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

Chiang‐Shan R. Li, Sheng Zhang, Chia-Chun Hung, Chun-Ming Chen, Jeng-Ren Duann, Ching-Po Lin, Tony Szu-Hsien Lee

Psychiatry Research Neuroimaging November 30, 2017 DOI: 10.1016/j.pscychresns.2017.09.001 (opens in new tab)

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AI-extracted from the abstract
Characteristics Cross-sectional observational study Peer reviewed
Population Chronic ketamine users and non-drug-using healthy controls
Intervention Ketamine
Measures Center of Epidemiological Studies Depression Scale (CES-D)
Topics Depression Ketamine Esketamine
Keywords Sud Sex difference FMRI Rsfc Vmpfc
Key findings Chronic ketamine-using females, but not males, showed higher CES-D depression scores than healthy controls. Although sgACC connectivity did not differ significantly between groups at a corrected threshold, within ketamine users greater depression severity correlated with weaker sgACC-orbitofrontal cortex connectivity, and sex-specific correlations emerged with superior temporal gyrus in males and dorsomedial prefrontal cortex in females. The slopes of these connectivity-depression relationships differed significantly between ketamine users and controls.

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.

Comparable studies

Other cross-sectional and survey studies on ketamine for depression, most cited first.

Study Year Design Participants
Parental Attitudes Toward Use of Ketamine in Adolescent Mood Disorders and Suicidality English-speaking parents of adolescents 2021 Cross-sectional survey n = 283
A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study. Adults aged 18-74 years with treatment-resistant depression in Spain 2025 Observational, cross-sectional, retrospective study n = 196
Self-Reported Improvements in Comorbid Post-Traumatic Stress Disorder Symptoms, Depression, Anxiety, and Sleep Among Real-World Patients Receiving Medical Ketamine: Exploring the Role of Adjunct Therapies. Real-world patients with PTSD (n=98) and without PTSD (n=104) who received ketamine... 2025 Secondary analysis of survey data n = 202
Attitudes and Perceptions of Portuguese Psychiatrists and Psychologists on the Clinical Use of Ketamine. Portuguese psychiatrists and psychologists 2025 Cross-sectional survey n = 156
Efficacy of Electroconvulsive Therapy and Ketamine Therapy in Major Depressive Disorder; A Comparative Study Hospitalized patients with major depressive disorder 2023 Comparative cross-sectional study n = 40

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