How a general vulnerability for psychopathology during adolescence manifests in young adults' daily lives.

BACKGROUND: There is widespread interest in the general factor of psychopathology or 'p factor', which has been proposed to reflect vulnerability to psychopathology. We examined to what extent this 'vulnerability' is associated with dysregulations in affect and behavior that occur in daily life. As such we hoped to provide an account of how this vulnerability may be maintained. METHODS: We used data from the Tracking Adolescents' Individual Lives Survey (TRAILS; N = 2,772) collected at ages 11, 14, 16, 19, and 22 years to fit a bifactor model with a general psychopathology factor, alongside internalizing, externalizing (EXT), attention-deficit/hyperactivity, and autism spectrum problem domains. Following the fifth TRAILS assessment, a subsample of participants (n = 133, age = 22.6, 43% women) with heightened risk for psychopathology completed a 6-month daily diary protocol with one assessment each day. Using a dynamic structural equation approach, we examined to what extent mean intensity, variability, inertia, and within-day co-occurrence of EXT, anxious-tense, and depressed-withdrawn affects and behaviors were associated with general factor scores. RESULTS: Unexpectedly, higher general factor scores were not associated with higher mean intensity of any of the three types of daily negative affects and behaviors, but were associated with higher variability and less carryover (inertia) EXT affects and behaviors. CONCLUSIONS: We showed that individual differences in general factor scores do not manifest as differences in average levels of daily affects and behaviors, but instead were related to a type of EXT reactivity to the environment. Future research is necessary to investigate whether reactive irritable moods may be involved in or signal vulnerability sustained psychopathology.

Emotion-related impulsivity across transdiagnostic dimensions of psychopathology.

OBJECTIVE: Several dimensions have received attention for their potential role in explaining shared variance in transdiagnostic symptoms of psychopathology. We hypothesized emotion-related impulsivity, the trait-like tendency toward difficulty restraining responses to emotion, would relate to symptoms of psychopathology, with two separable dimensions of emotion-related impulsivity relating distinctly to internalizing and externalizing symptoms. METHOD: Across two studies, we tested hypotheses using structural equation models of emotion-related impulsivity and multiple indicators of internalizing, externalizing, and thought symptoms. RESULTS: In Study 1 (658 undergraduates), emotion-related impulsivity was highly correlated with the general psychopathology (p) factor. In study 2 (421 Mechanical Turk participants), models did not support a general p factor; however, we replicated the hypothesized associations of emotion-related impulsivity dimensions with internalizing and externalizing factors. Across both studies, forms of emotion-related impulsivity uniquely and differentially related to internalizing and externalizing symptoms. CONCLUSIONS: Findings indicate emotion-related impulsivity may help explain transdiagnostic dimensions of psychopathology, such as the p factor.

First evidence on a general disease ("d") factor underlying psychopathology and physical illness in adolescents.

The coexistence of mental and physical health illnesses could be accounted for by an underlying general disease factor (termed d-factor), reflecting theoretical underpinnings based on possible genetic and pathophysiological overlapping mechanisms. This study evaluated whether the d-factor underlies mental and physical health illnesses in adolescents. A series of confirmatory factor analyses were conducted using data from 1120 adolescents. The proposed common underlying factor, we believe is the d-factor, was consistently present across different modeling approaches, including unidimensional, correlated-factor, and bifactor models. The best model fit was achieved with the bifactor model represented by mental, neurological, and psychical conditions tested. The first compelling evidence was provided supporting the existence of the transdiagnostic d-factor in youth, opening the door to innovative research of comorbid mental and physical health conditions.

Perinatal and neonatal factors and mental disorders in children and adolescents: looking for the contributions of the early environment to common and dissociable aspects of psychopathology.

High rates of co-occurrence of mental disorders have been hypothesized to represent a result of common susceptibility to overall psychopathology. The purpose of this study is to test the hypothesis that commonalities among psychiatric disorders might be partially driven by sharable perinatal and neonatal environmental factors for mental disorders. Participants were 6-14 years of age children and their parents. Primary caregivers provided data on perinatal and neonatal information assessed retrospectively (n = 2231). Psychiatric disorders diagnoses were assessed using the Development and Well Being Behavior Assessment (DAWBA). We used bifactor models to disentangle common from dissociable aspects of psychopathology. These models allow modeling psychiatric disorders as the result of a common domain of psychopathology (p-factor) and three dissociable domains (fear, distress, and externalizing symptoms). Associations were tested using linear and tobit regression models. The p-factor was associated with male sex, low socioeconomic status, gestational smoking, gestational drinking, low levels of maternal education and presence of mental disorder in the mother. Associations with specific factors also emerged suggesting some risk factors might also have some role for fear, distress and externalizing factors. Our study supports the hypothesis that overall susceptibility to psychopathology might be partially driven by sharable perinatal and neonatal factors.

