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Depression in chronic ketamine users: Sex differences and neural bases

机译：慢性氯胺酮的抑郁症：性别差异和神经基础

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Abstract Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users. Highlights ? Chronic ketamine misuse is associated with depression in women but not men. ? sgACC shows altered connectivity in link with depression in chronic ketamine users. ? Women and men differed in sgACC connectivity in accord with features of depression. ? Findings add to extant literature that has focused on the acute effects of ketamine.
机译：摘要长期使用氯胺酮会导致认知和情感缺陷，包括抑郁症。在这里，我们研究了慢性氯胺酮使用者的性别差异和抑郁的神经基础。根据流行病学研究中心抑郁量表（CES-D）的评估，与不使用药物的健康对照组（HC）相比，使用氯胺酮的女性（而非男性）的抑郁评分增加。我们评估了膝下前扣带回皮质（sgACC）的静息状态功能连通性（rsFC），sgACC是一种与抑郁症发病机制相关的前额叶结构。与HC相比，氯胺酮使用者（KU）在校正阈值下的sgACC连接度没有显著变化。然而，在KU，与CES-D评分的线性回归显示，随着抑郁症严重程度的增加，sgACC与眶额皮质（OFC）的连接减少。分别检查，男性和女性KU分别显示出与双侧颞上回和背内侧前额叶皮质（dmPFC）更高的sgACC连通性，与抑郁症相关。在KU和HC之间，sgACC OFC和sgACC dmPFC连接性与抑郁症的线性相关性在斜率上存在显著差异。这些发现强调了慢性氯胺酮使用者sgACC的rsFC变化与抑郁相关，以及这些变化中的性别差异。亮点？长期滥用氯胺酮与女性抑郁症有关，但与男性无关？sgACC显示慢性氯胺酮使用者的连通性改变与抑郁相关？根据抑郁症的特征，女性和男性在sgACC连通性方面存在差异？这些发现为关注氯胺酮急性效应的现有文献增添了新的内容。

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