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  Stress, sex hormones, inflammation, and major depressive disorder: Extending social signal transduction theory of depression to account for sex differences in mood disorders

Slavich, G. M., & Sacher, J. (2019). Stress, sex hormones, inflammation, and major depressive disorder: Extending social signal transduction theory of depression to account for sex differences in mood disorders. Psychopharmacology, 236(10), 3063-3079. doi:10.1007/s00213-019-05326-9.

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Slavich, George M.1, Author
Sacher, Julia2, Author           
1Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA, ou_persistent22              
2Minerva Research Group EGG (Emotion & neuroimaGinG) Lab, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_3230775              


Free keywords: Cytokines; Depression; Disease; Inflammation; Life stress; Neuroinflammation; Risk; Sex differences; Sex hormones; Social threat
 Abstract: Social Signal Transduction Theory of Depression is a biologically plausible, multi-level theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental adversity with internal biological processes that drive depression pathogenesis, maintenance, and recurrence. Central to this theory is the hypothesis that interpersonal stressors involving social threat (e.g., social conflict, evaluation, rejection, isolation, and exclusion) upregulate inflammatory processes that can induce several depressive symptoms, including sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. The original article describing this formulation (Psychol Bull 140:774-815, 2014) addressed critical questions involving depression onset and recurrence, as well as why depression is strongly predicted by early life stress and comorbid with anxiety disorders and certain physical disease conditions, such as asthma, rheumatoid arthritis, chronic pain, and cardiovascular disease. Here, we extend the theory to help explain sex differences in depression prevalence, which is a defining feature of this disorder. Central to this extension is research demonstrating that ovarian hormone fluctuations modulate women's susceptibility to stress, brain structure and function, and inflammatory activity and reactivity. These effects are evident at multiple levels and are highly context-dependent, varying as a function of several factors including sex, age, reproductive state, endogenous versus exogenous hormones, and hormone administration mode and dose. Together, these effects help explain why women are at greater risk for developing inflammation-related depressed mood and other neuropsychiatric, neurodevelopmental, and neurodegenerative disorders during the reproductive years, especially for those already at heightened risk for depression or in the midst of a hormonal transition period.


Language(s): eng - English
 Dates: 2018-10-102019-07-082019-07-292019-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/s00213-019-05326-9
PMID: 31359117
Other: Epub ahead of print
 Degree: -



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Project name : -
Grant ID : -
Funding program : Branco Weiss Fellowship - Society in Science
Funding organization : ETH Zurich
Project name : -
Grant ID : 25034 ; 25032
Funding program : NARSAD Young Investigator Award
Funding organization : Brain and Behavior Research Foundation
Project name : -
Grant ID : K08 MH103443
Funding program : -
Funding organization : National Institute of Mental Health (NIMH)
Project name : -
Grant ID : -
Funding program : Minerva Research Group Grant
Funding organization : Max Planck Society

Source 1

Title: Psychopharmacology
Source Genre: Journal
Publ. Info: Heidelberg : Springer-Verlag
Pages: - Volume / Issue: 236 (10) Sequence Number: - Start / End Page: 3063 - 3079 Identifier: ISSN: 0033-3158
CoNE: https://pure.mpg.de/cone/journals/resource/954925436478