The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index; 1 of the 64 sources its claims cite were checked for support.
Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation
Open accessAbstract
Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression and are often associated: but the molecular and clinical mechanisms underlying these abnormalities are still unclear. These findings are particularly enigmatic, especially considering the accepted notion that high levels of cortisol have an anti-inflammatory action, and therefore the coexistence of inflammation and hypercortisolemia in the same diagnostic group appears counter-intuitive. To celebrate the 2015 Anna-Monika Foundation Award to our laboratory, this review will discuss our own 20 years of research on the clinical and molecular evidence underlying the increased inflammation in depression, especially in the context of a hyperactive HPA axis, and discuss its implications for the pathogenesis and treatment of this disorder.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review reflects on 20 years of the author's laboratory research on why a subgroup of depressed patients shows both increased inflammation and HPA-axis abnormalities, proposing glucocorticoid resistance as the linking mechanism. It argues that inflammation in depression is often a "biological scar" of early-life stress and can be used to predict antidepressant non-response.
Key findings
- Increased inflammation and HPA-axis hyperactivity coexist in depression despite cortisol's expected anti-inflammatory action; the author's in vitro work showed IL-1 induces glucocorticoid resistance (impaired GR translocation), while antidepressants reverse it.
- In the GENDEP sample, depressed patients showed increased mRNA of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, MIF) and reduced IL-4, together with reduced GR mRNA and increased FKBP5 — a molecular signature of GR resistance.
- In depressed patients with coronary heart disease, higher IL-6 mRNA and CRP and reduced GR mRNA were found, but associated with HPA-axis hypoactivity rather than hyperactivity.
- Baseline mRNA levels of IL-1, MIF and TNF-alpha predicted roughly half the variance in antidepressant response; in a replication using absolute mRNA values, cut-offs predicted non-response with positive predictive values and specificity of 100%.
- Early-life adversity (childhood maltreatment, and prenatal maternal depression in the South London Child Development Cohort) was associated with raised inflammation markers (CRP, white cell counts, fibrinogen); a randomized controlled trial found prophylactic EPA/DHA prevented or delayed interferon-alpha-induced depression.
Methods
- Design: narrative, self-referential review of the author's own 20 years of research (1991–2017), framed around the 2015 Anna-Monika Foundation Award.
- Evidence base: in vitro models (mouse fibroblasts, human peripheral blood mononuclear cells, human neurons/hippocampal progenitor cells), animal studies, and clinical cohorts including GENDEP, the Dunedin study, and the South London Child Development Cohort, plus an RCT of omega-3 fatty acids.
- Analysis: descriptive synthesis of findings across these studies; no systematic search or meta-analysis is described.
Limitations
- Stated: the review is explicitly self-referential ("the narrative and the citations are self-referential"), and the author lists outstanding unanswered questions, including the epigenetic mechanisms linking early-life events to long-term inflammation, how anti-inflammatories help depression, and whether normalising GR function is helpful for patients.
- Evident from the text: as a single-laboratory narrative review it is not a systematic or exhaustive synthesis, and several cited findings (e.g., the 100% predictive values, preliminary genetic and in utero evidence) are described by the author as preliminary or requiring replication.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
43 Not checked yet · 6 Own interpretation · 1 Partly supported · accuracy not yet measured
In the paper
“these same subjects have glucocorticoid resistance, as shown by a reduced in vitro ability of their peripheral blood mononuclear cells to respond to dexamethasone and cortisol during an immune stimulus (Carvalho et al., 2009).”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Carvalho et al., 2009
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Patients with the highest IL-6 levels are also the least likely to respond to antidepressants (Carvalho et al., 2013).”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Carvalho et al., 2013 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In 2008 we described increased plasma cortisol levels and increased inflammation (plasma IL-6) in the same depressed individuals, a group of severely depressed inpatients with treatment-resistant depression (Carvalho et al., 2008)”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Carvalho et al., 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“we showed that these same patients also have molecular evidence of GR resistance as shown by a reduced expression of GR mRNA together with an increased expression of the GR chaperone protein, FKBP5 (Cattaneo et al., 2013).”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Cattaneo et al., 2013 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“we replicated the increased inflammation in depression as shown by increased mRNA expression of proinflammatory cytokines (IL-1, IL-6, TNF-alpha and macrophage inhibiting factor, MIF) together with a reduced expression of the anti-inflammatory cytokines, IL-4”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Cattaneo et al., 2013 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“we were able to demonstrate that p-glycoprotein regulates the effects of antidepressants on GR expression (Yau et al., 2007)”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Yau et al., 2007 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In two studies in healthy volunteers, we were also able to confirm that antidepressants reverse GR resistance, that is, increase GR function as measured by the HPA axis negative feedback (Pariante et al., 2004a) and the effects of cortisol on the EEG (Pariante et al., 2012).”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Pariante et al., 2004a
- Not checked yetcites Pariante et al., 2012 source
plaindirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“We also showed that the detrimental effects of these inflammatory stimuli can be reversed by antidepressant treatments as diverse as inhibitors of the kynurenine pathways, antioxidants and mitochondrial modulators, and omega-3 polyunsaturated fatty acids”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“an effect that is mediated by an increased production of neurotoxic tryptophan metabolites as well as an increased oxidative stress”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“we indeed demonstrated that antidepressants not only increase neurogenesis, but do so by activating a downstream cascade of second messenger mechanisms that requires the GR (Anacker et al., 2011).”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
- Not checked yetcites Anacker et al., 2011 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 19
- Probably not a substantial claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we found that two proinflammatory cytokines, IL-1 and interferon-alpha, reduce human neurogenesis and human neuronal survival”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
- Not checked yetcites Alboni et al., 2013
- Not checked yetcites Horowitz et al., 2014
- Partly supportedcites Zunszain et al., 2012 sourceExperimental — accuracy not yet measured
The Results section ('IL-1b Decreases Neuronal Differentiation of Human Hippocampal Progenitor Cells'; page not available) reports that IL-1β reduced neuroblasts and mature neurons in human hippocampal cell cultures, supporting reduced neurogenesis. Our copy does not report an experiment showing that interferon-alpha reduces human neurogenesis or that either cytokine reduces human neuronal survival; the interferon-alpha mention found is in a reference title. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we demonstrated that the effects of antidepressants potentiating GR translocation and function is not only directly mediated through steroid-independent activation of the GR, but also indirectly by inhibition of the pglycoprotein transporter that expels cortisol from cells (and, in vivo, from the brain).”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Pariante et al., 2001
- Not checked yetcites Pariante et al., 2003a
- Not checked yetcites Pariante et al., 2003b
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“we also demonstrated that antidepressants in vitro increase GR activation and function, that is, reverse glucocorticoid resistance, thus confirming the crucial role of the GR as a target of both depressogenic (inflammation) and therapeutic (antidepressants) stimuli (Pariante et al., 1997).”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Pariante et al., 1997 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“these effects are common to all tested antidepressants and are present not only in mouse fibroblasts but also in rat neurons”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Pariante et al., 2001
- Not checked yetcites Pariante et al., 2003a
- Not checked yetcites Pariante et al., 2003b
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“we found that incubating L929 mouse fibroblasts cells with the pro-inflammatory cytokine interleukin (IL)-1 leads to glucocorticoid resistance, i.e., to an impairment of GR activation and translocation from the cytoplasm to the nucleus, resulting in reduced expression of GR-stimulated genes (Pariante et al., 1999).”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Pariante et al., 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“but not, however, that pglycoprotein or indeed antidepressants regulate cortisol levels in the brain (Mason et al., 2008(Mason et al., , 2011)).”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Mason et al., 2008
- Not checked yetcites Mason et al., 2011
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“depressed patients with coronary heart disease have higher inflammation (higher IL-6 mRNA and higher levels of c-reactive protein (CRP), an acute phase response protein produced by the liver in response to IL-6) together with a reduced expression of GR mRNA”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Nikkheslat et al., 2015
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“antidepressants increase neurogenesis via a GR-dependent mechanism that requires protein kinase A (PKA) signalling and upregulation of genes such as p11 and the cyclin-dependent kinase-2 (CDK2) inhibitors, p27and p57 (Anacker et al., 2011)”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
- Not checked yetcites Anacker et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“both antidepressants and cortisol require the GR to exert their effects on neurogenesis: but with antidepressants activating the GR in order to increase neurogenesis, while cortisol activating the GR in order to decrease neurogenesis.”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
- Not checked yetcites Anacker et al., 2011 source
- Not checked yetcites Anacker et al., 2013a
- Not checked yetcites Anacker et al., 2013b
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we were able to replicate both the antidepressant-induced upregulation of p11 and the cortisol-induced upregulation of SGK1 in the blood (mRNA) of depressed patients, and the cortisolinduced downregulation of TGFβ-SMAD2/3 and Hedgehog signalling in the hippocampus of adult rats exposed to prenatal stress (Anacker et al., 2013a(Anacker et al., , 2013b)).”
§ ANNA-MONIKA > 4. And from humans to cells
What the sources say
- Not checked yetcites Anacker et al., 2013a
- Not checked yetcites Anacker et al., 2013b
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“we showed that this increased inflammation is present not only in subjects who are depressed and have a history of childhood maltreatment but also in those who have experienced maltreatment but are not depressed (Danese et al., 2008)”
§ ANNA-MONIKA > 5. Why are some depressed patients inflamed?
What the sources say
- Not checked yetcites Danese et al., 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this second cohort, we have confirmed and extended the predictive ability of IL-1 and MIF, and have identified cut-off values for the absolute mRNA measures that accurately predict response probability at an individual level, with positive predictive values and specificity for nonresponders of 100% (Cattaneo et al., 2016).”
§ ANNA-MONIKA > 6. Are these findings clinically relevant?
What the sources say
- Not checked yetcites Cattaneo et al., 2016
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Together, the levels of these three cytokines predict approximately half of the variance in antidepressant response, although IL-1 and MIF explain most of the variance.”
§ ANNA-MONIKA > 6. Are these findings clinically relevant?
