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.

中文翻译：

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抑郁症的脑灌注：与性别、硫酸脱氢表雄酮和抑郁症严重程度的关系

背景

重度抑郁症（MDD）是疾病负担的主要原因，并表现出明显的性别二态性。先前的研究报告了 MDD 中脑灌注的变化、灌注与硫酸脱氢表雄酮 (DHEAS) 水平之间的关联以及灌注的巨大性别差异。这项研究在大量未接受药物治疗的社区样本中检验了灌注和 DHEAS 是否可能介导性与抑郁症状之间的联系。

方法

样本包括 203 名健康志愿者和 79 名过去或当前患有 MDD 的人。使用汉密尔顿抑郁量表（HAM-D）和蒙哥马利-阿斯伯格抑郁量表（MADRS）评估抑郁严重程度。使用伪连续动脉自旋标记序列收集 3 T MRI 灌注数据，并通过 LC-MS/MS 测量血清中的 DHEAS。

结果

观察到灌注存在较大的性别差异（p < 0.001）。灌注与 DHEAS（r = -0.23，p < 0.01，n = 250）和抑郁严重程度呈负相关（HAM-D：r = -0.17，p = 0.01，n = 242；部分 Spearman 相关，控制年龄和性），但不伴有焦虑。观察到性*灌注对抑郁严重程度存在显着的相互作用。在女性中，灌注与抑郁症状呈更明显的负相关，而在男性中则没有观察到影响，或者在 MADRS 的情况下观察到相反的影响。中介分析确定 DHEAS 和灌注是影响性别和 HAM-D 评分之间联系的中介变量。

结论

灌注与抑郁症的严重程度相关，在女性中观察到的影响最强。灌注和神经类固醇 DHEAS 似乎介导性别和 HAM-D 评分之间的联系，这表明灌注和 DHEAS 水平的个体间差异可能导致抑郁症的性别二态性。