Depression, Adversity, and Stress Hormones (DASH) Study

Summary

The stress-related hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Basic research shows that cortisol modulates brain processes that are highly relevant to depression (especially the neural substrates of negative biases in learning and memory formation). However, very few studies have directly examined the effects of cortisol on neural circuitry of learning in depressed humans. In addition, the effects of cortisol on the neural substrates of learning differ for males and females. The toll of depression is especially high in women, who are roughly twice as likely as men to suffer from depression. Thus, the primary goal of this project is to investigate the effects of cortisol on the neural circuitry of learning in depressed women.

A secondary goal is to investigate whether early life adversity moderates cortisol's effects on the neural circuitry of learning. Animal data suggests that early life adversity causes life-long biases toward learning in threatening conditions associated with elevated cortisol. In addition, new data from humans suggests that alterations in cortisol traditionally ascribed to depression may stem in part from early adversity rather than depression per se. Thus, this study will examine effects of cortisol on the neural circuitry of learning in depressed and healthy women with and without history of early life adversity.

The study will use pharmacological manipulation of cortisol levels (compared to placebo) during measurement of brain activity at rest and during memory encoding of emotional and neutral stimuli. The study will also measure whether cortisol alters the negative biases in emotional memory often seen in depression. In doing so, the study will examine the role of cortisol in neural networks associated with emotional learning that are often implicated in depression.

Medications that target cortisol receptors in the brain may be beneficial in the treatment of depression. However, this knowledge has yet to inform clinical practice, and mechanisms of action of these medications are not well understood. This project is significant because it provides the prerequisite knowledge (and develops a paradigm) that can be used in the future in the development of more effective targeted intervention strategies.

Conditions

• Depression

Interventions

OTHER

Cortisol

We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.

OTHER

Placebo

We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• Brain & Behavior Research Foundation

  collaborator OTHER

• University of Wisconsin, Madison

  lead OTHER

Principal Investigators

• Heather C. Abercrombie, Ph.D. · University of Wisconsin School of Medicine & Public Health

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-07-31

Primary Completion

2016-05-19

Completion

2016-05-19