What the sources say
- Not checked yetcites Cattaneo et al., 2013 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“in depression, a dysfunction of the GR leads to an impaired HPA axis negative feedback (a phenomenon called glucocorticoid resistance), which in turn leads to the HPA axis hyperactivity (Pariante and Lightman, 2008;Pariante and Miller, 2001).”
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
What the sources say
- Not checked yetcites Pariante and Lightman, 2008 source
- Not checked yetcites Pariante and Miller, 2001
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both these findings indicate the possible molecular signature underlying GR resistance and increased inflammation in depression: a reduced GR expression (that is, less receptor available) together with a decreased GR responsivity (as FKBP5 binds to the GR and maintains it in an unresponsive state).”
§ ANNA-MONIKA > 3. From cells to humans
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings confirmed the notion that glucocorticoid resistance, cortisol hypersecretion and increased inflammation are indeed coexistent and related biological abnormalities.”
§ ANNA-MONIKA > 3. From cells to humans
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This biological picture, perhaps due to the advanced age of the subjects in questions and thus to the long chronicity of their depression, introduces a different type of GR resistance: an ineffective GR together with lower levels of cortisol (Nikkheslat et al., 2015).”
§ ANNA-MONIKA > 3. From cells to humans
What the sources say
- Not checked yetcites Nikkheslat et al., 2015
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Together, these findings indicate that the increased inflammation is a 'biological scar' of the early exposure to high levels of stress, which originates in childhood and is characterised by abnormalities in both mental and physical health (Baumeister et al., 2016).”
§ ANNA-MONIKA > 5. Why are some depressed patients inflamed?
What the sources say
- Not checked yetcites Baumeister et al., 2016 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“There is consistent evidence from candidate gene studies that genetic variants that increase immune responses are more frequent in patients with depression, or characterise a group of individuals who are at risk of developing a depressive phenotype in the context of an immune challenge (Barnes et al., 2017).”
§ ANNA-MONIKA > 5. Why are some depressed patients inflamed?
What the sources say
- Not checked yetcites Barnes et al., 2017
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The strong impact of the immune system on emotions and behaviour demonstrates that mental health is the health of the whole body.”
§ ANNA-MONIKA > 7. Conclusions
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
The paper relies on this without support.
The molecular and clinical mechanisms underlying the association between increased inflammation and HPA axis hyperactivity in major depression are still unclear.
“the molecular and clinical mechanisms underlying these abnormalities are still unclear.”
The paper relies on this without support.
Not all depressed patients have increased inflammation.
“Not all depressed patients have increased inflammation: so, who are these patients that present with this biological phenotype?”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Abundant evidence supports the role of neuroinflammation and altered immune processes in the aetiopathogeneses of various mental conditions (Mazza, Lucchi, Rossetti, & Clerici, 2020; Pariante, 2017).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Pariante, 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“It is important to take into account that some of these processes participate in disease pathogenesis in a parallel manner, such as via the redox system and through the glutamatergic/GABAergic imbalance (Hardingham & Do, 2016); or the immune system and the stress response (Pariante, 2017).”
From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Pariante, 2017
In the citing paper
“A group of determinants touched upon by several studies included adverse childhood or early life experiences: ex. conflict with parents, early exposure to traumatic life events, bullying and childhood trauma were found to increase the risk of depression (ex. through pathways, such as inflammation, interaction effects, or cognitive biases) [161,182,258,358,362,380].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [182]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ ANNA-MONIKA > 2. Inflammation and the glucocorticoid receptor: love at first sight
“Two subsequent papers demonstrated similar findings in human peripheral blood mononuclear cells (Carvalho et al., 2008(Carvalho et al., , 2010)).”
§ ANNA-MONIKA > References
“Clomipramine in vitro reduces glucocorticoid receptor function in healthy subjects but not in patients with major depression.”
Citations
Cites
The HPA axis in major depression: classical theories and new developments
Pariante, C. M., & Lightman, S. L. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.006 · Cited by 2,009
Self-citationChildhood maltreatment predicts adult inflammation in a life-course study
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610362104 · Cited by 1,264 · cited 1×
“…with Avshalom Caspi and Terrie Moffitt on the Dunedin study, we were the first to demonstrate that young adults with a history of childhood trauma show increased inflammation, as demonstrated by increased CRP, increased white blood cell counts and increased fibrinogen levels (Danese et al., 2007).”
