Breaking Away: The Role of Homeostatic Drive in Perpetuating Depression

Editor

Yan Q.

Department

Research

Document Type

Book Chapter

Publication Title

Psychoneuroimmunology. Methods in Molecular Biology

Abstract

We propose that the complexity of regulatory interactions modulating brain neurochemistry and behavior is such that multiple stable responses may be supported, and that some of these alternate regulatory programs may play a role in perpetuating persistent psychological dysfunction. To explore this, we constructed a model network representing major neurotransmission and behavioral mechanisms reported in literature as discrete logic circuits. Connectivity and information flow through this biobehavioral circuitry supported two distinct and stable regulatory programs. One such program perpetuated a depressive state with a characteristic neurochemical signature including low serotonin. Further analysis suggested that small irregularities in glutamate levels may render this pathology more directly accessible. Computer simulations mimicking selective serotonin reuptake inhibitor (SSRI) therapy in the presence of everyday stressors predicted recidivism rates similar to those reported clinically and highlighted the potentially significant benefit of concurrent behavioral stress management therapy.

First Page

121

Last Page

144

DOI

10.1007/978-1-4939-7828-1_8

Volume

1781

Publication Date

1-1-2018

Publisher

Humana Press, New York, NY

Medical Subject Headings

Brain (drug effects); Depressive Disorder (drug therapy, physiopathology); Glutamic Acid (metabolism); Homeostasis; Humans; Models, Neurological; Neural Pathways; Serotonin (metabolism); Serotonin Uptake Inhibitors (therapeutic use); Synaptic Transmission

PubMed ID

29705846

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