Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.

The sample (N = 9350; age 8–21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology (‘p’) factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors.

The final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively).

By modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.

Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamlines evaluation of neurocognitive functioning. Our group translated and culturally adapted the PennCNB for use among children and adolescents in this high-burden, low-resource setting. The current study examined the construct validity and sensitivity to HIV infection and exposure of the culturally adapted PennCNB among a cohort of HIV-affected children and adolescents in Gaborone, Botswana.

628 school-aged children aged 7-17 years (n=223 children living with HIV [HIV+]; n=204 HIV exposed, uninfected [HEU]; and 201 HIV unexposed, uninfected [HUU]) completed the PennCNB. Participants were recruited from a clinic specializing in the care and treatment of HIV+ children and adolescents in Gaborone, Botswana, as well as from local schools. Confirmatory factor analyses were performed on efficiency measures for 13 PennCNB tests. Multiple regressions examined associations between HIV and neurocognitive functioning while controlling for age and sex. Multivariate normative comparisons were used to examine rates of overall cognitive impairment by comparing individual profiles of test scores to the multivariate distribution of test scores using age-normed data from the HUU group.

Confirmatory factor analysis supported four hypothesized neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. As expected, there were main effects of age on cognitive performance across all domains (ps < .001), and there were small sex differences, with females performing better in executive functioning and males performing better on visuospatial processing. Children and adolescents living with HIV performed significantly worse than HUU across all domains (ps < .001), with the largest effect sizes on measures of abstraction, working memory, and processing speed. HEU also performed worse than HUU across several domains, with smaller effect sizes. Multivariate normative comparisons indicated that 27% of the HIV+ group evidenced global neurocognitive impairment.

Overall, results support the validity of a neurocognitive battery adapted for use in Botswana, a non-Western, resource-limited setting. Results indicated that the adapted battery applied to children and adolescents with limited computer familiarity had a similar factor structure as in Western settings, indicating that the PennCNB appeared to assess the hypothesized neurocognitive domains. Hypothesized associations with age and sex supported the battery’s construct validity. Moreover, the battery appears to be sensitive to cognitive impairments associated with perinatally-acquired HIV and in utero HIV-related exposures, as it discriminated between the HUU, HIV+, and HEU groups. Differences were found in specific domains and in detection of overall impairment, including approximately one quarter of children and adolescents living with HIV in this cohort evidencing global neurocognitive impairment. Together, these results provide evidence that the PennCNB could serve as a useful tool for the assessment of neurocognitive functioning in school-aged children and adolescents from Botswana and, potentially, other resource-limited settings.

Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome.

157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−).

We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change.

Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).

We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).

Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.

These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.

Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.

Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.

Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.

Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.

Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples.

We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting ‘psychosis risk’ enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines.

Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70.

Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS.

Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.

To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.

Participants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.

Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.

Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.

R.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.

Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.

The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.

Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.

Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.