Self-citationDanese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., Poulton, R., & Caspi, A. (2009) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpediatrics.2009.214 · Cited by 1,165
Self-citationGlucocorticoid receptors in major depression: relevance to pathophysiology and treatment
Pariante, C. M., & Miller, A. H. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01088-x · Cited by 1,147
Self-citationBaumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.67 · Cited by 1,084
Self-citationElevated inflammation levels in depressed adults with a history of childhood maltreatment
Danese, A., Moffitt, T. E., Pariante, C. M., Ambler, A., Poulton, R., & Caspi, A. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.4.409 · Cited by 641 · cited 2×
“In subsequent reports, we showed that this increased inflammation is present not only in subjects who are depressed and have a history of childhood maltreatment but also in those who have experienced maltreatment but are not depressed (Danese et al., 2008); moreover, the increased inflammation clusters with metabolic…”
Self-citationCattaneo, A., Gennarelli, M., Uher, R., Breen, G., Farmer, A., Aitchison, K. J., Craig, I. W., Anacker, C., Zunsztain, P. A., McGuffin, P., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.191 · Cited by 436
Self-citationAntidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
Anacker, C., Zunszain, P. A., Cattaneo, A., Carvalho, L. A., Garabedian, M. J., Thuret, S., Price, J., & Pariante, C. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.26 · Cited by 435
Self-citationInterleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis
Zunszain, P. A., Anacker, C., Cattaneo, A., Choudhury, S., Musaelyan, K., Myint, A. M., Thuret, S., Price, J., & Pariante, C. M. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.277 · Cited by 388
Self-citationGlucocorticoid-Related Molecular Signaling Pathways Regulating Hippocampal Neurogenesis
Anacker, C., Cattaneo, A., Luoni, A., Musaelyan, K., Zunszain, P. A., Milanesi, E., Rybka, J., Berry, A., Cirulli, F., Thuret, S., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.253 · Cited by 331
Self-citation
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
“…is a major risk factor for MDD. Chronic stress has reliably been associated with HPA axis abnormalities along with the salient features of inflammation in patients and animal models (Espinosa-Oliva et al., 2011; Farooq et al., 2018; Laugeray et al., 2016; Pariante, 2017; Surget et al., 2011).”
BackgroundInfluentialMicrobiome–host systems interactions: protective effects of propionate upon the blood–brain barrier
Hoyles, L., Snelling, T., Umlai, U.-K., Nicholson, J. K., Carding, S. R., Glen, R. C., & McArthur, S. (2018) · Microbiome · doi:10.1186/s40168-018-0439-y · Cited by 591
“That inflammation contributes to depression has become clearer over recent years [78]; hence, it is conceivable that the anti-inflammatory effects of propionate we describe may underlie at least part of the protective effects of prebiotic treatment, a proposal which, though speculative, is deserving of further study.”
BackgroundMolecular pathways of major depressive disorder converge on the synapse
Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504
“Inflammation Several studies have found that MDD and a dysregulation of the inflammatory process are associated in a bidirectional pathway (“cytokine theory of MDD”) [125].”
BackgroundBiological, Psychological, and Social Determinants of Depression: A Review of Recent Literature
Remes, O., Mendes, J. F., & Templeton, P. (2021) · Brain Sciences · doi:10.3390/brainsci11121633 · Cited by 482
“through pathways, such as inflammation, interaction effects, or cognitive biases) [161,182,258,358, 362,380].”
BackgroundThe HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?
Misiak, B., Łoniewski, I., Marlicz, W., Frydecka, D., Szulc, A., Rudzki, L., & Samochowiec, J. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109951 · Cited by 343
Tian, P., O’Riordan, K. J., Lee, Y. K., Wang, G., Zhao, J., Zhang, H., Cryan, J. F., & Chen, W. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100216 · Cited by 297
“…alteration in glucocorticoid receptor gene expression can lead to glucocorticoid resistance and is also coincident with a high level of inflammation, consistent with previous reports (Cohen et al., 2012; Dendoncker and Libert, 2017; Keller et al., 2017; Pariante, 2017; Pariante and Lightman, 2008).”
Bernarás, E., Jaureguizar, J., & Garaigordobil, M. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00543 · Cited by 334
The self in context: brain systems linking mental and physical health
Koban, L., Gianaros, P. J., Hedy Kober, A., & Wager, T. D. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00446-8 · Cited by 258
Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment
Mazza, M. G., Palladini, M., Poletti, S., & Benedetti, F. (2022) · CNS Drugs · doi:10.1007/s40263-022-00931-3 · Cited by 248
“However, high levels of glucocorticoids may, in the long term, cause resistance to glucocorticoid feedback on the HPA axis, thus allowing pro-inflammatory signaling pathways to avoid normal feedback inhibition [90].”
BackgroundOsborne, S., Biaggi, A., Chua, T.-E., Preez, A. D., Hazelgrove, K. M., Nikkheslat, N., Previti, G., Zunszain, P. A., Conroy, S., & Pariante, C. M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.06.017 · Cited by 221
“Indeed, studies of symptoms of depression in pregnancy have provided some evidence of the same altered inflammation and HPA axis activity found in depression outside of pregnancy (Pariante and Lightman, 2008; Miller and Raison, 2016; Pariante, 2017).”
Self-citationMolecular links between endocrine, nervous and immune system during chronic stress
Zefferino, R., Di Gioia, S., & Conese, M. (2021) · Brain and Behavior · doi:10.1002/brb3.1960 · Cited by 204
“, in depression) cause resistance to glucocorticoid feedback on the HPA axis, and this developed glucocorticoid resistance allows the escape of proinflammatory signaling pathways from normal feedback inhibition (Pariante, 2017).”
BackgroundZhang, Y., Long, Y., Yu, S., Li, D., Yang, M., Guan, Y., Zhang, D., Wan, J., Liu, S., Shi, A., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105376 · Cited by 211
Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review
Lwin, M. N., Serhal, L., Holroyd, C. R., & Edwards, C. J. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00217-4 · Cited by 201
“In RA, inflammatory markers including CRP, ESR and pro-inflammatory cytokines TNF-a , IL-1, Il-6 and IFN-a levels are elevated, and such increased levels of inflammation are regarded as a ‘‘biological scar’’ that increases the risk of depression [69].”
