Cortisol, moderated by age, is associated with antidepressant treatment outcome and memory improvement in Major Depressive Disorder: A retrospective analysis

Felipe A Jain; Colm G Connolly; Victor I Reus; Dieter J Meyerhoff; Tony T Yang; Synthia H Mellon; Scott Mackin; Christina M Hough; Alexandra Morford; Owen M Wolkowitz

doi:10.1016/j.psyneuen.2019.104386

Cortisol, moderated by age, is associated with antidepressant treatment outcome and memory improvement in Major Depressive Disorder: A retrospective analysis

Psychoneuroendocrinology. 2019 Nov:109:104386. doi: 10.1016/j.psyneuen.2019.104386. Epub 2019 Jul 26.

Authors

Affiliations

¹ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: felipe.jain@post.harvard.edu.
² Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: colmconn@gmail.com.
³ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: victor.reus@ucsf.edu.
⁴ Department of Radiology and Biomedical Imaging, University of California, 505 Parnassus Avenue, San Francisco, CA, 94143, USA; Center for Imaging of Neurodegenerative Diseases, VA Medical Center, 4150 Clement St., San Francisco, CA 94121, USA. Electronic address: dieter.meyerhoff@ucsf.edu.
⁵ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: tony.yang@ucsf.edu4.
⁶ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, 505 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: sindy.mellon@ucsf.edu.
⁷ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: scott.mackin@ucsf.edu.
⁸ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: cmhough@ucla.edu.
⁹ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: amorf19@gmail.com.
¹⁰ Weill Institute for Neurosciences, Department of Psychiatry, University of California, 401 Parnassus Avenue, San Francisco, CA, 94143, USA. Electronic address: owen.wolkowitz@ucsf.edu.

Abstract

Background: Studies testing the relationship between cortisol levels, depression, and antidepressant treatment response have yielded divergent results suggesting the possibility of moderators of a cortisol effect. Several studies indicate that age may moderate the relationship between cortisol and depression. In patients with Major Depressive Disorder (MDD), we studied the interactive effects of age and cortisol in association with MDD diagnostic status and mood and memory response to antidepressant treatment.

Methods: Serum cortisol levels in 66 unmedicated patients with MDD and 75 matched healthy controls (HC) were measured at baseline and retrospectively analyzed. Logistic regression was used to determine an association of age, cortisol and their interaction with MDD diagnosis in the pooled sample of MDD and HC participants. Thirty-four of the MDD participants (age range: 19-65 years; median: 36) underwent treatment with a selective serotonin reuptake inhibitor (SSRl) for 8 weeks. Clinician and self-ratings of depression symptoms, as well as tests of verbal and visual delayed recall were obtained at baseline and post treatment. Moderation analyses determined the effect of age on the relationship between baseline cortisol and treatment outcome.

Results: Cortisol, moderated by age, was associated with MDD diagnosis (p < .05), treatment-associated reduction of depression symptoms (p < .001) and improvement of delayed recall (p < .001). Modeling the Cortisol × Age interaction suggested that for participants below the median age of our sample, lower cortisol levels were associated with a lower rate of MDD diagnosis and higher antidepressant effects. On the contrary, in those above the median sample age, lower cortisol was associated with a higher rate of MDD and less improvement in depression symptoms and memory performance.

Conclusions: Our results add to the body of literature suggesting that age might be an important factor in moderating the relationship between peripheral cortisol levels, depression, cognition, and prognosis. These results indicate that previous disparities in the literature linking peripheral cortisol levels with depression characteristics and treatment response may critically relate, at least in part, to the age of the participants studied.

Keywords: Aging; Antidepressants; Cortisol; HPA axis; Major Depressive Disorder; Memory.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Age Factors
Antidepressive Agents / therapeutic use
Case-Control Studies
Cognition / drug effects
Depression / metabolism
Depressive Disorder, Major / metabolism*
Depressive Disorder, Major / physiopathology
Female
Humans
Hydrocortisone / analysis
Hydrocortisone / metabolism*
Hypothalamo-Hypophyseal System / drug effects
Male
Memory / physiology*
Middle Aged
Pituitary-Adrenal System / drug effects
Retrospective Studies
Selective Serotonin Reuptake Inhibitors / pharmacology
Treatment Outcome*

Substances

Antidepressive Agents
Serotonin Uptake Inhibitors
Hydrocortisone

Abstract

Publication types

MeSH terms

Substances

Grants and funding