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Cerebral perfusion in depression: Relationship to sex, dehydroepiandrosterone sulfate and depression severity


Ritter, Christopher; Buchmann, Andreas; Müller, Sabrina Theresia; Hersberger, Martin; Haynes, Melanie; Ghisleni, Carmen; Tuura, Ruth; Hasler, Gregor (2021). Cerebral perfusion in depression: Relationship to sex, dehydroepiandrosterone sulfate and depression severity. NeuroImage: Clinical, 32:102840.

Abstract

BACKGROUND

Major depressive disorder (MDD) is a leading cause of disease burden and shows a marked sexual dimorphism. Previous studies reported changes in cerebral perfusion in MDD, an association between perfusion and dehydroepiandrosterone sulfate (DHEAS) levels, and large sex differences in perfusion. This study examines whether perfusion and DHEAS might mediate the link between sex and depressive symptoms in a large, unmedicated community sample.

METHODS

The sample included 203 healthy volunteers and 79 individuals with past or current MDD. Depression severity was assessed with the Hamilton Depression Scale (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS). 3 T MRI perfusion data were collected with a pseudocontinuous arterial spin labelling sequence and DHEAS was measured in serum by LC-MS/MS.

RESULTS

Large sex differences in perfusion were observed (p < 0.001). Perfusion was negatively correlated with DHEAS (r = -0.23, p < 0.01, n = 250) and with depression severity (HAM-D: r = -0.17, p = 0.01, n = 242; partial Spearman correlation, controlling for age and sex), but not with anxiety. A significant sex*perfusion interaction on depression severity was observed. In women, perfusion showed more pronounced negative correlations with depressive symptoms, with absent or, in the case of the MADRS, opposite effects observed in men. A mediation analysis identified DHEAS and perfusion as mediating variables influencing the link between sex and the HAM-D score.

CONCLUSION

Perfusion was linked to depression severity, with the strongest effects observed in women. Perfusion and the neurosteroid DHEAS appear to mediate the link between sex and HAM-D scores, suggesting that inter-individual differences in perfusion and DHEAS levels may contribute to the sexual dimorphism in depression.

Abstract

BACKGROUND

Major depressive disorder (MDD) is a leading cause of disease burden and shows a marked sexual dimorphism. Previous studies reported changes in cerebral perfusion in MDD, an association between perfusion and dehydroepiandrosterone sulfate (DHEAS) levels, and large sex differences in perfusion. This study examines whether perfusion and DHEAS might mediate the link between sex and depressive symptoms in a large, unmedicated community sample.

METHODS

The sample included 203 healthy volunteers and 79 individuals with past or current MDD. Depression severity was assessed with the Hamilton Depression Scale (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS). 3 T MRI perfusion data were collected with a pseudocontinuous arterial spin labelling sequence and DHEAS was measured in serum by LC-MS/MS.

RESULTS

Large sex differences in perfusion were observed (p < 0.001). Perfusion was negatively correlated with DHEAS (r = -0.23, p < 0.01, n = 250) and with depression severity (HAM-D: r = -0.17, p = 0.01, n = 242; partial Spearman correlation, controlling for age and sex), but not with anxiety. A significant sex*perfusion interaction on depression severity was observed. In women, perfusion showed more pronounced negative correlations with depressive symptoms, with absent or, in the case of the MADRS, opposite effects observed in men. A mediation analysis identified DHEAS and perfusion as mediating variables influencing the link between sex and the HAM-D score.

CONCLUSION

Perfusion was linked to depression severity, with the strongest effects observed in women. Perfusion and the neurosteroid DHEAS appear to mediate the link between sex and HAM-D scores, suggesting that inter-individual differences in perfusion and DHEAS levels may contribute to the sexual dimorphism in depression.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Life Sciences > Neurology
Health Sciences > Neurology (clinical)
Life Sciences > Cognitive Neuroscience
Language:English
Date:28 September 2021
Deposited On:12 Nov 2021 17:07
Last Modified:25 Apr 2024 01:40
Publisher:Elsevier
ISSN:2213-1582
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.nicl.2021.102840
PubMed ID:34628302
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)