Deriving the Transdiagnostic Scales From the Personality Assessment Inventory and SPECTRA: Indices of Psychopathology: A Demonstration.

Transdiagnostic models of psychopathology address many of the shortcomings common to categorical diagnostic systems. These empirically derived models conceptualize psychopathology as a few broad interrelated and hierarchically arranged dimensions, with an overarching general psychopathology dimension, the p-factor, at the apex. While transdiagnostic models are gaining prominence in mental health research, the lack of available tools has limited their clinical translation. The present study explored the potential of creating transdiagnostic scales from the joint factor structure of the Personality Assessment Inventory, Alternative Model of Personality Disorder trait scales (AMPD), and the clinical scales of the SPECTRA: Indices of Psychopathology (SPECTRA). Exploratory factor analysis in a clinical sample (n = 212) identified five factors corresponding to the Negative Affect/Internalizing, Detachment, Antagonism/Externalizing, Disinhibition/Externalizing, and Thought Disorder transdiagnostic dimensions. Goldberg's "Bass-Ackward" method supported a hierarchical structure. Five composite transdiagnostic scales were created by summing each factor's highest loading PAI and SPECTRA scales. A global psychopathology scale was created by summing the five composite scales. All the composite scales demonstrated adequate internal consistency. Correlations between the composite scales and the NEO Five-Factor Inventory-3 provide initial validity evidence for four composite and global scales. The composite thought disorder scale had no conceptually corresponding NEO domain. Clinical implications and study limitations are discussed.

Defining the p-factor: an empirical test of five leading theories.

BACKGROUND: Despite statistical evidence of a general factor of psychopathology (i.e., p-factor), there is little agreement about what the p-factor represents. Researchers have proposed five theories: dispositional negative emotionality (neuroticism), impulsive responsivity to emotions (impulsivity), thought dysfunction, low cognitive functioning, and impairment. These theories have primarily been inferred from patterns of loadings of diagnoses on p-factors with different sets of diagnoses included in different studies. Researchers who have directly examined these theories of p have examined a subset of the theories in any single sample, limiting the ability to compare the size of their associations with a p-factor. METHODS: In a sample of adults (N = 1833, Mage = 34.20, 54.4% female, 53.3% white) who completed diagnostic assessments, self-report measures, and cognitive tests, we evaluated statistical p-factor structures across modeling approaches and compared the strength of associations among the p-factor and indicators of each of these five theories. RESULTS: We found consistent evidence of the p-factor's unidimensionality across one-factor and bifactor models. The p-factor was most strongly and similarly associated with neuroticism (r = .88), impairment (r = .88), and impulsivity (r = .87), χ2(1)s < .15, ps > .70, and less strongly associated with thought dysfunction (r = .78), χ2(1)s > 3.92, ps < .05, and cognitive functioning (r = -.25), χ2(1)s > 189.56, ps < .01. CONCLUSIONS: We discuss a tripartite definition of p that involves the transaction of impulsive responses to frequent negative emotions leading to impairment that extends and synthesizes previous theories of psychopathology.

Do general and specific factors of preschool psychopathology predict preadolescent outcomes? A transdiagnostic hierarchical approach.

BACKGROUND: Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general ('p') and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence. METHODS: Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment. RESULTS: A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04-0.15) and functional impairment (ΔR2 = 0.01-0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06-0.15; functional impairment: ΔR2 = 0.05-0.12). CONCLUSIONS: Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

Interpretational issues with the bifactor model: a commentary on 'Defining the p-Factor: An Empirical Test of Five Leading Theories' by Southward, Cheavens, and Coccaro.

Southward, Cheavens, and Coccaro (2022, Psychological Medicine) conducted an ambitious investigation aimed at determining the nature of the general p factor of psychopathology by considering the correlation between the p factor and five candidate constructs. Generally, in this area of research, the bifactor model is preferred to the second order common factor model. In this commentary, we identify several interpretational issues concerning the bifactor model, which are based on a realistic psychometric view of latent variables. These issues may hamper the study of the nature of p factor model using the bifactor model.

The p factor of psychopathology and personality in middle childhood: genetic and gestational risk factors.

