Raquel E. Gur

Background Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in‐person assessment can be unavailable or burdensome. The current study compares in‐person and remote assessments of the Penn computerised neurocognitive battery (CNB). Methods Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in‐person at a laboratory (n = 222) or remotely (n = 162). Results Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. Conclusions These findings suggest that the CNB can be used in remote settings to …

BackgroundThe Penn Computerized Neurocognitive Battery is an efficient tool for assessing brain-behavior domains, and its efficiency was augmented via computerized adaptive testing (CAT). This battery requires validation in a separate sample to establish psychometric properties.MethodsIn a mixed community/clinical sample of N = 307 18-to-35-year-olds, we tested the relationships of the CAT tests with the full-form tests. We compared discriminability among recruitment groups (psychosis, mood, control) and examined how their scores relate to demographics. CAT-Full relationships were evaluated based on a minimum inter-test correlation of 0.70 or an inter-test correlation within at least 0.10 of the full-form correlation with a previous administration of the full battery. Differences in criterion relationships were tested via mixed models.ResultsMost tests (15/17) met the minimum criteria for replacing the full-form …

BackgroundIn this study, we explored the relationship between genetics, trauma exposure, and social environment in a community cohort of youth. Since most methods that test gene-environment interaction (GxE) assume independence of genetic and environmental factors we aimed to investigate whether genetic factors play a role in the association between trauma and psychopathology.MethodsOur sample consisted of 5168 European ancestry (EA) and 3170 African ancestry (AA) 8–21-year-old participants (51.7% female). Trauma exposure was assessed through structured psychopathology evaluations, and social environment was determined using census and crime data. Polygenic Scores (PGS) for height, major depression (MDD), schizophrenia, post-traumatic stress disorder, and suicide attempts were calculated in both ancestry groups, whereas intelligence quotient (IQ), attention deficit hyperactivity …

Human cortical maturation has been posited to be organized along the sensorimotor-association (S-A) axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the S-A axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3,355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1,207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1,126). In each dataset, the development of functional connectivity systematically varied along the S-A axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These robust and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1‐weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source‐based morphometry (SBM) pipeline (SS‐Detect) to generate structural brain patterns (SBPs) that capture co‐varying GMV. We investigated the impact of the 22q11.2 deletion …

With new data about different aspects of schizophrenia being continually generated, it becomes necessary to periodically revisit exactly what we know. Along with a need to review what we currently know about schizophrenia, there is an equal imperative to evaluate the construct itself. With these objectives, we undertook an iterative, multi-phase process involving fifty international experts in the field, with each step building on learnings from the prior one. This review assembles currently established findings about schizophrenia (construct, etiology, pathophysiology, clinical expression, treatment) and posits what they reveal about its nature. Schizophrenia is a heritable, complex, multi-dimensional syndrome with varying degrees of psychotic, negative, cognitive, mood, and motor manifestations. The illness exhibits a remitting and relapsing course, with varying degrees of recovery among affected individuals with most …

BackgroundFamily history of psychopathology (FH) can influence adolescent mental health through both environment and genetics. Simultaneously, traumatic events are widely recognized as conveying significant risk for psychopathology. Interrogation of the potential indirect pathway of FH via trauma on psychopathology is warranted, particularly when viewed as a potentially actionable point of intervention.MethodsThe Philadelphia Neurodevelopmental Cohort is a deeply-phenotyped collection of 9,498 youth who were recruited through nonpsychiatric pediatric clinics. We tested associations of FH (count [0 to 4] of categories: psychosis, mood, suicide attempt, and substance use), youth trauma exposure, geocoded structural neighborhood environment, and genomic factor of polygenic scores for psychopathologies (depression, PTSD, schizophrenia, bipolar, cross-disorder) with overall adolescent …

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3–90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The …