The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder
Woelfer, M., Kasties, V., Kahlfuss, S., & Walter, M. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.034 · Cited by 171
Inflammatory mediators in major depression and bipolar disorder
Poletti, S., Mazza, M. G., & Benedetti, F. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02921-z · Cited by 195
Qin, Z., Shi, D., Li, W., Cheng, D., Zhang, Y.-D., Zhang, S., Tsoi, B., Zhao, J., Wang, Z., & Zhang, Z. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02744-7 · Cited by 177
Role of inflammation in depression relapse
Liu, C., Zhang, G., Li, B., Li, M., Woelfer, M., Walter, M., & Wang, L. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1475-7 · Cited by 170
Giacobbe, J., Benoiton, B., Zunszain, P., Pariante, C. M., & Borsini, A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00122 · Cited by 159
“Over the last few decades, inflammation has been identified as one of the main pathophysiological mechanisms underlying psychiatric conditions (1, 2).”
BackgroundSelf-citationBottaccioli, A. G., Bottaccioli, F., & Minelli, A. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13728 · Cited by 173
Sadeghi, O., Keshteli, A. H., Afshar, H., Esmaillzadeh, A., & Adibi, P. (2021) · Nutritional Neuroscience · doi:10.1080/1028415x.2019.1620425 · Cited by 157
“Mediterranean diet has been associated with lower levels of circulating inflammation, which is strongly linked with psychological disorders [61,62].”
BackgroundMolecular Mechanisms of Neurogenic Inflammation of the Skin
Marek‐Józefowicz, L., Nedoszytko, B., Grochocka, M., Zmijewski, M. A., Czajkowski, R., Cubała, W. J., & Slominski, A. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055001 · Cited by 164
Physical Exercise and Neuroinflammation in Major Depressive Disorder
Ignácio, Z. M., da Silva, R. S., Plissari, M. E., Quevedo, J., & Réus, G. Z. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01670-1 · Cited by 153
The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects
Marek‐Józefowicz, L., Czajkowski, R., Borkowska, A., Nedoszytko, B., Zmijewski, M. A., Cubała, W. J., & Slominski, A. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020669 · Cited by 166
“Two major types of receptors can help the HPA axis exert its fe dback function: the glucocorticoid (GR) and mineralocorticoid receptor (MR) [102].”
BackgroundThe role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135
“…that clinical depression is a highly heterogeneous disorder with multiple, intertwined aetiologies linked to alterations in brain plasticity and monoamine functions in general, as well as disturbances in the immune system and the HPA axis (Miller & Raison, 2016; Pariante, 2017; Levy et al., 2018).”
BackgroundChildhood trauma in mood disorders: Neurobiological mechanisms and implications for treatment
Jaworska-Andryszewska, P., & RYBAKOWSKI, J. K. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.10.004 · Cited by 133
Molecular aspects of depression: A review from neurobiology to treatment
Boas, G. R. V., de Lacerda, R. B., Paes, M. M., Gubert, P., Almeida, W. L. D. C., Rescia, V. C., Galdino, P. M., de Carvalho, A. A. V., & Oesterreich, S. A. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.02.024 · Cited by 140
Song, Q., Fan, C., Wang, P., Li, Y., Yang, M., & Yu, S. Y. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1377-0 · Cited by 126
Childhood trauma, HPA axis activity and antidepressant response in patients with depression
Nikkheslat, N., McLaughlin, A. P., Hastings, C., Zajkowska, Z., Nettis, M. A., Mariani, N., Enache, D., Lombardo, G., Pointon, L., Cowen, P. J., et al. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.11.024 · Cited by 124
“Indeed, attenuated glucocorticoid responsiveness, so called glucocorticoid resistance, has been consistently observed in MDD patients presenting coexistence of hypercortisolemia and inflammation (Pariante, 2017, Perrin et al., 2019, Stewart et al., 2009).”
BackgroundInfluentialSelf-citationBiomarkers of Pathological Dissociation: A Systematic Review
Roydeva, M. I., & Reinders, A. A. T. S. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.019 · Cited by 116
Cattaneo, A., Ferrari, C., Turner, L., Mariani, N., Enache, D., Hastings, C. N. M., Kose, M., Lombardo, G., McLaughlin, A. P., Nettis, M. A., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00874-7 · Cited by 120
Self-citationGustafsson, H., Sullivan, E. L., Nousen, E. K., Sullivan, C. A., Huang, E., Rincon, M. P., Nigg, J. T., & Loftis, J. M. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.011 · Cited by 118
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106
“We suggest that a treatment approach should consider the inflammatory history of the individual (with the standard treatment protocol available), given that pre-existent dysregulated inflammatory activity can modulate treatment outcomes (Uher et al., 2014; Lasselin et al., 2016b; Carvalho et al., 2012; Pariante, 2017).”
