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Updated: Apr 15, 2026
Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
Published on: March 2, 2018
The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative
Monica E Calkins1, Kathleen R Merikangas2, Tyler M Moore1
1University of Pennsylvania, Department of Psychiatry, Neuropsychiatry Section, Perelman School of Medicine, PA, United States.
Insights
The Philadelphia Neurodevelopmental Cohort (PNC) study found that psychopathology in youths can be categorized into general and specific factors, aiding research into mental disorders. This data is valuable for understanding gene-brain-behavior links in youth mental health.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
- Developmental Psychology
Background:
- Understanding neurodevelopmental trajectories of mental disorders requires an integrative, multidisciplinary approach.
- The Philadelphia Neurodevelopmental Cohort (PNC) was established to characterize clinical and neurobehavioral phenotypes in genotyped youths.
- PNC data is now publicly available via the NIMH Database of Genotypes and Phenotypes (dbGaP).
Purpose of the Study:
- To provide an overview of PNC recruitment and clinical assessment methods for the scientific community.
- To evaluate the structure and criterion validity of the assessment tools used in the PNC.
- To enable informed use and interpretation of the PNC resource.
Main Methods:
- Recruited 9,498 youths (aged 8-21) from a larger pool previously genotyped at The Children's Hospital of Philadelphia.
- Developed and administered a comprehensive computerized tool for structured evaluation of psychopathology domains (GOASSESS).
- Utilized factor analysis to evaluate the structure of the GOASSESS tool.
Main Results:
- Factor analysis revealed a strong general psychopathology factor and specific factors: 'anxious-misery', 'fear', and 'behavior'.
- The 'behavior' factor showed a negative correlation with neurocognitive performance, especially executive functions.
- Sex differences were observed, with females higher on 'anxious-misery' and lower on 'behavior' factors; psychosis spectrum symptoms also showed distinct factor structures.
Conclusions:
- The PNC assessment yielded psychopathology data with strong factorial validity in a diverse cohort of genotyped youths.
- PNC factor scores are suitable for dimensional integration with other data modalities like neuroimaging and genomics.
- PNC resources can advance the understanding of gene-cognition-brain-behavior relationships in the neurodevelopment of common mental disorders.
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.
