whether genetic variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk, and, potentially, allows us to design more targeted prevention and interventions. Objective: Employ multivariate methods to tease apart variants associated with problematic alc...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co‐occurrence in the modal case, heterogeneity of presentation within dis­orders, and instability of diagnosis within patients. This...

Generations of psychologists have been taught that mental disorder can be carved into discrete categories, each qualitatively different from the others and from normality. This model is now outdated. A preponderance of evidence indicates that (a) individual differences in mental health (health vs. illness) are a matter of degree, not kind, and (b)...

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21566-w

Traditional diagnostic systems went beyond empirical evidence on the structure of mental health. Consequently, these diagnoses do not depict psychopathology accurately, and their validity in research and utility in clinical practice are therefore limited. The Hierarchical Taxonomy of Psychopathology (HiTOP) consortium proposed a model based on stru...

The present study compared the primary models used in research on the structure of psychopathology (i.e., correlated factor, higher-order, and bifactor models) in terms of structural validity (model fit and factor reliability), longitudinal measurement invariance, concurrent and prospective predictive validity in relation to important outcomes, and...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analy...

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is ge...

Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5...

Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotyp...

Authoritarianism has been the subject of scientific inquiry for nearly a century, yet the vast majority of authoritarianism research has focused on right-wing authoritarianism. In the present studies, we investigate the nature, structure, and nomological network of left-wing authoritarianism (LWA), a construct famously known as “the Loch Ness Monst...

Evidence suggests that the Oxytocin Receptor Gene (OXTR) influences human social cognition and behavior. OXTR has been investigated in relation to antisocial behavior, but studies examining this association have produced varying results in terms of the magnitude and significance of the association as well as which SNPs are implicated. This meta-ana...

The original version of this article inadvertently omitted the word "with" between "Polymorphisms" and "Antisocial" from the title. The title "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms Antisocial Behavior: A Meta-Analysis" should be "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior: A Meta...

The study of psychopathic traits in youth is in its nascent stages and the nature and the structure of these traits is still poorly understood. In one of the most comprehensive analyses to date of the construct validity of the widely used Antisocial Processing Screening Device (APSD), we used two independent samples of youth, one community (N = 220...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures...

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorder...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). ADHD comorbid with DBDs (ADHD+DBDs) is a complex phenotype with a risk component that can be attributed to common genetic variants. Here we report a large GWAS meta-analysis of ADHD+DBDs based on seven cohort...

We advanced several “riskier tests” of the validity of bifactor models of psychopathology, which included that the general and specific psychopathology factors should be reliable and well represented by their respective indicators and that including a general factor should improve on the correlated factor model’s external validity. We compared bifa...

Structural models of psychopathology provide dimensional alternatives to traditional categorical classification systems. Competing models, such as the bifactor and correlated factors models, are typically compared via statistical indices to assess how well each model fits the same data. However, simulation studies have found evidence for probifacto...

In a large sample of youth (N = 942, 51% female), we found support for a 3 correlated factors model of psychopathology that comprised Distress, Fears, and Externalizing factors. Distress was positively associated with Neuroticism, Fears was not associated with Big Five dimensions, and Externalizing was negatively associated with Agreeableness and C...

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is...

We advanced several “riskier tests” of the validity of bifactor models of psychopathology, which included that the p-factor and specific psychopathology factors should be reliable and well-represented by their respective indicators, and that modeling the p-factor should increase the model’s external validity. We compared bifactor and correlated fac...

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals dia...

Decades of research into the etiology of conduct disorder (CD) has yet to yield a consensus on the existence of sex differences in underlying genetic and environmental influences. This may be partly due to the failure of many previous studies to make a distinction between non-aggressive and aggressive CD symptoms or test for potential developmental...

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural eq...

Background: The developmental propensity model of antisocial behavior posits that several dispositional characteristics of children transact with the environment to influence the likelihood of learning antisocial behavior across development. Specifically, greater dispositional negative emotionality, greater daring, and lower prosociality-operation...

Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify nove...

The past several decades have witnessed a proliferation of research on the dark triad (DT), a set of traits comprising Machiavellianism, narcissism, and psychopathy. The bulk of DT research has been marked by several core assumptions, most notably that each DT construct is a monolithic entity that is clearly separable from its counterpart DT constr...

An adequate understanding of specialized terminology is a prerequisite for the mastery of core concepts across all scientific disciplines, including psychological science. In a previous article (Lilienfeld et al., 2015), we presented an annotated list of 50 widely used psychological terms that should generally be avoided, or at best used judiciousl...

This chapter summarizes issues that are inherent in genetic association studies including those related to genotyping, study design, statistical analysis, and interpretation and application of results in order to guide translation of this expanding area of research into successful health-related applications. Suggestions for current best practices...

