A precision medicine approach for psychiatric disease based on repeated symptom scores.

For psychiatric diseases, rich information exists in the serial measurement of mental health symptom scores. We present a precision medicine framework for using the trajectories of multiple symptoms to make personalized predictions about future symptoms and related psychiatric events. Our approach fits a Bayesian hierarchical model that estimates a population-average trajectory for all symptoms and individual deviations from the average trajectory, then fits a second model that uses individual symptom trajectories to estimate the risk of experiencing an event. The fitted models are used to make clinically relevant predictions for new individuals. We demonstrate this approach on data from a study of antipsychotic therapy for schizophrenia, predicting future scores for positive, negative, and general symptoms, and the risk of treatment failure in 522 schizophrenic patients with observations over 8 weeks. While precision medicine has focused largely on genetic and molecular data, the complementary approach we present illustrates that innovative analytic methods for existing data can extend its reach more broadly. The systematic use of repeated measurements of psychiatric symptoms offers the promise of precision medicine in the field of mental health.

[1]  Elizabeth L. Ogburn,et al.  Statistical Reasoning and Methods in Epidemiology to Promote Individualized Health: In Celebration of the 100th Anniversary of the Johns Hopkins Bloomberg School of Public Health. , 2016, American journal of epidemiology.

[2]  S. Marder,et al.  Risperidone in the treatment of schizophrenia. , 1994, The American journal of psychiatry.

[3]  Elisa T. Lee,et al.  Statistical Methods for Survival Data Analysis , 1994, IEEE Transactions on Reliability.

[4]  H. Krumholz Big data and new knowledge in medicine: the thinking, training, and tools needed for a learning health system. , 2014, Health affairs.

[5]  Graeme L. Hickey,et al.  Joint Modelling of Multivariate Longitudinal Data and Time-to-Event Outcomes , 2016 .

[6]  Ewout W Steyerberg,et al.  Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers , 2011, Statistics in medicine.

[7]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[8]  R. Spitzer,et al.  The PHQ-9: validity of a brief depression severity measure. , 2001, Journal of general internal medicine.

[9]  Katherine E. Masyn,et al.  New approaches to studying problem behaviors: a comparison of methods for modeling longitudinal, categorical adolescent drinking data. , 2009, Developmental psychology.

[10]  B. Druss,et al.  Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. , 2015, JAMA psychiatry.

[11]  P. Zandi,et al.  Heterogeneity in long-term trajectories of depressive symptoms: Patterns, predictors and outcomes. , 2016, Journal of affective disorders.

[12]  Roy H Perlis,et al.  Abandoning personalization to get to precision in the pharmacotherapy of depression , 2016, World psychiatry : official journal of the World Psychiatric Association.

[13]  A Labelle,et al.  A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. , 1993, Journal of clinical psychopharmacology.

[14]  B. Löwe,et al.  Validation and Standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the General Population , 2008, Medical care.

[15]  Graeme L. Hickey,et al.  Joint modelling of time-to-event and multivariate longitudinal outcomes: recent developments and issues , 2016, BMC Medical Research Methodology.

[16]  S. R. Searle,et al.  Generalized, Linear, and Mixed Models , 2005 .

[17]  D. Rubin,et al.  Inference from Iterative Simulation Using Multiple Sequences , 1992 .

[18]  Conor V. Dolan,et al.  Factor analysis of variables with 2, 3, 5, and 7 response categories: A comparison of categorical variable estimators using simulated data , 1994 .

[19]  Scott L. Zeger,et al.  Generalized linear models with random e ects: a Gibbs sampling approach , 1991 .

[20]  E. Ziegel Statistical Methods for Survival Data Analysis , 1993 .

[21]  E. Ashley Towards precision medicine , 2016, Nature Reviews Genetics.

[22]  F. Collins,et al.  A new initiative on precision medicine. , 2015, The New England journal of medicine.

[23]  M. Karim Generalized Linear Models With Random Effects , 1991 .

[24]  Suchi Saria,et al.  A Framework for Individualizing Predictions of Disease Trajectories by Exploiting Multi-Resolution Structure , 2015, NIPS.

[25]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[26]  J. Weiner,et al.  Morbidity Trajectories as Predictors of Utilization: Multi-year Disease Patterns in Taiwan's National Health Insurance Program , 2011, Medical care.

[27]  K. Wardenaar,et al.  Symptom-specific course trajectories and their determinants in primary care patients with Major Depressive Disorder: Evidence for two etiologically distinct prototypes. , 2015, Journal of affective disorders.

[28]  David B. Dunson,et al.  Bayesian Data Analysis , 2010 .

[29]  K. McLaughlin,et al.  Developmental Trajectories of Anxiety and Depression in Early Adolescence , 2014, Journal of Abnormal Child Psychology.

[30]  G. Remington,et al.  Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia. , 2011, The British journal of psychiatry : the journal of mental science.

[31]  T. Vos,et al.  Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010 , 2013, The Lancet.

[32]  P. Diggle,et al.  Analysis of Longitudinal Data , 2003 .

[33]  W. Tschacher,et al.  Symptom trajectories in psychotic episodes. , 2002, Comprehensive psychiatry.

[34]  R. Spitzer,et al.  The PHQ-9 , 2001, Journal of General Internal Medicine.

[35]  H. Krumholz For A Learning Health System Big Data And New Knowledge In Medicine: The Thinking, Training, And Tools Needed , 2014 .