Abstract
BackgroundMajor 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. MethodsThe 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. ResultsLarge 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. ConclusionPerfusion 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.
Highlights
Major depressive disorder (MDD) represents one of the leading causes of global disease burden (Bruffaerts et al, 2012; Lopez & Murray, 1998; Üstün, Ayuso-Mateos, Chatterji, Mathers, & Murray, 2004; WHO, 2008), with reported lifetime prevalence rates between 10% and 30% (Kessler, McGonagle, Swartz, Blazer, & Nelson, 1993; Kruijshaar et al, 2005)
This study examines whether perfusion and dehydroepiandrosterone sulfate (DHEAS) might mediate the link between sex and depressive symptoms in a large, unmedicated community sample
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
Summary
Major depressive disorder (MDD) represents one of the leading causes of global disease burden (Bruffaerts et al, 2012; Lopez & Murray, 1998; Üstün, Ayuso-Mateos, Chatterji, Mathers, & Murray, 2004; WHO, 2008), with reported lifetime prevalence rates between 10% and 30% (Kessler, McGonagle, Swartz, Blazer, & Nelson, 1993; Kruijshaar et al, 2005). Previous studies revealed a link between perfusion and depression, reporting both increases and decreases in perfusion in frontal, striatal, and limbic regions in the context of MDD (Duhameau et al, 2010; Li et al, 2018; Lui et al, 2009; Orosz et al, 2012; Vasic et al, 2015). Another recent study found reduced cerebral blood flow (CBF) in the right parahippocampal gyrus, the thalamus, and fusiform and middle temporal gyri as well as the bilateral insula, and increased CBF in the bilateral inferior parietal lobules in depressed adults (Cooper et al, 2019a). Perfusion and the neurosteroid DHEAS appear to mediate the link between sex and HAM-D scores, suggesting that interindividual differences in perfusion and DHEAS levels may contribute to the sexual dimorphism in depression
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