Ernst Strüngmann Forum

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Intrusive Thinking

From Molecules to Free Will

Edited by Peter W. Kalivas and Martin P. Paulus

This wonderful book provides a comprehensive consideration of the very human experience of intrusive thinking. How such thoughts arise and their influence on behavior is covered by carefully crafted chapters from world-leading scientists. From cells to circuits, psychology to therapeutics, this is the definitive book on intrusive thinking.

Paul J. Kenny

Ward-Coleman Professor and Chair, Nash Family Department of Neuroscience, Mount Sinai School of Medicine, New York

Kalivas and Paulus have brought together a group of basic and clinical neuroscientists in order to synthesize the current knowledge and suggest future directions for a terribly understudied area: intrusive thoughts. This clinical phenomenon, though cutting across many diagnoses, is not a singular entity but quite heterogeneous. By bringing together the leading investigators in the field, they admirably summarize the state of the art, and presage future research directions.

Charles B. Nemeroff

Matthew P. Nemeroff Professor and Chair, Department of Psychiatry and Behavioral Sciences, the University of Texas at Austin

This lucidly written volume has contributions from some of the finest minds in neuroscience. Intrusive thoughts are salient in several psychiatric disorders and the book engagingly covers aspects ranging from pathophysiology to intervention. A tour de force!

Maria A. Oquendo

Ruth Meltzer Professor and Chairman of Psychiatry, Perelman School of Medicine, University of Pennsylvania

This highly original collection of articles by authoritative neuroscientists from multiple disciplines provides an extraordinary account of intrusive thoughts and, their impact on behavior and experience, as well as the underlying and varied neural mechanisms. The implications for psychiatric disorders and the potential interventions and treatments are thoughtfully considered. Kalivas and Paulus are to be congratulated in bringing this volume to fruition.

Barry J. Everitt

Emeritus Professor of Behavioural Neuroscience and Director of Research, University of Cambridge, UK

On any given day, unintended, recurrent thoughts intrude on our thinking and affect our behavior in ways that can be adaptive. Such thoughts, however, become intrusive and problematic when they are unwanted, become compulsive, or lead to socially or medically unacceptable behavior. This volume explores what goes on in our brains to create thought intrusions, and how these intrusions lead to maladaptive behavior.

Intrusive thoughts feature prominently in most psychiatric disorders, so understanding the neurological and behavioral processes underlying them is an urgent endeavor. To investigate these issues, contributors from a range of disciplines—including neuroscience, psychiatry, psychology, and pharmacology—consider the mechanisms involved in intrusive thoughts under normal and abnormal conditions. They analyze how decision making becomes corrupted to create uncontrollable intrusions, explore the implications for concepts of free will and individual responsibility, and suggest avenues for future research.

Contributors

Michael C. Anderson, Adam Aron, David Badre, Bernard W. T.Balleine, Marie Banich, Anya K. Bershad, Antonello Bonci, Michael B. Bonsall,Katheen T. Brady, Judson Brewer, Michael R. Bruchas, David M. Buss, Aurelio Cortese, Hugo D. Critchley, Damiaan Denys, Harriet de Wit, Lisa Espinosa, John R. Fedota, Shelly B. Flagel, Aikaterina Fotopoulou, Sophia Frangou, Karl Friston, Rita Z. Goldstein, Shannon L. Gourley, Suzanne N. Haber, Colleen A. Hanlon, Andreas Heinz, Emily A. Holmes, Quentin J. M, Huys, Peter W. Kalivas, Laura Kress, Hakwan Lau, Kayuet Liu, Tiago V. Maia, Lisa M. McTeague, Amy L. Milton, Marie Hélène Monfils, Martin P. Paulus, Paul E. M. Phillips, Marina R. Picciotto, Trevor W. Robbins, Angels C. Roberts, Daniela Schiller, Florian Schlagenhauf, Jonathan W. Schooler, Jens V. Schwarzbach, Jeremy K. Seamans, Laura Singh, Eliot A. Stein, Peter Tse, Renée M. Visser, Martin Voss

Intrusive Thinking across Neuropsychiatric Disorders

Peter W. Kalivas and Martin P. Paulus, Chairs

Program Advisory Committee

Katerina Fotopoulou, Rita Z. Goldstein, Peter W. Kalivas, Julia R. Lupp, Martin P. Paulus, Trevor W. Robbins, and Peter Tse

