Publications by authors named "Ruben Gur"

Background And Hypothesis: Improvements in screening tools for early subthreshold psychosis symptoms are needed to facilitate early identification and intervention efforts, especially given the challenges of rapidly differentiating age-appropriate experiences from potential early signs of emerging psychosis. Tools can be lengthy and time-consuming, impacting their utility and accessibility across clinical settings, and age-normed data are limited. To address this gap, we sought to develop and validate a brief, empirically derived, age-normed, subthreshold psychosis screening tool, for public use.

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The 22q11.2 Deletion Syndrome (22q11.2DS) is a multisystem genetic disorder with prominent sleep disturbances, neuropsychiatric conditions and neurocognitive challenges.

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Some but not other studies on oxytocin for schizophrenia, particularly those using a higher dose, indicate that oxytocin improves negative symptoms of schizophrenia. We performed an add-on randomized controlled trial to examine the effect of high-dose oxytocin, social skills training, and their combination in the treatment of negative symptoms and social dysfunction in schizophrenia. Fifty-one subjects with schizophrenia were randomized, employing a two-by-two design: intranasal oxytocin (24 IU X3/day) or placebo, and social skills training or supportive psychotherapy, for 3 weeks.

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Article Synopsis
  • Schizophrenia (SCZ) shows differences in brain structure and symptoms between men and women, suggesting distinct neurobiological factors linked to sex.
  • The study analyzed MRI data from nearly 6,000 participants to explore the effects of sex and diagnosis on the shape of deep brain regions in individuals with SCZ compared to healthy controls.
  • Results indicated that women with SCZ had more pronounced shape abnormalities than men, but there were no significant interactions between diagnosis and sex, highlighting the need for further exploration of sex-related differences in schizophrenia's neurobiology.
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Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects one million people in the United States. Up to 50% of people with MS experience depression, yet the mechanisms of depression in MS remain under-investigated. Studies of medically healthy participants with depression have described associations between white matter variability and depressive symptoms, but frequently exclude participants with medical comorbidities and thus cannot be extrapolated to people with intracranial diseases.

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Deficiencies in response inhibition are associated with numerous mental health conditions, warranting innovative treatments. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates cortical excitability and has shown promise in improving response inhibition. However, tDCS effects on response inhibition often yield contradictory findings.

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In the brain, functional connections form a network whose topological organization can be described by graph-theoretic network diagnostics. These include characterizations of the community structure, such as modularity and participation coefficient, which have been shown to change over the course of childhood and adolescence. To investigate if such changes in the functional network are associated with changes in cognitive performance during development, network studies often rely on an arbitrary choice of preprocessing parameters, in particular the proportional threshold of network edges.

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Network control theory (NCT) is a simple and powerful tool for studying how network topology informs and constrains the dynamics of a system. Compared to other structure-function coupling approaches, the strength of NCT lies in its capacity to predict the patterns of external control signals that may alter the dynamics of a system in a desired way. An interesting development for NCT in the neuroscience field is its application to study behavior and mental health symptoms.

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Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders.

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Article Synopsis
  • The article discusses how the relationship between brain structure and function changes as individuals develop, potentially influencing the risk of neuropsychiatric disorders.
  • It highlights the need for better methods to examine individual differences in this structure-function relationship and introduces a new method called CIDeR aimed at reducing false positives in data analysis.
  • The authors demonstrate CIDeR's effectiveness through comparisons with existing methods and provide applications to brain development research using actual data from the Philadelphia Neurodevelopmental Cohort.
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Objective: Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC).

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Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model.

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Background: Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders.

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Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence. The brain's capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth.

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Functional networks often guide our interpretation of spatial maps of brain-phenotype associations. However, methods for assessing enrichment of associations within networks of interest have varied in terms of both scientific rigor and underlying assumptions. While some approaches have relied on subjective interpretations, others have made unrealistic assumptions about spatial properties of imaging data, leading to inflated false positive rates.

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Accumulating evidence supports the presence of a general psychopathology dimension, the p factor ('p'). Despite growing interest in the p factor, questions remain about how p is assessed. Although multi-informant assessment of psychopathology is commonplace in clinical research and practice with children and adolescents, almost no research has taken a multi-informant approach to studying youth p or has examined the degree of concordance between parent and youth reports.

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Background: 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.

Method: The sample ( = 9350; age 8-21 years) was drawn from the Philadelphia Neurodevelopmental Cohort.

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A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data.

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Social isolation has been linked to a range of psychiatric issues, but the behavioral component that drives it is not well understood. Here, a genome-wide associations study (GWAS) was carried out to identify genetic variants that contribute specifically to social isolation behavior (SIB) in up to 449,609 participants from the UK Biobank. 17 loci were identified at genome-wide significance, contributing to a 4% SNP-based heritability estimate.

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Human cortical maturation has been posited to be organized along the sensorimotor-association 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 sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126).

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A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here we non-invasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically-plausible circuit model to resting-state functional MRI (fMRI) data.

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Large-scale studies and burdened clinical settings require precise, efficient measures that assess multiple domains of psychopathology. Computerized adaptive tests (CATs) can reduce administration time without compromising data quality. We examined feasibility and validity of an adaptive psychopathology measure, GOASSESS, in a clinical community-based sample (N = 315; ages 18-35) comprising three groups: healthy controls, psychosis, mood/anxiety disorders.

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Schizophrenia is characterized by the misattribution of emotional significance to neutral faces, accompanied by overactivations of the limbic system. To understand the disorder's genetic and environmental contributors, investigating healthy first-degree relatives is crucial. However, inconsistent findings exist regarding their ability to recognize neutral faces, with limited research exploring the cerebral correlates of neutral face processing in this population.

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This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community.

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Background: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas.

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