BACKGROUND: A joint, hierarchical structure of psychopathology and personality has been reported in adults but should also be investigated at earlier ages, as psychopathology often develops before adulthood. Here, we investigate the joint factor structure of psychopathology and personality in eight-year-old children, estimate factor heritability and explore external validity through associations with established developmental risk factors. METHODS: Phenotypic and biometric exploratory factor analyses with bifactor rotation on genetically informative data from the Norwegian Mother, Father, and Child Cohort (MoBa) study. The analytic sub-sample comprised 10 739 children (49% girls). Mothers reported their children's symptoms of depression (Short Moods and Feelings Questionnaire), anxiety (Screen for Anxiety Related Disorders), attention-deficit/hyperactivity disorder inattention and hyperactivity, oppositional-defiant disorder, conduct disorder (Parent/Teacher Rating Scale for Disruptive Behavior Disorders), and Big Five personality (short Hierarchical Personality Inventory for Children). Developmental risk factors (early gestational age and being small for gestational age) were collected from the Medical Birth Registry. RESULTS: Goodness-of-fit indices favored a p factor model with three residual latent factors interpreted as negative affectivity, positive affectivity, and antagonism, whereas psychometric indices favored a one-factor model. ADE solutions fitted best, and regression analyses indicated a negative association between gestational age and the p factor, for both the one- and four-factor solutions. CONCLUSION: Correlations between normative and pathological traits in middle childhood mostly reflect one heritable and psychometrically interpretable p factor, although optimal fit to data required less interpretable residual latent factors. The association between the p factor and low gestational age warrants further study of early developmental mechanisms.

Parent- and teacher-reported associations from adolescent bifactor models of psychopathology: an outcome-wide association study of 26 outcomes in mid-life.

BACKGROUND: Adolescent mental health problems have lasting impacts on health and social functioning later in life. Evidence to date mostly comes from studies of specific diagnostic categories/dimensions, but hierarchical models can elucidate associations with general as well as specific dimensions of psychopathology. We provide evidence on long-term outcomes of general and specific dimensions of adolescent psychopathology using both parent and teacher reports. METHODS: Parents and teachers from the Isle of Wight study completed Rutter behaviour scales when participants were 14-15 years old (n = 2,275), assessing conduct, emotional and hyperactivity problems. Metric-invariant bifactor models for parents and teachers were used to test domain-specific and domain-general associations with 26 self-reported psychosocial outcomes at mid-life (age 44-45 years, n = 1,423). Analyses examined the individual and joint contributions of parent and teacher reports of adolescent psychopathology. All analyses were adjusted for covariates (gender, IQ and family social class) and weighted to adjust for the probability of nonresponse. RESULTS: Parent- and teacher-reported general factors of psychopathology (GFP) were associated with 15 and 12 outcomes, respectively, across the socioeconomic, relationship, health and personality domains, along with an index of social exclusion. Nine outcomes were associated with both parent- and teacher-reported GFP, with no differences in the strength of the associations across reporters. Teacher-reported specific factors (conduct, emotional and hyperactivity) were associated with 21 outcomes, and parent-reported specific factors were associated with seven. Five outcomes were associated with the same specific factors from both reporters; only one showed reporter differences in the strength of the associations. CONCLUSIONS: These findings confirm the relevance of the GFP and the utility of teacher as well as parent reports of adolescent mental health in predicting psychosocial outcomes later in the life course.

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.

An integrative evolutionary framework for psychopathology.

The field of psychopathology is in a transformative phase, and is witnessing a renewed surge of interest in theoretical models of mental disorders. While many interesting proposals are competing for attention in the literature, they tend to focus narrowly on the proximate level of analysis and lack a broader understanding of biological function. In this paper, we present an integrative framework for mental disorders built on concepts from life history theory, and describe a taxonomy of mental disorders based on its principles, the fast-slow-defense model (FSD). The FSD integrates psychopathology with normative individual differences in personality and behavior, and allows researchers to draw principled distinctions between broad clusters of disorders, as well as identify functional subtypes within current diagnostic categories. Simulation work demonstrates that the model can explain the large-scale structure of comorbidity, including the apparent emergence of a general "p factor" of psychopathology. A life history approach also provides novel integrative insights into the role of environmental risk/protective factors and the developmental trajectories of various disorders.

The developmental interplay between the p-factor of psychopathology and the g-factor of intelligence from age 7 through 16 years.

