Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.

Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.

The general psychopathology factor (p) from adolescence to adulthood: Exploring the developmental trajectories of p using a multi-method approach.

Considerable attention has been directed towards studying co-occurring psychopathology through the lens of a general factor (p-factor). However, the developmental trajectory and stability of the p-factor have yet to be fully understood. The present study examined the explanatory power of dynamic mutualism theory - an alternative framework that suggests the p-factor is a product of lower-level symptom interactions that strengthen throughout development. Data were drawn from a population-based sample of girls (N = 2450) who reported on the severity of internalizing and externalizing problems each year from age 14 to age 21. Predictions of dynamic mutualism were tested using three distinct complementary statistical approaches including: longitudinal bifactor models, random-intercept cross-lagged panel models (RI-CLPMs), and network models. Across methods, study results document preliminary support for mutualistic processes in the development of co-occurring psychopathology (that is captured in p). Findings emphasize the importance of exploring alternative frameworks and methods for better understanding the p-factor and its development.

Les progrès dans la réalisation de la classification quantitative de la psychopathologie.

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 generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

Familial factors and the risk of borderline personality pathology: genetic and environmental transmission.

BACKGROUND: Parental characteristics and practices predict borderline personality disorder (BPD) symptoms in children. However, it is difficult to disentangle whether these effects are genetically or environmentally mediated. The present study examines the contributions of genetic and environmental influences by comparing the effects of familial risk factors (i.e. parental psychopathology and borderline traits, maladaptive parenting, marital discord) on child BPD traits in genetically related (biological) and non-related (adoptive) families. METHODS: Data are from 409 adoptive and 208 biological families who participated in the Siblings Interaction and Behavior Study (SIBS) and 580 twin families the Minnesota Twin Family Study (MTFS). Parent characteristics and practices included parental psychopathology (measured via structured clinical interviews), parental BPD traits, parenting behaviors, and marital discord. A series of multi-level regression models were estimated to examine the relationship of familial risk factors to child BPD traits and to test whether children's adoptive status moderated the association. RESULTS: Symptom counts of parents' conduct disorder, adult antisocial behavior, nicotine, alcohol, and illicit drug dependence, and paternal BPD traits substantially predicted child BPD traits only in biological offspring, implying genetic transmission. Maternal BPD traits and both maternal and paternal conflict, lack of regard, and lack of involvement predicted offspring BPD traits regardless of the adoptive status, implying environmental transmission. CONCLUSIONS: Parental externalizing psychopathology and father's BPD traits contribute genetic risk for offspring BPD traits, but mothers' BPD traits and parents' poor parenting constitute environmental risks for the development of these offspring traits.

Genetic and environmental influences on the codevelopment among borderline personality disorder traits, major depression symptoms, and substance use disorder symptoms from adolescence to young adulthood.

Although borderline personality disorder (BPD) traits decline from adolescence to adulthood, comorbid psychopathology such as symptoms of major depressive disorder (MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt this normative decline. Using a longitudinal sample of female twins (N = 1,763), we examined if levels of BPD traits were correlated with changes in MDD, AUD, and DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model examined the contributions of genetic and environmental factors to the relationships between developmental components of these phenotypes. Higher BPD trait levels predicted a greater rate of increase in AUD and DUD symptoms, and higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from ages 14 to 24. Common genetic influences accounted for the associations between BPD traits and each disorder, as well as the interrelationships of AUD and DUD symptoms. Both genetic and nonshared environmental influences accounted for the correlated levels between BPD traits and MDD symptoms, but solely environmental influences accounted for the correlated changes between the two over time. Results indicate that higher levels of BPD traits may contribute to an earlier onset and faster escalation of AUD and DUD symptoms, and substance use problems slow the normative decline in BPD traits. Overall, our data suggests that primarily genetic influences contribute to the comorbidity between BPD features and substance use disorder symptoms. We discuss our data in the context of two major theories of developmental psychopathology and comorbidity.

The developmental progression of age 14 behavioral disinhibition, early age of sexual initiation, and subsequent sexual risk-taking behavior.