Kremer, M., Yalçın, İ., Goumon, Y., Wurtz, X., Nexon, L., Daniel, D., Megat, S., Ceredig, R. A., Ernst, C., Turecki, G., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1004-18.2018 · Cited by 104
The role of yoga in inflammatory markers
Estevao, C. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100421 · Cited by 121
“However, the study found no significant effects in TNF- α or cortisol levels, which are, interestingly, regulated independently of IL-6 (Pariante, 2017; Del Giudice and Gangestad, 2018).”
BackgroundChemokine alterations in bipolar disorder: A systematic review and meta-analysis
Misiak, B., Bartoli, F., Carrà, G., Małecka, M., Samochowiec, J., Jarosz, K., Banik, A., & Stańczykiewicz, B. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.04.013 · Cited by 102
“Available evidence indicates that treatment-resistance and a history of childhood trauma are well-known correlates of subclinical inflammation in depression and thus they might account for variability of cytokine levels in this group of patients (Pariante, 2017).”
Effects of SSRIs on Peripheral Inflammatory Cytokines in Patients with Generalized Anxiety Disorder
Hou, R., Ye, G., Liu, Y., Chen, X., Pan, M., Zhu, F., Fu, J., Fu, T., Liu, Q., Gao, Z., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.06.001 · Cited by 97
Fan, C., Song, Q., Wang, P., Li, Y., Yang, M., & Yu, S. Y. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00516 · Cited by 100
“…increased inflammation, previous study reported that the increased inflammation is mainly present in a subgroup of depressed patients who exposure to stress early in childhood or even in utero, and these depressed patients is less likely to respond to conventional antidepressants (Pariante, 2017).”
BackgroundPerrin, A. J., Horowitz, M. A., Roelofs, J., Zunszain, P. A., & Pariante, C. M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00423 · Cited by 98
“The conflicting nature of the primary literature, combined with a consensus in the field that such a positive association indeed exists (11, 57), lead us to conduct the systematic review and meta-analytic work described above.”
BackgroundMethodResultInfluentialSelf-citationNeuroinflammation in Post-Traumatic Stress Disorder
Lee, D.-H., Lee, J.-Y., Hong, D.-Y., Lee, E.-C., Park, S.-W., Lee, M. R., & Oh, J. S. (2022) · Biomedicines · doi:10.3390/biomedicines10050953 · Cited by 102
Short-term PM2.5 exposure and emergency hospital admissions for mental disease
Lee, S., Lee, W., Kim, D., Kim, E., Myung, W., Kim, S., & Kim, H. (2019) · Environmental Research · doi:10.1016/j.envres.2019.01.036 · Cited by 96
Tayab, M. A., Islam, M. N., Chowdhury, K. A. A., & Tasnim, F. M. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112668 · Cited by 100
Treatment-Resistant Depression Revisited: A Glimmer of Hope
Halaris, A. E., Sohl, E., & Whitham, E. A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020155 · Cited by 101
“This feedback loop increasingly fails due to a reduction in both the number of expressed GRs and GR desensitization [32].”
BackgroundWang, X., Li, Y., Wu, L., Xiao, S., Ji, Y., Tan, Y., Jiang, C., & Zhang, G. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111065 · Cited by 95
Stress and coping in women with breast cancer:unravelling the mechanisms to improve resilience
Borgi, M., Collacchi, B., Ortona, E., & Cirulli, F. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.011 · Cited by 90
Misiak, B., Wójta-Kempa, M., Samochowiec, J., Schiweck, C., Aichholzer, M., Reif, A., Samochowiec, A., & Stańczykiewicz, B. (2022) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2022.110581 · Cited by 93
“Indeed, this observation has been made in patients with depression (Pariante, 2017).”
Oleoylethanolamide, Neuroinflammation, and Alcohol Abuse
Orío, L., Alén, F., Pavón, F. J., Serrano, A., & García‐Bueno, B. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00490 · Cited by 91
“…all these alterations can even affect other multifaceted processes, such as monoaminergic and glutamatergic neurotransmission (Ogyu et al., 2018), neuroendocrine responses (Pariante, 2017), cognition (Skaper et al., 2014), and ultimately behavior (Dantzer et al., 2008; McCusker and Kelley, 2013).”
BackgroundIob, E., Lacey, R. E., & Steptoe, A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.12.019 · Cited by 95
“Please cite this article as: Eleonora Iob, Rebecca Lacey and Andrew Steptoe, Brain, Behavior, and Immunity, https://doi.org/10.1016/j.bbi.2019.12.019 be concurrent in the context of chronic stress (Pariante, 2017).”
InfluentialDionysopoulou, S., Charmandari, E., Bargiota, Α., Vlahos, N., Mastorakos, G. P., & Valsamakis, G. (2021) · Nutrients · doi:10.3390/nu13020498 · Cited by 91
Evolution of a maternal immune activation (mIA) model in rats: Early developmental effects
Murray, K. N., Edye, M. E., Manca, M., Vernon, A. C., Oladipo, J. M., Fasolino, V., Harte, M., Mason, V., Grayson, B., McHugh, P., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.09.005 · Cited by 91
“In the depression field there is growing evidence to support the hypothesis that non-responders to standard medication have a pro-inflammatory profile (see (Pariante, 2017) for a recent update).”
