Abstract
Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system. Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field. Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16). Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers. Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.
Highlights
Major depressive disorder (MDD) and depressive episodes of bipolar disorder (BD), which have similar clinical presentations, are both types of mood disorders (McIntyre et al, 2019; Voḧ ringer and Perlis, 2016)
The search phrases associated with the kynurenine pathway (KP) included KYN and its key metabolites (e.g., kynurenic acid (KYNA), quinolinic acid (QUIN), 3-HK, and 3-hydroxyanthranilic acid (3-HAA)) (Figure 3A), and the phrases associated with mood disorders included depression and related disorders such as BD
The current analysis showed that the number of publications on the KP in mood disorders increased rapidly since 2006, a result possibly associated with the many active researchers in different disciplines (e.g., Authors “A–F”) with interests within this field, and several hotspots (e.g., QUIN) having occurred since
Summary
Major depressive disorder (MDD) and depressive episodes of bipolar disorder (BD), which have similar clinical presentations, are both types of mood disorders (McIntyre et al, 2019; Voḧ ringer and Perlis, 2016). They are both associated with high suicide rates and can pose large burdens to societies and economies, according to the Global Burden of Disease study (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018). Mood disorders can be characterized by a low-grade chronic proinflammatory state, possibly owing to pathophysiological dysfunctions in immune-inflammatory pathways; this state might induce brain functional and structural alterations via multiple mechanisms (Squassina et al, 2019). The metabolites of the KP, an important part of the microbiota-gutbrain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system
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