Depression, Adversity, and Stress Hormones (DASH) Study
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

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.
    


Intervention name(s): Cortisol; Placebo
Intervention type(s): Other; Other
Intervention description(s): We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.; We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.
Intervention MeSH terms: Hydrocortisone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Depression; Childhood Adversity; Childhood Abuse; Cortisol; Emotional Memory; Magnetic Resonance Imaging (MRI)