Antidepressant effect of an alkaloid extract from Annona cherimolia

Ketamine has been shown to be efficacious for the treatment of depression, specifically among individuals who do not respond to first-line treatments. There is still, however, a lack of clarity surrounding the clinical features and response periods across samples that respond to ketamine. This paper systematically reviews published randomized controlled trials that investigate ketamine as an antidepressant intervention in both unipolar and bipolar depression to determine the specific clinical features of the samples across different efficacy periods. Moreover, similarities and differences in clinical characteristics associated with acute versus longer-term drug response are discussed. Similarities across all samples suggest that the population that responds to ketamine’s antidepressant effect has experienced chronic, long-term depression, approaching ketamine treatment as a “last resort”. Moreover, differences between these groups suggest future research to investigate the potential of stronger efficacy towards depression in the context of bipolar disorder compared to major depression, and in participants who undergo antidepressant washout before ketamine administration. From these findings, suggestions for the future direction of ketamine research for depression are formed.

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Abnormal expression of rno_circRNA_014900 and rno_circRNA_005442 induced by ketamine in the rat hippocampus

BMC Psychiatry ◽

10.1186/s12888-019-2374-2 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Jing Mao ◽

Tianmei Li ◽

Di Fan ◽

Hongli Zhou ◽

Jianguo Feng ◽

...

Keyword(s):

Target Genes ◽

Circular Rna ◽

Fold Change ◽

Rat Hippocampus ◽

Antidepressant Effect ◽

Signal Pathways ◽

Qrt Pcr ◽

Abnormal Expression ◽

Reverse Transcription Pcr ◽

Pathway Analyses

Abstract Background Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. Methods The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p < 0.05). The results from the qRT-PCR showed that one of the circRNAs was significantly increased (rno_circRNA_014900; fold change = 2.37; p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. Conclusion Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.

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Immunoregulation and antidepressant effect of ketamine

Translational Neuroscience ◽

10.1515/tnsci-2020-0167 ◽

2021 ◽

Vol 12 (1) ◽

pp. 218-236

Author(s):

Nan Zhang ◽

Lihua Yao ◽

Peilin Wang ◽

Zhongchun Liu

Keyword(s):

Disease Burden ◽

Severe Disease ◽

Mental Health Disorder ◽

Antagonistic Effect ◽

Antidepressant Effect ◽

Future Research ◽

Recurrence Rates ◽

Aspartate Receptor ◽

Antidepressant Effects ◽

Common Mental Health Disorder

Abstract Major depressive disorder (MDD) is a common mental health disorder that brings severe disease burden worldwide. Traditional antidepressants are mainly targeted at monoamine neurotransmitters, with low remission rates and high recurrence rates. Ketamine is a noncompetitive glutamate N-methyl-d-aspartate receptor (NMDAR) antagonist, and its rapid and powerful antidepressant effects have come to light. Its antidepressant mechanism is still unclarified. Research found that ketamine had not only antagonistic effect on NMDAR but also strong immunomodulatory effect, both of which were closely related to the pathophysiology of MDD. Although there are many related studies, they are relatively heterogeneous. Therefore, this review mainly describes the immune mechanisms involved in MDD and how ketamine plays an antidepressant role by regulating peripheral and central immune system, including peripheral inflammatory cytokines, central microglia, and astrocytes. This review summarizes the related research, finds out the deficiencies of current research, and provides ideas for future research and the development of novel antidepressants.

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