BACKGROUND: Research has demonstrated a consistent relationship between early sexual experience and subsequent sexual risk-taking behaviors. We hypothesized that this relationship is due to a general predisposition toward behavioral disinhibition (BD), and that relationships among BD, early sex, and subsequent risky sexual behavior may be influenced by common genetic influences for males and common environmental influences for females. METHODS: A prospective sample of 1,512 same-sex adolescent twins (50.2% female) was used. Adolescent BD was measured by clinical symptom counts of conduct disorder, oppositional defiant disorder, and self-reported delinquent behavior (age 14). Age of sexual initiation was defined as first age of consensual oral or penetrative sex (mean age ~17). Adult risky sexual behavior was defined by sexual behaviors under the influence of drugs and alcohol and number of casual sexual partners in the past year (age 24). RESULTS: Multivariate analyses showed evidence for substantial common genetic variance among age 14 BD, age at sexual initiation, and adult risky sexual behavior for males, but not females. There was no significant difference in the degree of common environmental influence on these variables for females compared to males. Notably, age of sexual initiation was not significantly correlated with age 24 risky sexual behavior for females. CONCLUSION: The relationship between early sex and later risky sex can be better understood through a general liability toward BD, which is influenced primarily by genetic factors for males. The association between age 14 BD and age of sexual initiation was influenced through a combination of genetic and environmental factors for females; however, age of sexual initiation does not appear to be a salient predictor of adult women's sexual risk-taking behavior. Findings suggest that prevention programs aimed at reducing sexual risk behavior might target youth exhibiting BD by age 14, particularly males. More research is needed on what predicts adult sexual risk-taking behavior for females.

Symptoms of borderline personality and related pathologies behave as temporal and contemporaneous networks.

In contrast to latent variable models suggesting a common etiology, network theory proposes that symptoms of psychopathology co-occur because of direct, dynamic associations among them. We examined how symptoms associated with borderline personality disorder, depression, and anxiety mutually reinforce one another over time, forming a network. We further identified symptoms that drove the network by exerting the most influence on other symptoms. Participants were 37 undergraduate students aged 18 to 26. Following baseline assessment, participants were prompted to answer a Qualtrics-based survey of current symptoms of BPD, depression, and anxiety twice daily for 40 days. Multilevel time-series network analyses were conducted with (a) BPD symptoms alone and (b) BPD, depressive and anxiety symptoms. In the network of BPD symptoms, momentary interpersonal difficulties predicted later dissociation, which predicted later affective fluctuation at the within-person level. Dissociation exerted the strongest influence on the overall symptom network. When depressive and anxiety symptoms were included, the networks identified several cross-disorder connections, such as anhedonia and feeling tense, which highlight potential pathways that describe the comorbidity of BPD with anxiety and depressive syndromes. Overall, cognitive symptoms and dissociation were identified as the most influential symptoms across the networks. This study indicates that BPD, depression, and anxiety symptoms may mutually reinforce one another concurrently and over time. Cognitive symptoms exert the highest influence on the cross-disorder networks, such that they influence BPD, depressive, and anxiety symptoms. Our results support the need of targeting cognitions in the treatment of comorbid BPD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Direct Effects of Cannabis Intoxication on Motivations for Softer and Harder Drug Use: An Experimental Approach to the Gateway Hypothesis.

Aims: This study experimentally tested whether there is a gateway-type effect of cannabis administration on tobacco and cocaine motivation and whether motivational responses predicted use 6 months later. Methods: A 2 (condition: active cannabis vs. placebo joint)×3 (substance stimulus type: tobacco, cannabis, and cocaine) factor within-subjects design for both implicit and explicit motivation. Both experimental sessions were conducted in a cannabis dispensary ("coffeeshop") in Amsterdam and were separated by ∼1 week, followed by a 6-month online follow-up. Eighty-five participants between 18 and 27 years of age (57% male), who used cannabis, tobacco, and cocaine <15 times per month, participated in session 1 (session 2: N=79 and follow-up: N=81). Counterbalanced over sessions, participants smoked an active and a placebo joint following a paced puffing procedure. Before and after smoking, craving and avoidance (explicit motivation) were assessed using visual analog scales, and after smoking, the stimulus response compatibility test was completed to assess approach biases (implicit motivation). Self-reported intoxication and similarity to their usual smoking experience were assessed at the end of both sessions. Self-reported frequency/quantity and dependence symptoms for tobacco, cannabis, and cocaine were assessed at all time points. A linear mixed model approach was used to assess the effects of condition, substance stimulus type, and their interactions on explicit and implicit motivation. Results: In the active condition, participants reported higher levels of intoxication and an experience more similar to their usual smoking experience than in the placebo condition. There was no significant effect of condition, substance type, or their interaction on approach bias. Participants exhibited increased cannabis craving during the placebo condition only and increased explicit cannabis avoidance during the active condition only. Explicit tobacco avoidance decreased during both conditions. Baseline measures did not predict use at 6-month follow-up. Conclusions: In light users, cannabis intoxication did not affect implicit and explicit tobacco or cocaine motivations. Tobacco avoidance decreased regardless of condition, indicating that the cannabis cue-rich setting-rather than tetrahydrocannabinol itself-may momentarily increase the likelihood to smoke tobacco. However, motivation at baseline did not predict use 6 months later, deeming any gateway-like function unlikely.