We propose a taxonomy of psychopathology based on patterns of shared causal influences identified in a review of multivariate behavior genetic studies that distinguish genetic and environmental influences that are either common to multiple dimensions of psychopathology or unique to each dimension. At the phenotypic level, first-order dimensions are...

Three subdimensions of ODD symptoms have been proposed -angry/irritable (IR), argumentative/defiant (DF) and antagonism (AN). This study tested whether longitudinal symptom trajectories could be identified by these subdimensions. Group-based trajectory analysis was used to identify developmental trajectories of IR, DF and AN symptoms. Multi-group t...

Several recent studies of the hierarchical phenotypic structure of psychopathology have identified a General psychopathology factor in addition to the more expected specific Externalizing and Internalizing dimensions in both youth and adult samples and some have found relevant unique external correlates of this General factor. We used data from 1,5...

Previous research suggests that fussy temperament in infancy predicts risk for later antisocial behavior (ASB) in childhood and adolescence. It remains unclear, however, to what extent infant fussiness is related to later ASB through causal processes or if they both reflect the same family risk factors for ASB. The current study used two approaches...

We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also co...

Psychopathy is often associated with heightened intelligence in the eyes of clinicians and laypersons despite mixed research support for this possibility. We adopted a fine-grained approach to studying the relations among psychopathy and multiple indices of intelligence, including both cognitively based intelligence (CBI) and emotional intelligence...

The present study tested specific hypotheses advanced by the developmental propensity model of the etiology of conduct problems in the Colorado Longitudinal Twin Study, a prospective, longitudinal, genetically informative sample. High negative emotionality, low behavioral inhibition, low concern and high disregard for others, and low cognitive abil...

The most notable advancement in the field of behavioral genetics over the past decade has been the expansion of traditional behavioral genetic research to include state-of-the-art molecular genetic approaches. This chapter examines advancements in the field that have been influenced by and/or have implications for developmental psychopathology. It...

Background: Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with 'cross-disorder' relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms...

The goal of this article is to promote clear thinking and clear writing among students and teachers of psychological science by curbing terminological misinformation and confusion. To this end, we present a provisional list of 50 commonly used terms in psychology, psychiatry, and allied fields that should be avoided, or at most used sparingly and w...

Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present res...

Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on...

Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to so...

We comment on Sijtsma's (2014) thought-provoking essay on how to minimize questionable research practices (QRPs) in psychology. We agree with Sijtsma that proactive measures to decrease the risk of QRPs will ultimately be more productive than efforts to target individual researchers and their work. In particular, we concur that encouraging research...

In this article, we review evidence from recent behavior genetic studies that examined the covariance among common childhood psychopathological conditions and tested specific hypotheses regarding common and broadband-specific underlying features of childhood psychopathology. Specifically, we review the distinction between internalizing and external...

The equal environments assumption (EEA) of the twin method posits that environmental influences that are etiologically relevant to a given phenotype are no more likely to be shared by monozygotic (MZ) than dizygotic (DZ) twin pairs. One method of testing the EEA is to evaluate whether increased rearing environment similarity in MZ twin pairs compar...

The importance of irritability, as measured among the symptoms of oppositional defiant disorder (ODD), has dramatically come to the fore in recent years. New diagnostic categories rely on the distinct clinical utility of irritability, and models of psychopathology suggest it plays a key role in explaining developmental pathways within and between d...

A powerful longitudinal data source, the National Longitudinal Survey of Youth Children data, allows measurement of behavior problems (BP) within a developmental perspective linking them to menarcheal timing (MT). In a preliminary analysis, we evaluate the bivariate relationships between BP measured at different developmental periods and the timing...

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identify...

The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR...

The Continuous Performance Task (CPT) is a widely-used measure of sustained attention and impulsivity. Deficits in CPT performance have been found in several psychiatric disorders, such as Attention-Deficit/hyperactivity disorder (ADHD) and schizophrenia. Molecular genetic studies of CPT performance are currently limited and have generally revealed...

Variation in central serotonin levels due to genetic mutations or experimental modifications has been associated with the manifestation of aggression in humans and animals. Many studies have examined whether common variants in serotonergic genes are implicated in aggressive or antisocial behaviors (ASB) in human samples. The two most commonly studi...

IntroductionHypothalamic-pituitary-adrenal (HPA) axis activity is related to childhood disruptive behavior disorders and to exposure to abuse and neglect. This study explores the relationship of diurnal salivary cortisol levels with oppositional defiant disorder (ODD) and caregiver attitudes toward physical punishment among boys in Mongolia.Methods...

Objectives: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Fifty-six children and adolescents (mean age=11.7±2.2) par...

Few studies have examined the etiology of psychopathic traits in youth, and even fewer have tested whether the genetic and environmental influences underlying these traits differ for boys and girls. We tested for sex differences in the etiology of 3 trait dimensions-impulsivity, narcissism, and callous-unemotionality (CU)-previously found to underl...