A single infusion in treatment-resistant depression was followed by symptom improvement and broader EEG resting-state connectivity in frontoparietal and default-mode networks.
Evidence
This intervention-linked EEG study measured source-based theta and beta resting-state connectivity in 24 participants with treatment-resistant depression before and 24 hours after 0.5 mg/kg racemic ketamine, with 34 healthy controls providing analogous non-intervention data.
Caveat
Symptom reduction was associated with baseline connectivity rather than connectivity change, and the small 24-hour design cannot define durability or causality of the connectivity findings.
Simplified
Treatment-resistant depression (TRD) accounts for approximately 30% of major depressive disorder cases and has been characterized by altered functional connectivity within and between the Default Mode (DMN) and Frontoparietal networks (FPN). can be an effective treatment for TRD, and its antidepressant response has been associated with alterations in (rsFC). Here, we evaluated the effect of a single subanesthetic dose of racemic ketamine (0.5 mg/kg) on electroencephalogram (EEG) derived source-based measures of rsFC from 24 participants with TRD (16 women; aged 44.35 ± 15.86 years). Ninety-six channel resting state EEG data were collected 24 h before and after ketamine infusion. Exact low-resolution electromagnetic tomography (eLORETA) was used to estimate theta and beta-band rsFC within and between the DMN and FPN. Ruminative symptoms were assessed using the Ruminative Response Scale. Analogous data were collected from 34 healthy control participants (25 women, aged 32.49 ± 14.07 years) who did not receive any intervention. Twenty-four hours post-infusion, depressive, anhedonic, and ruminative symptoms for the TRD sample were significantly reduced. Interestingly, symptom reduction was not correlated with any changes in rsFC but was associated with initial pre-ketamine rsFC. Moreover, individuals with TRD displayed broad increases in rsFC within the DMN and FPN as well as between these two networks. Based on preclinical findings, we posit that ketamine's synaptogenic effects may be driving this general increase in connectivity. However, these synaptogenic effects can be short lived, and future work probing the full time-course of rsFC via EEG pre- and post-ketamine administration is warranted.
Key numbers
24
Participants with TRD
Total number of participants with treatment-resistant depression in the study.
34
Healthy control participants
Total number of healthy control participants in the study.
46%
Significant symptom reduction
Percentage of individuals with a more than 50% reduction in symptoms after infusion.
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