Athira, K. V., Madhana, R. M., Indu Chandran, J. S., Lahkar, M., Sinha, S., & Naidu, V. G. M. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.009 · Cited by 85
“Based on the exaggerated immune response in the presence of HPA axis dysregulation induced by CORT, it may be assumed that the underlying cause to be GC resistance [48].”
BackgroundGeng, J., Liu, J., Yuan, X., Liu, W., & Guo, W. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114688 · Cited by 82
Zhan, Y., Zhou, Y., Zheng, W., Liu, W., Wang, C., Lan, X., Deng, X., Xu, Y., Zhang, B., & Ning, Y. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00933-z · Cited by 81
Rothe, N., Steffen, J., Penz, M. S., Kirschbaum, C., & Walther, A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.024 · Cited by 90
Faraji, N., Payami, B., Ebadpour, N., & Gorji, A. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105990 · Cited by 89
Gulyaeva, N. V. (2019) · Biochemistry (Moscow) · doi:10.1134/s0006297919110087 · Cited by 81
“Considering the accepted notion that high levels of cortisol have anti inflammatory properties, this associa tion is particularly enigmatic [38] (Fig.”
BackgroundLipidomics in Major Depressive Disorder
Walther, A., Cannistraci, C. V., Simons, K., Durán, C., Gerl, M. J., Wehrli, S., & Kirschbaum, C. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00459 · Cited by 77
“Although advancements in elucidating the pathophysiology of MDD have been achieved (11), one needs to acknowledge that the reductionist single biomarker approach employed during the last decades has been a failure (12).”
BackgroundChanges in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes
Xu, W., Yao, X., Zhao, F., Zhao, H., Cheng, Z., Yang, W., Cui, R., Xu, S., & Li, B. (2020) · Neural Plasticity · doi:10.1155/2020/8861903 · Cited by 75
Caraci, F., Calabrese, F., Molteni, R., Bartova, L., Dold, M., Leggio, G. M., Fabbri, C., Mendlewicz, J., Racagni, G., Kasper, S. F., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014977 · Cited by 76
Cognitive dysfunction in major depression: From assessment to novel therapies
Atique-Ur-Rehman, H., & Neill, J. C. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.013 · Cited by 72
“variants include G-174C, Banl, and COX2 rs4648308 polymorphisms in the IL-6, cytosolic phospholipase A2 and COX-2 genes respectively (Pariante, 2017).”
BackgroundThe Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases
Zhao, S., Li, X., Wang, J., & Wang, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.657478 · Cited by 72
“Increased inflammation is involved in the progression of depression, and the activation of NLRP3 inflammasome in microglia is an important feature of CNS inflammation under chronic stress (Pan et al., 2014; Pariante, 2017).”
BackgroundConnecting Dots between Mitochondrial Dysfunction and Depression
Khan, M., Baussan, Y., & Hébert-Chatelain, É. (2023) · Biomolecules · doi:10.3390/biom13040695 · Cited by 77
Caruso, G., Fresta, C. G., Grasso, M., Santangelo, R., Lazzarino, G., Lunte, S. M., & Caraci, F. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190712091515 · Cited by 74
The Role of Anxious Distress in Immune Dysregulation in Patients with Major Depressive Disorder
Gaspersz, R., Lamers, F., Wittenberg, G., Beekman, A. T. F., van Hemert, A. M., Schoevers, R. A., & Penninx, B. W. J. H. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0016-3 · Cited by 71
Steroid secretion in healthy aging
Fiacco, S., Walther, A., & Ehlert, U. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.09.035 · Cited by 71
Maternal depression and inflammation during pregnancy
Lahti‐Pulkkinen, M., Girchenko, P. V., Robinson, R., Lehto, S. M., Toffol, E., Heinonen, K., Reynolds, R. M., Kajantie, E., Laivuori, H. M., Villa, P., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291719001909 · Cited by 69
Towards Neuroecosociality: Mental Health in Adversity
Rose, N., Birk, R. H., & Manning, N. (2021) · Theory Culture & Society · doi:10.1177/0263276420981614 · Cited by 77
“Research does suggest pathways that do not respect the boundaries of skull and skin, and demonstrates the constitutive embeddedness of neural processes in their material milieu (Alam et al., 2017; Borsini et al., 2015; Pariante, 2017).”
Microglia and HPA axis in depression: An overview of participation and relationship
Pereira, G. C., Piton, E., dos Santos, B. M., Ramanzini, L. G., Camargo, L. F. M., da Silva, R. M., & Bochi, G. V. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1939154 · Cited by 72
Ghazizadeh‐Hashemi, M., Ghajar, A., Shalbafan, M., Ghazizadeh‐Hashemi, F., Afarideh, M., Malekpour, F., Ghaleiha, A., Ardebili, M. E., & Akhondzadeh, S. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.02.057 · Cited by 67
Gustafsson, H., Sullivan, E. L., Battison, E., Holton, K. F., Graham, A. M., Karalunas, S. L., Fair, D. A., Loftis, J. M., & Nigg, J. T. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.019 · Cited by 66
“, 2019), though it operates in conjunction with associated systems, including glucocorticoid function (Osborne et al., 2018; Pariante, 2017).”
