Background: Recently, an animal model for depression has shown that ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce.Methods: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis.Results: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders.Conclusions: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.
IntroductionSuicide is a serious problem worldwide and 90% cases are associated with pre-existing or underlying mental illness. As a common treatment for depressive symptoms that suicidal people may receive, selective serotonin reuptake inhibitors (SSRIs) have been linked to a possible increase in suicide rates. Studies focusing on SSRIs and suicide have produced inconsistent results, suggesting that use of SSRIs decreases, increases, has no effect on suicide rates, or that the effect of SSRIs on suicide is age-dependent. This protocol of network meta-analysis aims to precisely evaluate the time effects of SSRIs by observing weekly changes of suicidality in the first 2 months of the treatment, and consequently, to explore whether the effect of the SSRIs on suicide varies depending on the stages of the treatment; if so, we will identify the turning point.Methods and analysisWe will search in the following databases: PubMed, Web of science, China National Knowledge Infrastructure and Wanfang Data, from dates of inception to 9 July 2021, with language restricted to English and Chinese. Studies focusing on the time effect of SSRIs on suicide will be retrieved. Then, the study selection process will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, and the quality assessment will be conducted with Cochrane Collaboration’s tool. Two researchers will work independently on data extraction using a standardised data extraction spreadsheet. Any disagreement between two researchers will be discussed and determined by a third researcher.Ethics and disseminationThis work does not require ethics approval as it will be based on published studies. This review will be published in peer-reviewed journals.PROSPERO registration numberCRD42021244779.
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