title: The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative.
abstract: BACKGROUND
  An integrative multidisciplinary approach is required to elucidate the multiple factors that shape neurodevelopmental trajectories of mental disorders. The Philadelphia Neurodevelopmental Cohort (PNC), funded by the National Institute of Mental Health Grand Opportunity (GO) mechanism of the American Recovery and Reinvestment Act, was designed to characterize clinical and neurobehavioral phenotypes of genotyped youths. Data generated, which are recently available through the NIMH Database of Genotypes and Phenotypes (dbGaP), have garnered considerable interest. We provide an overview of PNC recruitment and clinical assessment methods to allow informed use and interpretation of the PNC resource by the scientific community. We also evaluate the structure of the assessment tools and their criterion validity.
  
  
  METHODS
  Participants were recruited from a large pool of youths (n = 13,958) previously identified and genotyped at The Children's Hospital of Philadelphia. A comprehensive computerized tool for structured evaluation of psychopathology domains (GOASSESS) was constructed. We administered GOASSESS to all participants and used factor analysis to evaluate its structure.
  
  
  RESULTS
  A total of 9,498 youths (aged 8-21; mean age = 14.2; European American = 55.8%; African American = 32.9%; Other = 11.4%) were enrolled. Factor analysis revealed a strong general psychopathology factor, and specific 'anxious-misery', 'fear', and 'behavior' factors. The 'behavior' factor had a small negative correlation (-0.21) with overall accuracy of neurocognitive performance, particularly in tests of executive and complex reasoning. Being female had a high association with the 'anxious-misery' and low association with the 'behavior' factors. The psychosis spectrum was also best characterized by a general factor and three specific factors: ideas about 'special abilities/persecution,' 'unusual thoughts/perceptions', and 'negative/disorganized' symptoms.
  
  
  CONCLUSIONS
  The PNC assessment mechanism yielded psychopathology data with strong factorial validity in a large diverse community cohort of genotyped youths. Factor scores should be useful for dimensional integration with other modalities (neuroimaging, genomics). Thus, PNC public domain resources can advance understanding of complex inter-relationships among genes, cognition, brain, and behavior involved in neurodevelopment of common mental disorders.
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Monica E
authors: ME
authors: Calkins
authors: National Institute of Mental Health, Genetic Epidemiology Research Branch, Intramural Research Program, Bethesda, MD, United States.
authors: Kathleen R
authors: KR
authors: Merikangas
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Tyler M
authors: TM
authors: Moore
authors: National Institute of Mental Health, Genetic Epidemiology Research Branch, Intramural Research Program, Bethesda, MD, United States.
authors: Marcy
authors: M
authors: Burstein
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: Meckenzie A
authors: MA
authors: Behr
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Theodore D
authors: TD
authors: Satterthwaite
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Kosha
authors: K
authors: Ruparel
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Daniel H
authors: DH
authors: Wolf
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: David R
authors: DR
authors: Roalf
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: Frank D
authors: FD
authors: Mentch
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: Haijun
authors: H
authors: Qiu
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: Rosetta
authors: R
authors: Chiavacci
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: John J
authors: JJ
authors: Connolly
authors: Department of Pediatrics,The Perelman School of Medicine, University of Pennsylvania, PA, United States.
authors: Patrick M A
authors: PMA
authors: Sleiman
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Ruben C
authors: RC
authors: Gur
authors: Center for Applied Genomics at The Children's Hospital of Philadelphia, PA, United States.
authors: Hakon
authors: H
authors: Hakonarson
authors: University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
authors: Raquel E
authors: RE
authors: Gur
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D003299:Cooperative Behavior; D016208:Databases, Factual; D030541:Databases, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D065886:Neurodevelopmental Disorders / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D015143:Philadelphia; D055815:Young Adult
keywords: Community cohort; adolescents; anxiety; behavior; children; comorbidity; genomics; mood; neurocognition; neuroimaging; psychopathology; psychosis; public domain; structure; young adults