Abstract Depression is common, costly, and a leading cause of disability. Assessment of behavior and experience related to depression has tended to rely on self-report and interview-based methods. Environmental momentary assessment inserts assessment into people's lives, but still requires active engagement by those being evaluated. We propose to develop and validate a mobile phone-based personal sensing system to detect depression and related behaviors that relies on sensor data that are collected continuously and unobtrusively. Because people tend to keep their phones with them, the mobile phone is an ideal sensing platform, as it can continuously collect data in the context of the individual's life with no ongoing effort on the part of the user. Such systems are already being used to detect simple behaviors, such as activity recognition and sleep quantification, which are more proximal to the sensor data. Aim 1 will develop markers for a broad range of behavioral targets related to symptoms of major depressive episode (MDE; anhedonia, negative mood, sleep disruption, psychomotor activity, fatigue, and diminished concentration) and related domains (e.g. social functioning, stress, motivation) across a representative sample of participants. Aim 2 will combine all behavioral targets using machine learning to 1) estimate MDE and symptom severity cross-sectionally, 2) identify transition from non-depressed to depressed states, and depressed to non-depressed states, and 3) predict MDE and symptom severity 4 and 8 weeks out. Aim 3 will seek to understand the complex relationships among behavioral targets and depression. We will accomplish this by enrolling 1200 representative participants, in six 4-month waves of data collection. Each participant will download software that collects a wide variety of sensor data (GPS, accelerometry, light, Bluetooth, phone usage, etc.) and an app that collects ecological momentary assessments (EMA). Following each wave we will develop algorithms for a subset of behavioral targets and features (a definition of raw sensor data that incorporates meaning, like translating GPS data into “home”). Each algorithm will then be validated in the subsequent wave. After 5 waves (1000 participants), the set of all markers of behavioral targets and features will be combined using machine learning to detect and predict depression. This hierarchical approach extracts information from data at multiple levels, which ultimately is far more likely to succeed than relying solely on raw sensor data. The final wave will serve to replicate and validate the entire depression prediction model. This sensing platform is scientifically significant, as it will provide a fundamentally new tool for obtaining continuous, objective markers of behavior that are relevant to depression, as well as many other psychiatric and medical disorders. This project has the potential develop new understandings into the etiology of depression. It is clinically signi...