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Nat Commun. 2018 Aug 1;9(1):3003. doi: 10.1038/s41467-018-05317-y.

Linked dimensions of psychopathology and connectivity in functional brain networks.

Author information

1
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
2
Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, 19104, USA.
3
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.
4
Department of Computer Science and Engineering, University of Electronic Science and Technology, Chengdu, Sichuan, 611731, China.
5
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
6
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
7
Department of Electrical and Systems Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.
8
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. sattertt@pennmedicine.upenn.edu.

Abstract

Neurobiological abnormalities associated with psychiatric disorders do not map well to existing diagnostic categories. High co-morbidity suggests dimensional circuit-level abnormalities that cross diagnoses. Here we seek to identify brain-based dimensions of psychopathology using sparse canonical correlation analysis in a sample of 663 youths. This analysis reveals correlated patterns of functional connectivity and psychiatric symptoms. We find that four dimensions of psychopathology - mood, psychosis, fear, and externalizing behavior - are associated (r = 0.68-0.71) with distinct patterns of connectivity. Loss of network segregation between the default mode network and executive networks emerges as a common feature across all dimensions. Connectivity linked to mood and psychosis becomes more prominent with development, and sex differences are present for connectivity related to mood and fear. Critically, findings largely replicate in an independent dataset (n = 336). These results delineate connectivity-guided dimensions of psychopathology that cross clinical diagnostic categories, which could serve as a foundation for developing network-based biomarkers in psychiatry.

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