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. 2015 Dec;56(12):1356-1369.
doi: 10.1111/jcpp.12416. Epub 2015 Apr 8.

The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative

Monica E Calkins  1 , Kathleen R Merikangas  2 , Tyler M Moore  1 , Marcy Burstein  2 , Meckenzie A Behr  3 , Theodore D Satterthwaite  1 , Kosha Ruparel  1 , Daniel H Wolf  1 , David R Roalf  1 , Frank D Mentch  3 , Haijun Qiu  3 , Rosetta Chiavacci  3 , John J Connolly  3 , Patrick M A Sleiman  4 , Ruben C Gur  1 , Hakon Hakonarson #  3 , Raquel E Gur #  1
Affiliations

The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative

Monica E Calkins et al. J Child Psychol Psychiatry. 2015 Dec.

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.

Keywords: Community cohort; adolescents; anxiety; behavior; children; comorbidity; genomics; mood; neurocognition; neuroimaging; psychopathology; psychosis; public domain; structure; young adults.

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Figures

Figure 1
Figure 1
Recruitment flow of the Philadelphia Neurodevelopmental Cohort. Among ineligible youths (n=31,132), approximately 31% had serious medical conditions precluding participation in the study procedures (severe developmental delay, significant hearing loss, limited mobility), 44% were outside the study age range or deceased, and 36% declined to be re-contacted for future studies.
Figure 2
Figure 2
a. Number of clinical assessments by date of assessment. b. Date of clinical assessment by proband age.
Figure 3
Figure 3
a. Confirmatory bifactor analysis of the GOASSESS with sex as a covariate (n=9,361). PTSD=Post-traumatic Stress; MDE=Major Depressive Episode; Eating= Anorexia/Bulimia; GAD=Generalized Anxiety; Separation=Separation Anxiety; Panic=Panic; OCD=Obsessive Compulsive; ADHD=Attention Deficit/Hyperactivity; ODD=Oppositional Defiant. b. Exploratory Bifactor (Schmid-Leiman) Rotation of the Psychosis Spectrum Screening Tools in Adolescents and Young Adults (n=6,963). See Table 2 for items/tools associated with each variable.
See this image and copyright information in PMC

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