Intelligence and mental health are the core pillars of individual adaptation, growth, and opportunity. Here, we charted across childhood and adolescence the developmental interplay between the p-factor of psychopathology, which captures the experience of symptoms across the spectrum of psychiatric disorders, and the g-factor of general intelligence that describes the ability to think, reason, and learn.Our preregistered analyses included 7,433 twin pairs from the Twins Early Development Study (TEDS), who were born 1994 to 1996 in England and Wales. At the ages 7, 9, 12, and 16 years, the twins completed two to four intelligence tests, and multi-informant measures (i.e., self-, parent- and teacher-rated) of psychopathology were collected.Independent of their cross-sectional correlations, p- and g-factors were linked by consistent, bidirectional, and negative cross-lagged paths across childhood and adolescence (from -.07 to -.13 with 95% CIs from -.03 to -.15). The cross-lagged paths from intelligence to psychopathology were largely due to genetic influences, but the paths from psychopathology to intelligence were driven by environmental factors, and increasingly so with age.Our findings suggest that intelligence and psychopathology are developmentally intertwined due to fluctuating etiological processes. Understanding the interplay of g- and p-factors is key for improving children's developmental outcomes.

Hoarding behavior and its association with mental health and functioning in a large youth sample.

Hoarding behavior is prevalent in children and adolescents, yet clinicians do not routinely inquire about it and youth may not spontaneously report it due to stigma. It is unknown whether hoarding behavior, over and above obsessive-compulsive symptoms (OCS), is associated with major clinical factors in a general youth population. This observational study included N = 7054 youth who were not seeking help for mental health problems (ages 11-21, 54% female) and completed a structured interview that included evaluation of hoarding behavior and OCS, as a part of the Philadelphia Neurodevelopmental Cohort between November 2009 and December 2011. We employed regression models with hoarding behavior and OCS (any/none) as independent variables, and continuous (linear regression) or binary (logistic regression) mental health measures as dependent variables. All models covaried for age, sex, race, and socioeconomic status. A total of 374 participants endorsed HB (5.3%), most of which reported additional OCS (n = 317). When accounting for OCS presence, hoarding behavior was associated with greater dimensional psychopathology burden (i.e., higher P-factor) (ß = 0.19, p < .001), and with poorer functioning (i.e., lower score on the child global assessment scale) (ß = - 0.07, p < .001). The results were consistent when modeling psychopathology using binary variables. The results remained significant in sensitivity analyses accounting for count of endorsed OCS and excluding participants who met criteria for obsessive-compulsive disorder (n = 210). These results suggest that hoarding behavior among youth is associated with poorer mental health and functioning, independent of OCS. Brief hoarding-behavior assessments in clinical settings may prove useful given hoarding behavior's stigma and detrimental health associations.

The relationship between general psychopathology in young people with family functioning and engagement with psychotherapy.

OBJECTIVE: to examine whether an underlying general psychopathology factor (p factor) existed in children and adolescents attending psychodynamic psychotherapy and whether this general psychopathology factor was associated with family functioning and engagement with psychotherapy. METHOD: Participants were 1976 children and adolescents, and their families, who sought psychodynamic psychotherapy from a community-based clinic in Southern Brazil. The Child Behavior Checklist and the Family Adaptability and Cohesion Evaluation Scales for assessing symptoms and family functioning were used, with treatment engagement data available through linked records. Confirmatory factor analytic methods examined psychopathology and regression models were constructed to examine associations. RESULTS: A general psychopathology factor and specific internalizing and externalizing factors were identified. Higher general psychopathology scores at assessment were associated with an increased likelihood of dropout and poorer attendance compared to completing treatment. Father's educational level, living with both parents, lack of family adaptability and cohesion, and maltreatment experience were related to increased p factor severity. CONCLUSION: General psychopathology severity seems to contribute to child and adolescent psychotherapy outcomes, increasing the risk of non-adherence and dropout. Family difficulties and traumatic experiences may increase p factor severity. Identifying general psychopathology routinely can be crucial for developing effective treatment plans.

Differentiated nomological networks of internalizing, externalizing, and the general factor of psychopathology ('p factor') in emerging adolescence in the ABCD study.

BACKGROUND: Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. METHODS: The sample consisted of 10 645 youth aged 9-10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance. RESULTS: p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. CONCLUSIONS: In this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

Longitudinal relations between impaired executive function and symptoms of psychiatric disorders in childhood.

