SynthesisPsychopharmacology2016
Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness.
Synthesis in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 347 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
347 citing papers in PubMed, 3 syntheses or guidelines pooled it, 684 citations in OpenAlex.
- Alterations of the endocannabinoid system in autism spectrum disorder: a systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2025Pooled it
- The role of the amygdala in depression: a bibliometric analysis (2015-2024).Frontiers in psychiatry · 2025Pooled it
- Validity of chronic restraint stress for modeling anhedonic-like behavior in rodents: a systematic review and meta-analysis.The Journal of international medical research · 2022Pooled it
- Early attachment disruption differentially enhances multiple signs of microglia activation in the prefrontal cortex, hippocampus, and preoptic area of periadolescent guinea pigs.Behavioural brain research · 2027Article
- Childhood adversity and psychotic-like experiences in adolescence: Investigating a pathway via disrupted pubertal and grey matter development.JCPP advances · 2026Article
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Impact of Imipenem on Cognitive Function, Anxiety-like Behaviour, Neurogenesis, and Astrogliosis in Pentylenetetrazol-Kindled Rats.Antibiotics (Basel, Switzerland) · 2026Article
- Pursuing the elusive biosignature for suicide: a decennial update.Molecular psychiatry · 2026Review
- Early-stage olfactory bulbectomy induces hyperlocomotion with increased astrocyte and microglial density in the prefrontal cortex of male rats.Brain structure & function · 2026Article
- Neuroinflammatory Mechanisms in Depression: From Biomarkers to Anti-Inflammatory Therapy.Brain sciences · 2026Review
- Intermittent fasting protects against stress-induced depression and demyelination via the gut microbiota-brain axis.Translational psychiatry · 2026Article
- Environmental enrichment as an intervention to prevent behavioral and neurobiological consequences of maternal separation in rodents: a scope review.Neurobiology of stress · 2026Article
- Ventromedial hypothalamus IL-6 signaling mediates the excessive aggressive behavior induced by late-gestational sleep deprivation in male mice.Behavioral and brain functions : BBF · 2026Article
- Review
- Observational
- The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data from the Hippocampus and Cortex.bioRxiv : the preprint server for biology · 2026Article
- Article
- Early life adversity increases striatal dopamine D1 receptor density and promotes social alcohol drinking in mice, especially males.Translational psychiatry · 2026Article
- ATP and major affective disorders: the involvement of P2X receptors in pathophysiology.Purinergic signalling · 2026Review
- Cross-Organ Neuroimmunology of Behavior.Annual review of immunology · 2026Review
287 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
rationalePsychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate this association. A number of preclinical studies have investigated the effect of stress on microglial activity. However, these have not been systematically reviewed before.
objectivesThis study aims to systematically review the effects of stress on microglia, as indexed by the histological microglial marker ionised calcium binding adaptor molecule 1 (Iba-1), and consider the implications of these for the role of stress in the development of mental disorders.
methodsA systematic review was undertaken using pre-defined search criteria on PubMed and EMBASE. Inclusion and data extraction was agreed by two independent researchers after review of abstracts and full text.
resultsEighteen studies met the inclusion criteria. These used seven different psychosocial stressors, including chronic restraint, social isolation and repeated social defeat in gerbils, mice and/or rats. The hippocampus (11/18 studies) and prefrontal cortex (13/18 studies) were the most frequently studied areas. Within the hippocampus, increased Iba-1 levels of between 20 and 200 % were reported by all 11 studies; however, one study found this to be a duration-dependent effect. Of those examining the prefrontal cortex, ∼75 % found psychosocial stress resulted in elevated Iba-1 activity. Elevations were also consistently seen in the nucleus accumbens, and under some stress conditions in the amygdala and paraventricular nucleus.
conclusionsThere is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions. These effects were seen with early-life/prenatal stress, as well as stressors in adulthood. We consider these findings in terms of the two-hit hypothesis, which proposes that early-life stress primes microglia, leading to a potentiated response to subsequent stress. The implications for understanding the pathoaetiology of mental disorders and the development of new treatments are also considered.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.