Biology subjects

Kotov, R.

Publications and source records attributed to Kotov, R..

3 recordsLinked to original sources

bioRxiv2020

Associations Between Resting State Functional Connectivity and a Hierarchical Dimensional Structure of Psychopathology in Middle Childhood

BackgroundPrevious research from the Adolescent Brain Cognitive Development (ABCD) study delineated and validated a hierarchical 5-factor structure with a general psychopathology ( p) factor at the apex and five specific factors (internalizing, somatoform, detachment, neurodevelopmental, externalizing) using parent-reported child symptoms. The current study is the first examining associations between dimensions from a hierarchical structure and resting state functional connectivity (RSFC) networks. MethodsUsing 9-11-year-old children from the ABCD baseline sample, we compared the variance explained by each hierarchy level (p-factor, 2-factor, 3-factor, 4-factor, and 5-factor models) in RSFC. Analyses were first conducted in a discovery dataset (n=3790) with significant associations examined in a replication dataset (n=3791). ResultsThe current study found associations between p-factor and lower connectivity within default mode network (DMN), although stronger effects emerged for the neurodevelopmental factor. Neurodevelopmental impairments were related to variation in RSFC networks associated with attention to internal states and external stimuli. These networks included within DMN, DMN with cingulo-opercular (CON) and Other (Unassigned) networks, CON with ventral attention and Other network, and dorsal attention with Other network. Results held when accounting for parental psychopathology. ConclusionThe hierarchical structure of psychopathology showed replicable links to RSFC alterations in middle childhood. The p-factor had minimal association with altered connectivity, while the specific neurodevelopmental dimension showed robust associations with multiple RSFC impairments. Results show the utility of examining associations between intrinsic brain architecture and specific dimensions of psychopathology, revealing associations specifically with neurodevelopmental impairments.

neuroscience↗

bioRxiv2019

Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders

Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnostics and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms ({beta} = 0.21), lower GAF ({beta} = -0.28), and worse cognition ({beta} = -0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a powerful tool for diagnosis and treatment planning.

genetics↗

bioRxiv2019

Delineating and validating higher-order dimensions of psychopathology in the Adolescent Brain Cognitive Development (ABCD) study

Hierarchical dimensional systems of psychopathology promise more informative descriptions for understanding risk and predicting outcome than traditional diagnostic systems, but it is unclear how many major dimensions they should include. We delineated the hierarchy of childhood and adult psychopathology and validated it against clinically-relevant measures. Participants were 4,524 9- and 10-year-old children and their parents from the Adolescent Brain Cognitive Development (ABCD) study. Factor analyses on items from the Child Behavior Checklist and Adult Self-Report characterized a dimensional hierarchy. We examined the familial aggregation of the psychopathology dimensions, and the ability of different factor solutions to account for risks factors, social, educational and cognitive functioning, and physical and mental health service utilization. A hierarchical structure with a general psychopathology ( p) factor at the apex and five specific factors (internalizing, somatoform, detachment, neurodevelopmental, and externalizing) emerged in children. Adult factors were similar, but externalizing behaviors separated into disinhibited and antagonistic factors. Child and parent p-factors correlated highly (r=.61, P<.001), and smaller but significant correlations emerged for convergent dimensions between parents and children after controlling for p-factors (r=.10-20, P<.001). A model with childhood p-factor alone explained mental health service utilization (R2=.13, P<.001), but up to five dimensions provided incremental validity to account for developmental risk and current functioning (R2=.03-.20, P<.001). In this first investigation comprehensively mapping the psychopathology hierarchy in children and adults, we delineated a hierarchy of higher-order dimensions associated with a range of clinically-relevant validators. These findings hold important implications for psychiatric nosology and future research in this sample.

epidemiology↗