Selectively predicting the onset of ADHD, oppositional defiant disorder, and conduct disorder in early adolescence with high accuracy.

Introduction: The externalizing disorders of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are common in adolescence and are strong predictors of adult psychopathology. While treatable, substantial diagnostic overlap complicates intervention planning. Understanding which factors predict the onset of each disorder and disambiguating their different predictors is of substantial translational interest. Materials and methods: We analyzed 5,777 multimodal candidate predictors from children aged 9-10 years and their parents in the ABCD cohort to predict the future onset of ADHD, ODD, and CD at 2-year follow-up. We used deep learning optimized with an innovative AI algorithm to jointly optimize model training, perform automated feature selection, and construct individual-level predictions of illness onset and all prevailing cases at 11-12 years and examined relative predictive performance when candidate predictors were restricted to only neural metrics. Results: Multimodal models achieved ~86-97% accuracy, 0.919-0.996 AUROC, and ~82-97% precision and recall in testing in held-out, unseen data. In neural-only models, predictive performance dropped substantially but nonetheless achieved accuracy and AUROC of ~80%. Parent aggressive and externalizing traits uniquely differentiated the onset of ODD, while structural MRI metrics in the limbic system were specific to CD. Psychosocial measures of sleep disorders, parent mental health and behavioral traits, and school performance proved valuable across all disorders. In neural-only models, structural and functional MRI metrics in subcortical regions and cortical-subcortical connectivity were emphasized. Overall, we identified a strong correlation between accuracy and final predictor importance. Conclusion: Deep learning optimized with AI can generate highly accurate individual-level predictions of the onset of early adolescent externalizing disorders using multimodal features. While externalizing disorders are frequently co-morbid in adolescents, certain predictors were specific to the onset of ODD or CD vs. ADHD. To our knowledge, this is the first machine learning study to predict the onset of all three major adolescent externalizing disorders with the same design and participant cohort to enable direct comparisons, analyze >200 multimodal features, and include many types of neuroimaging metrics. Future study to test our observations in external validation data will help further test the generalizability of these findings.

Predicting new onset thought disorder in early adolescence with optimized deep learning implicates environmental-putamen interactions.

Background: Thought disorder (TD) is a sensitive and specific marker of risk for schizophrenia onset. Specifying factors that predict TD onset in adolescence is important to early identification of youth at risk. However, there is a paucity of studies prospectively predicting TD onset in unstratified youth populations. Study Design: We used deep learning optimized with artificial intelligence (AI) to analyze 5,777 multimodal features obtained at 9-10 years from youth and their parents in the ABCD study, including 5,014 neural metrics, to prospectively predict new onset TD cases at 11-12 years. The design was replicated for all prevailing TD cases at 11-12 years. Study Results: Optimizing performance with AI, we were able to achieve 92% accuracy and F1 and 0.96 AUROC in prospectively predicting the onset of TD in early adolescence. Structural differences in the left putamen, sleep disturbances and the level of parental externalizing behaviors were specific predictors of new onset TD at 11-12 yrs, interacting with low youth prosociality, the total parental behavioral problems and parent-child conflict and whether the youth had already come to clinical attention. More important predictors showed greater inter-individual variability. Conclusions: This study provides robust person-level, multivariable signatures of early adolescent TD which suggest that structural differences in the left putamen in late childhood are a candidate biomarker that interacts with psychosocial stressors to increase risk for TD onset. Our work also suggests that interventions to promote improved sleep and lessen parent-child psychosocial stressors are worthy of further exploration to modulate risk for TD onset.

Predicting individual cases of major adolescent psychiatric conditions with artificial intelligence.

Three-quarters of lifetime mental illness occurs by the age of 24, but relatively little is known about how to robustly identify youth at risk to target intervention efforts known to improve outcomes. Barriers to knowledge have included obtaining robust predictions while simultaneously analyzing large numbers of different types of candidate predictors. In a new, large, transdiagnostic youth sample and multidomain high-dimension data, we used 160 candidate predictors encompassing neural, prenatal, developmental, physiologic, sociocultural, environmental, emotional and cognitive features and leveraged three different machine learning algorithms optimized with a novel artificial intelligence meta-learning technique to predict individual cases of anxiety, depression, attention deficit, disruptive behaviors and post-traumatic stress. Our models tested well in unseen, held-out data (AUC ≥ 0.94). By utilizing a large-scale design and advanced computational approaches, we were able to compare the relative predictive ability of neural versus psychosocial features in a principled manner and found that psychosocial features consistently outperformed neural metrics in their relative ability to deliver robust predictions of individual cases. We found that deep learning with artificial neural networks and tree-based learning with XGBoost outperformed logistic regression with ElasticNet, supporting the conceptualization of mental illnesses as multifactorial disease processes with non-linear relationships among predictors that can be robustly modeled with computational psychiatry techniques. To our knowledge, this is the first study to test the relative predictive ability of these gold-standard algorithms from different classes across multiple mental health conditions in youth within the same study design in multidomain data utilizing >100 candidate predictors. Further research is suggested to explore these findings in longitudinal data and validate results in an external dataset.

Integrated Evolutionary Learning: An Artificial Intelligence Approach to Joint Learning of Features and Hyperparameters for Optimized, Explainable Machine Learning.

Artificial intelligence and machine learning techniques have proved fertile methods for attacking difficult problems in medicine and public health. These techniques have garnered strong interest for the analysis of the large, multi-domain open science datasets that are increasingly available in health research. Discovery science in large datasets is challenging given the unconstrained nature of the learning environment where there may be a large number of potential predictors and appropriate ranges for model hyperparameters are unknown. As well, it is likely that explainability is at a premium in order to engage in future hypothesis generation or analysis. Here, we present a novel method that addresses these challenges by exploiting evolutionary algorithms to optimize machine learning discovery science while exploring a large solution space and minimizing bias. We demonstrate that our approach, called integrated evolutionary learning (IEL), provides an automated, adaptive method for jointly learning features and hyperparameters while furnishing explainable models where the original features used to make predictions may be obtained even with artificial neural networks. In IEL the machine learning algorithm of choice is nested inside an evolutionary algorithm which selects features and hyperparameters over generations on the basis of an information function to converge on an optimal solution. We apply IEL to three gold standard machine learning algorithms in challenging, heterogenous biobehavioral data: deep learning with artificial neural networks, decision tree-based techniques and baseline linear models. Using our novel IEL approach, artificial neural networks achieved ≥ 95% accuracy, sensitivity and specificity and 45-73% R 2 in classification and substantial gains over default settings. IEL may be applied to a wide range of less- or unconstrained discovery science problems where the practitioner wishes to jointly learn features and hyperparameters in an adaptive, principled manner within the same algorithmic process. This approach offers significant flexibility, enlarges the solution space and mitigates bias that may arise from manual or semi-manual hyperparameter tuning and feature selection and presents the opportunity to select the inner machine learning algorithm based on the results of optimized learning for the problem at hand.