Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

性别特异性神经生物学变化与重度抑郁症（MDD）有关。默认模式网络（DMN）、显着网络（SN）和额顶网络（FPN）的功能障碍是MDD的关键神经特征，然而，性别对MDD静息态网络动力学的潜在调节作用尚未得到充分评估。因此，我们从 138 名未接受药物治疗的首发 MDD 患者（55 名男性）和 243 名健康对照者（HC；106 名男性）中收集了静息态功能磁共振成像 (fMRI) 数据。提取重复的功能网络共激活模式 (CAP)、每个 CAP 花费的时间（与 CAP 关联的卷的总量）、持久性（与 CAP 关联的连续卷的平均数量）以及跨 CAP 的转换，涉及SN、DMN 和 FPN 被量化。相对于 HC，MDD 患者在涉及 DMN 激活和 FPN 失活（DMN + FPN-）的 CAP 中表现出更大的持久性。此外，相对于性别匹配的HC，男性MDD组在涉及SN和DMN的两个CAP（即DMN + SN-和DMN-SN +）中花费更多时间，并且更频繁地从DMN + FPN-CAP转变相对于男性 HC 组为 DMN + SN-CAP。相反，相对于女性 HC 组，女性 MDD 组在 DMN + SN-CAP 中表现出较低的持久性。我们的研究结果强调，SN 和 DMN 之间的不平衡可能是支持 MDD 性别差异的神经生物学标志。此外，DMN 的主导地位伴随着 FPN 的失活可能是与抑郁症相关的与性别无关的神经生物学相关性。