BACKGROUND: Malfunctioning of executive functions correlates with psychopathology in children. However, the directionality, the extent to which the relation varies for various disorders, and whether prospective relations afford causal interpretations are not known. METHODS: A community sample of Norwegian children (n = 874) was studied biennially from the age of 6 to 14 years. Executive functions were assessed using the Behavior Rating Inventory of Executive Function Teacher-report and symptoms of psychopathology were assessed using the Preschool Age Psychiatric Assessment (age 6; parents) and Child and Adolescent Psychiatric Assessment (ages 8-14; children and parents). Prospective reciprocal relations were examined using a random intercept cross-lagged panel model that adjusts for all unobserved time-invariant confounders. RESULTS: Even when time-invariant confounders were accounted for, reduced executive functions predicted increased symptoms of depressive disorders, anxiety disorders, attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) 2 years later, even when previous changes in these symptoms were adjusted for. The level of prediction (B = .83, 95% CI [.37, 1.3]) was not different for different disorders or ages. Conversely, reduced executive functions were predicted by increased symptoms of all disorders (B = .01, 95% CI [.01, .02]). CONCLUSIONS: Reduced executive functioning may be involved in the etiology of depression, anxiety, ADHD, and ODD/CD to an equal extent. Moreover, increased depression, anxiety, ADHD, and ODD/CD may negatively impact executive functioning.

Infant temperament prospectively predicts general psychopathology in childhood.

Recent models of psychopathology suggest the presence of a general factor capturing the shared variance among all symptoms along with specific psychopathology factors (e.g., internalizing and externalizing). However, few studies have examined predictors that may serve as transdiagnostic risk factors for general psychopathology from early development. In the current study we examine, for the first time, whether observed and parent-reported infant temperament dimensions prospectively predict general psychopathology as well as specific psychopathology dimensions (e.g., internalizing and externalizing) across childhood. In a longitudinal cohort (N = 291), temperament dimensions were assessed at 4 months of age. Psychopathology symptoms were assessed at 7, 9, and 12 years of age. A bifactor model was used to estimate general, internalizing, and externalizing psychopathology factors. Across behavioral observations and parent-reports, higher motor activity in infancy significantly predicted greater general psychopathology in mid to late childhood. Moreover, low positive affect was predictive of the internalizing-specific factor. Other temperament dimensions were not related with any of the psychopathology factors after accounting for the general psychopathology factor. The results of this study suggest that infant motor activity may act as an early indicator of transdiagnostic risk. Our findings inform the etiology of general psychopathology and have implications for the early identification for children at risk for psychopathology.

Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology.

BACKGROUND: Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology ('p') factor. METHODS: Youth aged 8-16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. RESULTS: Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. CONCLUSIONS: Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.

The predictive capacity of psychiatric and psychological polygenic risk scores for distinguishing cases in a child and adolescent psychiatric sample from controls.

BACKGROUND: Psychiatric traits are heritable, highly comorbid and genetically correlated, suggesting that genetic effects that are shared across disorders are at play. The aim of the present study is to quantify the predictive capacity of common genetic variation of a variety of traits, as captured by their PRS, to predict case-control status in a child and adolescent psychiatric sample including controls to reveal which traits contribute to the shared genetic risk across disorders. METHOD: Polygenic risk scores (PRS) of 14 traits were used as predictor phenotypes to predict case-control status in a clinical sample. Clinical cases (N = 1,402), age 1-21, diagnostic categories: Autism spectrum disorders (N = 492), Attention-deficit/ hyperactivity disorders (N = 471), Anxiety (N = 293), disruptive behaviors (N = 101), eating disorders (N = 97), OCD (N = 43), Tic disorder (N = 50), Disorder of infancy, childhood or adolescence NOS (N = 65), depression (N = 64), motor, learning and communication disorders (N = 59), Anorexia Nervosa (N = 48), somatoform disorders (N = 47), Trauma/stress (N = 39) and controls (N = 1,448, age 17-84) of European ancestry. First, these 14 PRS were tested in univariate regression analyses. The traits that significantly predicted case-control status were included in a multivariable regression model to investigate the gain in explained variance when leveraging the genetic effects of multiple traits simultaneously. RESULTS: In the univariate analyses, we observed significant associations between clinical status and the PRS of educational attainment (EA), smoking initiation (SI), intelligence, neuroticism, alcohol dependence, ADHD, major depression and anti-social behavior. EA (p-value: 3.53E-20, explained variance: 3.99%, OR: 0.66), and SI (p-value: 4.77E-10, explained variance: 1.91%, OR: 1.33) were the most predictive traits. In the multivariable analysis with these eight significant traits, EA and SI, remained significant predictors. The explained variance of the PRS in the model with these eight traits combined was 5.9%. CONCLUSION: Our study provides more insights into the genetic signal that is shared between childhood and adolescent psychiatric disorders. As such, our findings might guide future studies on psychiatric comorbidity and offer insights into shared etiology between psychiatric disorders. The increase in explained variance when leveraging the genetic signal of different predictor traits supports a multivariable approach to optimize precision accuracy for general psychopathology.