Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex

K. Mareckova, L. Holsen, R. Admon, S. Whitfield-Gabrieli, L. J. Seidman, S. L. Buka, A. Klibanski, J. M. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

Background Maladaptive responses to negative affective stimuli are pervasive, including clinically ill and healthy people, and men and women respond differently at neural and hormonal levels. Inspired by the Research Domain Criteria initiative, we used a transdiagnostic approach to investigate the impact of sex and dysphoric mood on neural-hormonal responses to negative affective stimuli. Methods Participants included 99 individuals with major depressive disorder, psychosis and healthy controls. Functional magnetic resonance imaging (fMRI) was complemented with real-time acquisition of hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and task-related connectivity was assessed using generalized psychophysiological interaction. Results Across all participants, elevated cortisol response predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala connectivity. In those with worse dysphoric mood, elevated cortisol response predicted lower activity in hypothalamus and hippocampus. In women, elevated cortisol response was associated with lower activity in medial prefrontal cortex and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood, elevated cortisol response was associated with low hypothalamo–hippocampal connectivity. There were no interactions with diagnosis or medication. Limitations There was limited power to correct for multiple comparisons across total number of ROIs and connectivity targets; cortisol responses were relatively low. Conclusions We conclude that the pathophysiology in neural-hormonal responses to negative affective stimuli is shared across healthy and clinical populations and varies as a function of sex and dysphoric mood. Our findings may contribute to the development of hormonal adjunctive therapeutics that are sex-dependent, underscoring the importance of one's sex to precision medicine.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalJournal of Affective Disorders
Volume222
DOIs
StatePublished - Nov 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIMH R03 MH105585 and an anonymous donor fund (with original data collected in ORWH-NIMH P50 MH082679 and NIMH R01 MH56956 Phase III; JMG PI across studies). The research was also conducted with support from Harvard Catalyst and the Harvard Clinical and Translational Science Center (NIH #UL1 RR025758). For KM's time, we would like to thank the European Union who financed the Marie Curie Intra-European Fellowship for Career Development and The Ministry of Education, Youth and Sports of the Czech Republic / MEYS (CEITEC 2020; LQ1601).

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • Cortisol response
  • Dysphoric mood
  • FMRI
  • Negative affect
  • RDoC
  • Sex differences

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex'. Together they form a unique fingerprint.

Cite this