Mutualistic processes in the development of psychopathology: The special case of borderline personality disorder.

Borderline personality disorder (BPD) is a serious mental illness characterized by instability in affective, cognitive, and interpersonal domains. BPD co-occurs with several mental disorders and has robust, positive associations with the general factors of psychopathology (p-factor) and personality disorders (g-PD). Consequently, some researchers have purported BPD to be a marker of p, such that the core features of BPD reflect a generalized liability to psychopathology. This assertion has largely stemmed from cross-sectional evidence and no research to date has explicated the developmental relationships between BPD and p. The present study aimed to investigate the development of BPD traits and the p-factor by examining predictions of two opposing frameworks: dynamic mutualism theory and the common cause theory. Competing theories were evaluated to determine which perspective best accounted for the relationship of BPD and p from adolescence into young adulthood. Data were drawn from the Pittsburgh Girls Study (PGS; N = 2,450) and included yearly self-assessments of BPD and other internalizing and externalizing indices from ages 14 to 21. Theories were examined using random-intercept cross-lagged panel models (RI-CLPMs) and network models. Results indicated that neither dynamic mutualism nor the common cause theory could fully explain the developmental relations between BPD and p. Instead, both frameworks were partially supported, with p found to strongly predict within-person change in BPD at several ages. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Group exposure therapy treatment for post-traumatic stress disorder in female veterans.

OBJECTIVES: The purpose of this study was to examine the application of a group exposure therapy model, the content of which consisted solely of repeated imaginal exposure during sessions, in a clinical sample of female veterans with post-traumatic stress disorder (PTSD). Establishing group delivery of exposure therapy will expand options, increase efficiency, and introduce group curative factors. METHODS: Eighty-eight female veterans with PTSD completed a six-session exposure group, three participants per group, as a component of a larger treatment program. The PTSD symptom checklist (PCL) was used as the outcome measure and administered in each session. RESULTS: Pre/post-paired t-tests showed significant improvement in PTSD on the PCL, with 40% of completers showing at least a 10-point drop in the PCL scores. In addition, a repeated measures analysis of variance showed a significant main effect and a significant quadratic equation, with expected initial increases in the PCL followed by a decrease below baseline at session 6. CONCLUSIONS: The group exposure treatment protocol showed positive outcomes on PTSD symptoms in a real-world clinical sample of female veterans. The implications include an expansion of exposure treatment choices for veterans with PTSD and increased options for therapists.

Two Filtering Methods of Forecasting Linear and Nonlinear Dynamics of Intensive Longitudinal Data.

With the advent of new data collection technologies, intensive longitudinal data (ILD) are collected more frequently than ever. Along with the increased prevalence of ILD, more methods are being developed to analyze these data. However, relatively few methods have yet been applied for making long- or even short-term predictions from ILD in behavioral settings. Applications of forecasting methods to behavioral ILD are still scant. We first establish a general framework for modeling ILD and then extend that frame to two previously existing forecasting methods: these methods are Kalman prediction and ensemble prediction. After implementing Kalman and ensemble forecasts in free and open-source software, we apply these methods to daily drug and alcohol use data. In doing so, we create a simple, but nonlinear dynamical system model of daily drug and alcohol use and illustrate important differences between the forecasting methods. We further compare the Kalman and ensemble forecasting methods to several simpler forecasts of daily drug and alcohol use. Ensemble forecasts may be more appropriate than Kalman forecasts for nonlinear dynamical systems models, but further forecasting evaluation methods must be put into practice.

HiTOP Assessment of Externalizing Antagonism and Disinhibition.

This article outlines the Phase 1 efforts of the HiTOP Measure Development group for externalizing constructs, which include disinhibited externalizing, antagonistic externalizing, attention deficit hyperactivity disorder, substance use, and externalizing/maladaptive behaviors. We provide background on the constructs included and the process and issues involved in developing a measure for this diverse range of psychopathology symptoms, traits, and behaviors.

