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Psychiatry Res Neuroimaging. 2017 Nov 30;269:1-8. doi: 10.1016/j.pscychresns.2017.09.001. Epub 2017 Sep 5.

Depression in chronic ketamine users: Sex differences and neural bases.

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Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Neuroscience, Yale University, New Haven, CT, USA; Beijing Huilongguan Hospital, Beijing, China. Electronic address:
Department of Psychiatry, Yale University, New Haven, CT, USA.
Bali Psychiatric Center, Ministry of Health and Welfare, Taiwan.
Department of Radiology, China Medical University Hospital, Taichung, Taiwan.
Institute of Cognitive Neuroscience, National Central University, Taoyuan, Taiwan; Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA.
Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan.
Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan. Electronic address:


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.


Depression; Ketamine; SUD; Sex difference; fMRI; rsFC; vmPFC

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