The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative.

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TitleThe Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative.
Publication TypeJournal Article
Year of Publication2015
AuthorsCalkins, ME, Merikangas, KR, Moore, TM, Burstein, M, Behr, MA, Satterthwaite, TD, Ruparel, K, Wolf, DH, Roalf, DR, Mentch, FD, Qiu, H, Chiavacci, R, Connolly, JJ, Sleiman, PMA, Gur, RC, Hakonarson, H, Gur, RE
JournalJ Child Psychol Psychiatry
Volume56
Issue12
Pagination1356-1369
Date Published2015 Dec
ISSN1469-7610
KeywordsAdolescent, Adult, Child, Cohort Studies, Cooperative Behavior, Databases, Factual, Databases, Genetic, Female, Genotype, Humans, Male, Neurodevelopmental Disorders, Phenotype, Philadelphia, Young Adult
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.

DOI10.1111/jcpp.12416
Alternate JournalJ Child Psychol Psychiatry
PubMed ID25858255
PubMed Central IDPMC4598260
Grant ListK08MH079364 / MH / NIMH NIH HHS / United States
MH089924 / MH / NIMH NIH HHS / United States
K23 MH098130 / MH / NIMH NIH HHS / United States
K08 MH079364 / MH / NIMH NIH HHS / United States
RC2 MH089924 / MH / NIMH NIH HHS / United States
K23MH098130 / MH / NIMH NIH HHS / United States
MH089983 / MH / NIMH NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States
RC2 MH089983 / MH / NIMH NIH HHS / United States
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