Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 May 15:287:247-254.
doi: 10.1016/j.jad.2021.03.034. Epub 2021 Mar 19.

Cortisol effects on brain functional connectivity during emotion processing in women with depression

Charlene N Rivera-Bonet  1 , Rasmus M Birn  2 , Charlotte O Ladd  3 , Mary E Meyerand  4 , Heather C Abercrombie  5
Affiliations
Randomized Controlled Trial

Cortisol effects on brain functional connectivity during emotion processing in women with depression

Charlene N Rivera-Bonet et al. J Affect Disord. .

Abstract

Background: Depression is associated with altered functional connectivity and altered cortisol sensitivity, but the effects of cortisol on functional connectivity in depression are unknown. Previous research shows that brief cortisol augmentation (CORT) has beneficial neurocognitive effects in depression.

Methods: We investigated the effects of CORT (20mg oral cortisol) on functional connectivity during emotion processing in women with depression. Participants included 75 women with no depression or a depressive disorder. In a double-blind, crossover study, we used functional magnetic resonance imaging to measure effects of CORT vs. placebo on task-based functional connectivity during presentation of emotionally-laden images. We performed psychophysiological interaction (PPI) to test interactions among depression severity, cortisol administration, and task-dependent functional connectivity using the hippocampus and amygdala as seeds.

Results: During the presentation of negative images, CORT (vs. placebo) increased functional connectivity between the hippocampus and putamen in association with depression severity. During the presentation of positive pictures CORT increased functional connectivity between the hippocampus and middle frontal gyrus as well as superior temporal gyrus in association with depression.

Limitations: Because cortisol was pharmacologically manipulated, results cannot be extrapolated to endogenous increases in cortisol levels. The sample did not permit investigation of differences due to race, ethnicity, or sex. Co-morbidities such as anxiety or PTSD were not accounted for.

Conclusions: The results suggest that CORT has normalizing effects on task-dependent functional connectivity in women with depression during emotion processing. Increasing cortisol availability or signaling may have therapeutic benefits within affective disorders.

Keywords: Cortisol; Depression; Emotion Processing; Hippocampus; Psychophysiological interaction; Task-based functional connectivity.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Study timeline.
Participants were screened to determine eligibility, after which they underwent a mock MRI scan for acclimation. On days 1 and 8 of the study, participants completed an emotion task during fMRI scanning. Participants received either placebo or 20mg cortisol (order randomized and double-blinded) 90 minutes before the emotion task administered during fMRI scanning.
Figure 2.
Figure 2.. Effects of cortisol on hippocampal functional connectivity during presentation of negative pictures.
Psychophysiological interactions were tested to investigate task-dependent functional connectivity during negative pictures in relation to depression severity. (A) The right hippocampus (30, −24, −9) was selected as region of interest. (B1) During the presentation of negative IAPS pictures, administration of cortisol increased functional connectivity between the right hippocampus and the left putamen (22, −4, −4; p>0.005; ∝ = 0.03). There were no significant differences in functional connectivity with the left hippocampus as a seed region. (B2) Boxplots for illustration purposes depict correlation coefficients extracted for the putamen (in relation to hippocampus) and compared between no depression and current depression groups. Cortisol administration increased functional connectivity in relation to depression severity. R= right; L=left.
Figure 3.
Figure 3.. Effects of cortisol on hippocampal functional connectivity during presentation of positive pictures.
Psychophysiological interactions were tested to investigate task-dependent functional connectivity during positive pictures in relation to depression severity. (A) Bilateral hippocampus (right= 30, −24, −9; left= −30, −24, −9) was chosen as a seed region. (B1) During the presentation of positive IAPS images, cortisol administration increased functional connectivity between bilateral hippocampus and the superior temporal gyrus (66, 28, 14; p>0.005, ∝ = 0.01) and the (C1) middle frontal gyrus (12, 18, 60). Boxplots for illustration purposes depict correlation coefficients extracted for the (B2) medial frontal gyrus and the (C2) temporal lobe and compared between no depression and current depression groups. Cortisol administration increased functional connectivity in association with depression severity. BL=bilateral; L=left.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abercrombie HC, Frost CP, Walsh EC, Hoks RM, Cornejo MD, Sampe MC, Gaffey AE, Plante DT, Ladd CO, Birn RM, 2018. Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 3, 274–284. 10.1016/j.bpsc.2017.11.005 - DOI - PMC - PubMed
    1. Abercrombie HC, Jahn AL, Davidson RJ, Kern S, Kirschbaum C, Halverson J, 2011. Cortisol’s effects on hippocampal activation in depressed patients are related to alterations in memory formation. J. Psychiatr. Res 45, 15–23. 10.1016/j.jpsychires.2010.10.005 - DOI - PMC - PubMed
    1. Admon R, Holsen LM, Aizley H, Remington A, Whitfield- S, Goldstein JM, Pizzagalli DA, Hospital M, Biology G, Hospital W, Hospital W, Hospital MG, Sciences C, Hospital M, 2016. Striatal hyper-sensitivity during stress in remitted individuals with recurrent depression Roee. Biol. Psychiatry 78, 67–76. 10.1016/j.biopsych.2014.09.019.Striatal - DOI - PMC - PubMed
    1. Albouy G, Fogel S, King BR, Laventure S, Benali H, Karni A, Carrier J, Robertson EM, Doyon J, 2015. Maintaining vs. enhancing motor sequence memories: Respective roles of striatal and hippocampal systems. Neuroimage 108, 423–434. 10.1016/j.neuroimage.2014.12.049 - DOI - PubMed
    1. Albouy G, Sterpenich V, Balteau E, Vandewalle G, Desseilles M, Dang-Vu T, Darsaud A, Ruby P, Luppi P-H, Degueldre C, Peigneux P, Luxen A, Maquet P, 2008. Both the Hippocampus and Striatum Are Involved in Consolidation of Motor Sequence Memory. Neuron 58, 261–272. 10.1016/j.neuron.2008.02.008 - DOI - PubMed

Publication types