Testing the role of adolescent sexual initiation in later-life sexual risk behavior: a longitudinal twin design.

The consistent association between adolescent sexual initiation (ASI) and risky adult sexual behavior (RASB) has generally been assumed to indicate that ASI has a causal effect on RASB; consequently, it is assumed that delaying ASI will reduce RASB. Yet the ASI-RASB association might be better accounted for by some third variable. We evaluated the causal role of ASI (initiation of oral, anal, or vaginal sex at or before age 16) in influencing RASB in a longitudinal sample of 2,173 twins (followed from ages 11 to 24 or from ages 17 to 29) using two methods: the discordant-twin design and the propensity-score design. The former controlled for unmeasured genetic and shared environmental factors, and the latter controlled for measured nonshared environmental factors. We replicated the link between ASI and RASB reported in previous research, but results from the discordant-twin and propensity-score analyses suggested that this association is better explained by common genetic or environmental risk factors than as a causal effect. These findings suggest that preventing ASI is unlikely to reduce RASB.

Distress tolerance moderates the relationship between negative affect intensity with borderline personality disorder levels.

A number of studies have suggested that negative emotionality and negative affect intensity play key roles in the development and maintenance of borderline personality disorder (BPD). However, more recent research indicates that one's response to affective discomfort may be an even more important variable in the pathogenesis of BPD than either negative emotionality or negative affect intensity per se. As such, the current study aimed to empirically test the moderating role of 2 well-validated laboratory measures of the ability to tolerate psychological distress (distress tolerance) in the relationship of negative emotionality and negative affect intensity with BPD levels. Results provide laboratory-based evidence for a moderating effect of distress tolerance on the relationship of negative emotionality and negative affect intensity with levels of BPD. Specifically, the 2 former variables were related to levels of BPD among those with low distress tolerance. The current results add support to existing developmental frameworks of BPD and suggest the importance of modifying one's response to affective distress along with levels of negative emotionality in treatment settings.

Comorbidity in borderline personality: understanding dynamics in development.

Borderline personality disorder is marked by high levels of comorbidity in both adolescent and adult populations. However, the mechanisms involved in the development of comorbidity in BPD remain unclear. To address this issue, the current paper proposes the use of dynamic mutualism theory as a valuable and underexplored framework for investigating comorbidity in BPD from a developmental perspective. Specifically, we discuss how predictions of dynamic mutualism can be extended to better understand the onset, maintenance, and interplay of BPD symptoms with other forms of psychopathology over time. Moreover, we suggest that mutualistic interactions among internalizing and externalizing features throughout early development may foster the emergence of BPD symptoms in adolescence and beyond. Next, we discuss methodological approaches for testing mutualism and review indirect evidence that supports the role of mutualistic processes in the emergence and maintenance of BPD and its comorbidities. We conclude with methodological cautions and recommendations for future studies.

Alternative model of personality disorders traits predict residential addictions treatment completion.

BACKGROUND: Among people receiving residential treatment for a substance use disorder (SUD), premature treatment termination predicts poor post-treatment outcomes. We examined the utility of the alternative model for personality disorders (AMPD) for predicting premature residential SUD treatment termination, including interactions with age and gender. METHODS: Participants (N = 374) were receiving residential treatment for SUD and enrolled in a clinical trial with two conditions: Skills for Improving Distress Intolerance (SIDI) and Supportive Counseling (NCT01741415). Participants were assessed at intake on AMPD traits using the Personality Inventory for DSM-5 (PID-5) and tracked longitudinally. After establishing gender and age measurement invariance, we used competing risk models to predict treatment completion versus premature termination using interactions of PID-5 scores with age and gender. FINDINGS: Disinhibition and Negative Emotionality domains and facets predicted premature treatment termination, particularly among younger, male participants. There were positive effects of SIDI on treatment completion for participants with high levels of domain and facet Negative Emotionality. A small proportion (≈ 12 %) of the PID-5 items showed differential item functioning by age or gender; however, the aggregate impact on test-level total scores was negligible. CONCLUSIONS: Participants (particularly young men) displaying poor self-control and emotional regulation are at risk for premature termination. These findings, together with minimal aggregate differential item functioning at the scale level, suggest that the PID-5 is a practically useful, construct-valid, non-proprietary measure, aspects of which can be used for screening in residential SUD treatment. Furthermore, among those with high negative emotionality, SIDI may be effective in preventing premature treatment termination.

