Evidence map›Paper›PMID 42182572›Full record

ReviewNeuropsychiatric disease and treatment2026

The Fractalkine (FKN/CX3CL1) Pathway in Depression: A Critical Review of Its Role in Neuroinflammation and Therapeutic Potential.

ZhiLi YanLuan, Rula Sa, Yanting Fan, Huan Jia, Jianmiao Ge, Shuying Bai, RuiTing Ma, LiJun Tong

Abstract readReview
In one paragraph

Review in Neuropsychiatric disease and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

ZhiLi YanLuan *Mental Health College, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0008-9997-0459
Rula Sa *Departnent of Integrated Mongolian Western Medicine, Research Laboratory, Outpatient Department of Psychiatry, Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.
Yanting FanDepartnent of Integrated Mongolian Western Medicine, Research Laboratory, Outpatient Department of Psychiatry, Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0002-6313-7744
Huan JiaDepartnent of Integrated Mongolian Western Medicine, Research Laboratory, Outpatient Department of Psychiatry, Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0006-6436-3873
Jianmiao GeDepartnent of Integrated Mongolian Western Medicine, Research Laboratory, Outpatient Department of Psychiatry, Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0006-6739-4886
Shuying BaiDepartnent of Integrated Mongolian Western Medicine, Research Laboratory, Outpatient Department of Psychiatry, Inner Mongolia Autonomous Region Mental Health Center, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.
RuiTing MaMental Health College, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0002-5460-1808
LiJun TongMental Health College, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China.ORCID 0009-0003-4916-4962

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major Depressive Disorder (MDD), a global psychiatric disorder, involves complex pathogenesis in which neuroinflammation is considered one of the core pathophysiological processes. The fractalkine (FKN, CX3CL1)/CX3CR1 signaling pathway, a critical mediator of neuron-microglia communication, has been implicated in neuroinflammation and comorbid models depression, yet its precise and dynamic role in MDD remains controversial and insufficiently understood. This review aims to critically synthesize the existing literature to address these gaps. We first analyze the evidence for neuroinflammation in MDD, involving glial cells and pro-inflammatory cytokines. We then focus on the dual and context-dependent roles of the FKN/CX3CR1 pathway in regulating microglial function, synaptic plasticity, and inflammatory responses. Through a comparative analysis of existing literature, we suggest that neuroinflammation is a significant driver in the onset and progression of MDD, potentially engaging immune cells like microglia and astrocytes, and triggering the discharge of pro-inflammatory factors. The FKN/CX3CR1 pathway may play a dual role in regulating microglial function, maintaining synaptic homeostasis, and mediating inflammatory responses. Its dysregulation is potentially closely associated with inflammatory responses and synaptic damage in comorbid models, such as depression with diabetes and depression with rheumatoid arthritis. However, its specific role in MDD has not been fully elucidated, and direct evidence linking this pathway to major depressive disorder remains limited, as most current findings are derived from comorbid models or preclinical studies rather than clinical investigations. This review will systematically explore the general role of neuroinflammation in MDD, dissect the mechanisms of the FKN/CX3CR1 pathway in neuroinflammation and existing depression models, and prospectively potential therapeutic strategies and future research directions based on this pathway, thereby attempting to provide a new theoretical basis for the precision diagnosis and treatment of MDD.

Indexed as

FKN/CX3CR1major depressive disordermicroglianeuroinflammation

Identifiers

PMID42182572
PMCPMC13195038

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.