Abstract

Conventional research methodologies and data analytic approaches in psychiatric research are unable to reliably infer causal relations without experimental designs, or to make inferences about the functional properties of the complex systems in which psychiatric disorders are embedded. This article describes a series of studies to validate a novel hybrid computational approach–the Complex Systems-Causal Network (CS-CN) method–designed to integrate causal discovery within a complex systems framework for psychiatric research. The CS-CN method was first applied to an existing dataset on psychopathology in 163 children hospitalized with injuries (validation study). Next, it was applied to a much larger dataset of traumatized children (replication study). Finally, the CS-CN method was applied in a controlled experiment using a ‘gold standard’ dataset for causal discovery and compared with other methods for accurately detecting causal variables (resimulation controlled experiment). The CS-CN method successfully detected a causal network of 111 variables and 167 bivariate relations in the initial validation study. This causal network had well-defined adaptive properties and a set of variables was found that disproportionally contributed to these properties. Modeling the removal of these variables resulted in significant loss of adaptive properties. The CS-CN method was successfully applied in the replication study and performed better than traditional statistical methods, and similarly to state-of-the-art causal discovery algorithms in the causal detection experiment. The CS-CN method was validated, replicated, and yielded both novel and previously validated findings related to risk factors and potential treatments of psychiatric disorders. The novel approach yields both fine-grain (micro) and high-level (macro) insights and thus represents a promising approach for complex systems-oriented research in psychiatry.

Highlights

  • There is an astonishing array of advances in areas such as genomics, proteomics, and functional brain imaging that can provide detailed information about the nature of psychiatric disorders

  • An adaptive network is highly robust to challenge by random node removal. This process of ‘error tolerance vs. attack vulnerability’ is thought to be an important quality of a Complex Adaptive System (CAS) [11,12,13]. The modeling of these forms of challenge offers two advantages: 1. The results will reveal whether the network ‘behaves’ consistently with other Complex Adaptive Systems (CAS) to challenge, supporting a conclusion that our method has identified a CAS related to a psychiatric disorder of interest, and 2

  • We developed a computational approach that enables and integrates causal and systems level inference in a unified analysis for psychiatric research

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Summary

Introduction

There is an astonishing array of advances in areas such as genomics, proteomics, and functional brain imaging that can provide detailed information about the nature of psychiatric disorders. The capacity to integrate this knowledge with information related to phenotypic expression in the form of cognition, emotion, and behavior, and information related to developmental and environmental risk, opens new frontiers for understanding the nature of psychiatric disorders These opportunities will not be harvested, without the development and evaluation of new computational methods and tools needed for integrating the diversity of modalities of information (e.g. genes, proteins, brain circuitry, developmental, social, behavioral) into unified analyses. Yield knowledge of the behavior of the complex system (e.g. psychiatric disorder) itself: This knowledge will need to develop from methods that can provide meaningful information about the behavior of the system as a whole, including how the system and its components emerge and are sustained over time Such methods will need a successful approach for integrating diverse forms of information. Research has been conducted on several of these components such as brain, gene, and phenotypic networks [1,2,3,4,5,6,7,8,9,10], the development and employment of methods to handle the integration of diverse forms of information (e.g. molecular, brain circuitry, developmental, social, behavioral) in a consistent, and meaningful, fashion will be very important

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