Appropriate Use of Bifactor Analysis in Psychopathology Research: Appreciating Benefits and Limitations.

Co-occurrence of psychiatric disorders is well documented. Recent quantitative efforts have moved toward an understanding of this phenomenon, with the general psychopathology or p-factor model emerging as the most prominent characterization. Over the past decade, bifactor model analysis has become increasingly popular as a statistical approach to describe common/shared and unique elements in psychopathology. However, recent work has highlighted potential problems with common approaches to evaluating and interpreting bifactor models. Here, we argue that bifactor models, when properly applied and interpreted, can be useful for answering some important questions in psychology and psychiatry research. We review problems with evaluating bifactor models based on global model fit statistics. We then describe more valid approaches to evaluating bifactor models and highlight 3 types of research questions for which bifactor models are well suited to answer. We also discuss the utility and limits of bifactor applications in genetic and neurobiological research. We close by comparing advantages and disadvantages of bifactor models with other analytic approaches and note that no statistical model is a panacea to rectify limitations of the research design used to gather data.

Stability, change, and heritability of borderline personality disorder traits from adolescence to adulthood: a longitudinal twin study.

Although personality disorders are best understood in the context of lifetime development, there is a paucity of work examining their longitudinal trajectory. An understanding of the expected course and the genetic and environmental contributions to these disorders is necessary for a detailed understanding of risk processes that lead to their manifestation. The current study examined the longitudinal course and heritability of borderline personality disorder (BPD) over a period of 10 years starting in adolescence (age 14) and ending in adulthood (age 24). In doing so, we built on existing research by using a large community sample of adolescent female twins, a sensitive dimensional measure of BPD traits, an extended follow-up period, and a longitudinal twin design that allowed us to investigate the heritability of BPD traits at four discrete ages spanning midadolescence to early adulthood. Results indicated that mean-level BPD traits significantly decline from adolescence to adulthood, but rank order stability remained high. BPD traits were moderately heritable at all ages, with a slight trend for increased heritability from age 14 to age 24. A genetically informed latent growth curve model indicated that both the stability and change of BPD traits are highly influenced by genetic factors and modestly by nonshared environmental factors. Our results indicate that as is the case for other personality dimensions, trait BPD declines as individuals mature from adolescence to adulthood, and that this process is influenced in part by the same genetic factors that influence BPD trait stability.

Categorical and Dimensional Conceptions of Personality Pathology in DSM-5: Toward a Model-Based Synthesis.

Symptom-based models, typically operationalized through diagnostic interview, and trait models, typically operationalized via questionnaire inventories, reflect historically competing conceptions of personality disorder (PD). DSM-5 includes models of both types, in Sections II and III, respectively. In this study, we sought to synthesize these alternative conceptualizations by fitting bifactor models to data for both Section II PD symptoms (assessed using the SCID-II interview protocol) and dimensional traits for the six PDs retained in Section III (assessed using the Personality Inventory for DSM-5). Bifactor models fit the data effectively for all six PDs, and trait and symptom indicators both loaded appreciably on general factors reflecting cross-domain PD constructs. These results provide the basis for a principled, quantitative synthesis of categorical/interview and dimensional/self-report approaches to operationalizing and studying PDs, with considerable implications for diagnosis, research, and practice.

A test of dopamine hyper- and hyposensitivity in alcohol use.

Biases in outcome processing, mediated by the mesocortical dopaminergic (DA) system, may predict individual differences in the frequency and quantity of alcohol use. We tested the hypothesis that genetic markers associated with increased DA neurotransmission contribute to reduced neural sensitivity to costs and increased alcohol use in an undergraduate sample. We created a DA transmission score using five genetic markers related to DA transmission and assessed neural sensitivity to cost using the feedback-related negativity (FRN), an event-related potential implicated in neural outcome evaluation, on both passive evaluative and active decision-making tasks. Self-reported alcohol use was assessed using the Daily Drinking Questionnaire-Revised. Participants with a higher DA transmission score reported increased alcohol consumption and exhibited a more blunted FRN on both the passive and active tasks. While dopamine hyposensitivity is common among chronic alcohol users, these data provide preliminary evidence that hypersensitivity of the dopamine system may underlie increased alcohol use in those who have not yet developed a chronic alcohol use disorder.