Research projects of Domain A ("Trajectories")

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Domain A: Description of antecedents and trajectories of losing and regaining control and modulating factors

In this domain, we will assess the trajectories of losing and regaining control and elucidate how triggers and modulating factors interact and predict when subjects with mild to moderate alcohol use disorder (AUD) lose or regain control over drug intake. We will identify common, as well as age- and gender-specific mechanisms that contribute to losing and regaining control over consumption of alcohol by systematically assessing a large cohort of persons with severity levels of AUD, who do not (yet) require detoxification. We will use Ambulatory Assessment, including Ecological Momentary Assessment, to acquire intensive longitudinal datasets over several months in AUD patients with and without additional tobacco and cannabis use. This will allow us to observe longitudinal trajectories with respect to losing and regaining control over drug intake in real life situations.

  • Structure and sequence of the projects in domain A

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Project A01: Longitudinal monitoring of triggers and modifying factors in human addiction

The principal aim of this prospective longitudinal cohort study is to examine individual-level predictors of trajectories of losing and regaining control over alcohol intake across lifespan in real life using ambulatory assessment. We will assess individual differences in behavior, neurobiological correlates and polygenic risk scores in adolescents and young adults (N = 300; WP1) as well as early (N = 300; WP2) and late middle-aged adults (N = 300; WP3) with alcohol use disorder (AUD) over the course of one year. This will allow us to identify individual-level differences (using latent growth curve models) and profiles (using latent growth mixture models) that predict regaining or losing control, which will provide critical input for novel prevention and intervention strategies.

Principal Investigators:
Prof. Dr. Dr. Tobias Banaschewski, Medical Faculty Mannheim
Prof. Dr. Dr. Andreas Heinz, Charité - Universitätsmedizin Berlin
Prof. Dr. Dr. Michael Rapp, University of Potsdam

Project members:
Friederike Deeken, University of Potsdam
Patricia Pelz, Charité - Universitätsmedizin Berlin
Friederike Wedemeyer, Charité - Universitätsmedizin Berlin
Julia Wenzel, Charité - Universitätsmedizin Berlin

Project A02: Longitudinal monitoring of cognitive control as a modifying factor of drinking behavior

The implicit assumption that intra-individual changes in cognitive control and decision-making are reflected by changes in real-life drinking behavior remains largely untested. We aim to identify differential cognitive trajectories related to losing and regaining control over everyday drinking behavior. We will investigate this by using a smartphone application for the longitudinal ambulatory assessment of cognitive control and decision-making.

Principal Investigators:
Dr. Lorenz Deserno, University College London, Technische Universität Dresden
Prof. Dr. Michael Smolka, Technische Universität Dresden

Project member:
Ying Lee, Technische Universität Dresden

Project A03: Stress-related predictor profiles for craving and relapse in human addiction

This project will investigate stress- and alcohol cue-related physiological markers in a lab experiment to assess interactions between acute psychological vs. physical stress exposure and alcohol cue-exposure regarding their effects on (1) alcohol craving and related markers, (2) their predictive capacity for future alcohol intake in a real-life setting, and (3) the identification of their neural correlates in brain circuits of motivational, cognitive, and affective processing. Our long-term aim is the definition of a setup of mobile sensors and their integration in a mobile infrastructure that allows the prediction of stress related alcohol intake in an ambulatory setting.
 

Principal Investigators:
Prof. Dr. Falk Kiefer, Zentralinstitut für Seelische Gesundheit Mannheim
Prof. Dr. Clemens Kirschbaum, Technische Universität Dresden
Prof. Dr. Jan Stallkamp, Fraunhofer Institute for Manufacturing Engineering and Automation, Mannheim

Project members:
Dr. Patrick Bach, Zentralinstitut für Seelische Gesundheit Mannheim
Dr. Jens Langejürgen, Fraunhofer Institute for Manufacturing Engineering and Automation
Philipp Radler, Fraunhofer Institute for Manufacturing Engineering and Automation
Prof. Dr. Sabine Vollstädt-Klein, Zentralinstitut für Seelische Gesundheit Mannheim
Judith Zaiser, Zentralinstitut für Seelische Gesundheit Mannheim
Sina Zimmermann, Zentralinstitut für Seelische Gesundheit Mannheim

Project A04: Intense characterization of triggers, modifying factors and mechanisms at course transition points in human addiction

The project will use ambulatory assessment and functional neuroimaging to identify triggers, modifying factors and intermediate neural mechanisms in alcohol use disorder (AUD) in course phases with a substantial increase or decrease in alcohol consumption, respectively. We will assess temporally highly resolved ambulatory assessment for six weeks to identify intraindividual differences in in the momentary effects of triggers and modifying factors on subjective craving, mood, impulsivity and alcohol consumption. We will further identify their neural correlates in brain circuits relevant for cognitive, affective and motivational processing and test the predictive value of the identified mechanisms for subsequent disease trajectories to critically inform novel prevention and intervention strategies.

Principal Investigators:
Prof. Dr. Ulrich Ebner-Priemer, Karlsruhe Institute of Technology
Prof. Dr. Christine Heim, CharitéUniversitätsmedizin Berlin
Prof. Dr. Dr. Heike Tost, Zentralinstitut für Seelische Gesundheit Mannheim

Project members:
Dr. Gabriela Gan, Zentralinstitut für Seelische Gesundheit Mannheim
Mirjam Melzer, Zentralinstitut für Seelische Gesundheit Mannheim

Project A05: Intensive behavioral monitoring and dynamical state transitions in animal models of addiction

Using novel approaches established in statistical physics and dynamical systems, we will investigate whether early warning signs that are indicative of critical state transitions into addictive behavior can be detected by intensive longitudinal data (ILD) derived from a rat model for alcohol addiction and from a long-term nicotine self-administration model.

Principal Investigators:
PD Dr. Dr. Hamid Noori, Max Planck Institute for Biological Cybernetics Tübingen, Zentralinstitut für Seelische Gesundheit Mannheim
Prof. Dr. Rainer Spanagel, Zentralinstitut für Seelische Gesundheit Mannheim

Project A06: AI-based predictive neuro-behavioral modeling of individual trajectories in addiction

Our project aims at inferring subject-level recurrent neural network (RNN) models of behavioral dynamics from multi-modal mobile data. We will develop methods that integrate data obtained from different modalities (such as EMA, accelerometer etc.) and follow distinct probability distributions and sampling rates. This framework will be applied to data from A01-A04 to identify and predict dynamical transitions between regaining & losing control, predict long-term trajectories, and identify subgroups based on inferred RNN parameters. Lastly, we aim at identifying crucial factors and drivers behind these transitions, as well as mechanisms governing the behavioral dynamics.

Principal Investigators:
Prof. Dr. rer. nat. Daniel Durstewitz, Zentralinstitut für Seelische Gesundheit Mannheim
Dr. sc. hum. Georgia Koppe, Zentralinstitut für Seelische Gesundheit Mannheim