Background

Developing new treatments for neuropsychiatric diseases is a source of extreme frustration in both academic medicine and the pharmaceutical industry. Out of this a new approach has emerged based on the idea that symptoms driven by specific brain circuits are the best sources of new drug targets. By targeting individual symptoms, specific endophenotypes (symptoms that can be reliably measured and quantified) are studied, which may be shared across neuropsychiatric disorders. Circuit-based endophenotypes can be studied in animal models while full human psychiatric disorders cannot. Intrusive thinking is an exemplar endophenotype—one manifested in multiple neuropsychiatric disorders, all of which broadly impact medicine and society.

Defined as the sudden intrusion of unwanted or unwillful thoughts, images, or impulses, intrusive thinking is a frequent and natural occurrence within our stream of consciousness (Clark and Purdon 1995). An inability to control intrusive thinking can lead to a number of behavioral pathologies, including addiction disorders, posttraumatic stress disorder (PTSD), depression and obsessive-compulsive disorders (OCD). Importantly, the neural circuitry and cell biology in addiction models of intrusive thinking have been extensively characterized, and drugs targeting addictive drug-induced molecular changes within this circuitry have been shown to decrease intrusive thinking and some associated psychiatric disorders, including addiction, OCD, PTSD, and major depression. Thus, intrusive thinking is at the forefront of how the medical community will use endophenotypes to develop novel treatments and define psychiatric disorders.

There is a common perception that improving neuropsychiatric symptoms is a function of willpower. For instance, it is commonly believed that if patients exert sufficient willpower, they should be able to stop using drugs. Since intrusive thinking is defined as an inability to control one's thoughts and corresponding actions, it can be viewed as a failure of willpower. As such, the neurobiology of intrusive thinking speaks directly to the neurobiology of willpower. In addition to identifying how endophenotypes can best be used in neuropsychiatry, this Forum will work to expand the concept of an endophenotype: moving beyond its interpretation as a mechanism for developing novel medical treatments, to being an approach for how basic neurobiology can inform and impact societal interpretations of abnormal behavior.

Using intrusive thinking as an exemplar endophenotype, this Forum will explore how basic neurobiological/molecular dysfunctions revealed by the endophenotype approach can advance the discovery of neuropsychiatric treatments and lead to a broadening of social perspectives on psychiatric disorders. This core issue needs to be addressed to validate (or not) the use of endophenotypes as a strategy for developing new treatments for neuropsychiatric disorders and to determine whether the endophenotype construct can be sociologically extended to influence social norms. Answering this fundamental question speaks not only to a strategy for developing clinical cures, but to basic sociological and philosophical constructs of human behavior.

This Forum is supported by the Deutsche Forschungsgemeinschaft

The German Research Foundation

Goals for the Forum

To explore the mechanisms of intrusive thinking across multiple levels of analysis: cells, circuits, and psychological processes.
To examine the role of intrusive thinking as a core symptom across psychiatric disorders.
To identify promising interventions for treating intrusive thinking.
To consider societal and philosophical implications of intrusive thinking.

Group 1: Neural Mechanisms

What are the circuits that mediate extinction and intrusive thinking?
What is the state-of-the-art toolbox for how circuits mediate behavior?
What types of animal models can inform intrusive thinking?

Group 2: Interventions and Implications

What is the relationship between free will and intrusive thinking?
Is addiction a breakdown of free will?
What does 21st century neurobiology of free will look like?
Can intrusive thinking be a marker for addiction severity?
Can the process of translating intrusive thinking into treatments for neuropsychiatric diseases be developed into a template for progress in developing other endophenotypes for treating neuropsychiatric disorders?

Group 3: Neuropsychological Mechanisms of Intrusive Thinking

Current psychiatric perspectives on intrusive thinking
How can intrusive thinking be conceptualized at the level of psychological mechanisms?
How can intrusive thinking be measured in the lab and studied in the context of brain mechanisms?

Group 4: Systems

Neural networks relevant to psychopathology
Corticostriatal pathways of intrusion
Neural networks relevant to executive control systems and decision making

This Forum is supported by the Deutsche Forschungsgemeinschaft

The German Research Foundation