BackgroundAmasi-Hartoonian, N., Sforzini, L., Cattaneo, A., & Pariante, C. M. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100356 · Cited by 77
Self-citationUnderstanding long COVID: nosology, social attitudes and stigma
Byrne, E. A. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.09.012 · Cited by 61
Brain-immune crosstalk in the treatment of major depressive disorder
Branchi, I., Poggini, S., Capuron, L., Benedetti, F., Poletti, S., Tamouza, R., Drexhage, H. A., Penninx, B. W. J. H., & Pariante, C. M. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.11.016 · Cited by 66
Self-citationNeutrophil/Lymphocyte, Platelet/Lymphocyte, and Monocyte/Lymphocyte Ratios in Mood Disorders
Marazziti, D., Torrigiani, S., Carbone, M. G., Mucci, F., Flamini, W., Ivaldi, T., & Dell'Osso, L. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867328666210922160116 · Cited by 61
Oudin, A., Åström, D. O., Asplund, P., Steingrímsson, S., Szabó, Z., & Carlsen, H. K. (2018) · Environmental Health · doi:10.1186/s12940-017-0348-8 · Cited by 65
“These recent studies suggest that air pollution exposure had acute effects while both chronic activation and inappropriate regulation of the hypothalamicpituitary-adrenal axis and inflammation were associated with worsening in depressive symptoms [36].”
BackgroundYu, H., Zhang, F., & Guan, X. (2019) · Phytotherapy Research · doi:10.1002/ptr.6340 · Cited by 59
“This evidence raises the possibility that inhibition of inflammation might be a potential therapeutic strategy for depression (Malek et al., 2015; Pariante, 2017).”
BackgroundHorowitz, M. A., Cattaneo, A., Cattane, N., Lopizzo, N., Tojo, L. M., Bakunina, N., Musaelyan, K., Borsini, A., Zunszain, P. A., & Pariante, C. M. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.012 · Cited by 61
“…in depression: raised cortisol levels and evidence of glucocorticoid resistance have been identified in depressed patients (Juruena et al., 2006; Pariante, 2017, 2009), including in metaanalysis (Stetler and Miller, 2011), as are increased levels of pro-inflammatory cytokines (Dantzer, 2018;…”
BackgroundSelf-citationLu, S.-Y., Peng, X., Dong, J.-R., Yan, H., Kong, Q., Shi, Q., Li, D., Zhou, L. M., Li, Z., & Qiu, M. (2019) · Fitoterapia · doi:10.1016/j.fitote.2019.01.013 · Cited by 58
Can epigenetics shine a light on the biological pathways underlying major mental disorders?
Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y., & Forti, M. D. (2022) · Psychological Medicine · doi:10.1017/s0033291721005559 · Cited by 60
“It is important to take into account that some of these processes participate in disease pathogenesis in a parallel manner, such as via the redox system and through the glutamatergic/GABAergic imbalance (Hardingham & Do, 2016); or the immune system and the stress response (Pariante, 2017).”
BackgroundCordeiro, R. C., Filho, A. J. M. C., Gomes, N. S., Tomaz, V. D. S., Medeiros, C. D., Queiroz, A. I. D. G., Maes, M. H. J., Macêdo, D. S., & Carvalho, A. F. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00125 · Cited by 55
“Peripheral immune activation and inflammation may contribute to the emergence of depression through several mechanisms including the activation of the kynurenine pathway (10), alterations in neuronal plasticity (11), microglial activation (12), and neuroendocrine effects (13).”
BackgroundBrunoni, A. R., Padberg, F., Vieira, É. L. M., Teixeira, A. L., Carvalho, A. F., Lotufo, P. A., Gattaz, W. F., & Benseñor, I. M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.06.003 · Cited by 59
“Although distinct, these theories are complementary since heightened stress response, observed in MDD, leads to increased activity of the hypothalamic-pituitary-adrenal axis and higher cortisol levels (Gold, 2015; Pariante, 2017) which could lead to an upregulation of pro-inflammatory cytokines accompanied by a downre…”
Disease- and treatment-associated acquired glucocorticoid resistance
Wilkinson, L., Verhoog, N. J. D., & Louw, A. (2018) · Endocrine Connections · doi:10.1530/ec-18-0421 · Cited by 54
Murri, M. B., Folesani, F., Zerbinati, L., Nanni, M. G., Ounalli, H., Caruso, R., & Grassi, L. G. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17155545 · Cited by 58
Ellul, P., Mariotti‐Ferrandiz, E., Leboyer, M., & Klatzmann, D. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00167 · Cited by 55
de Punder, K., Entringer, S., Heim, C. C., Deuter, C. E., Otte, C., Wingenfeld, K., & Kuehl, L. K. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00610 · Cited by 52
“Altogether, the data presented here support the hypothesis that ACEmight be a risk factor for developing aMDD later in life, and that this risk is partly mediated by increases in activation of pro-inflammatory pathways (19).”
BackgroundResultPalma‐Gudiel, H., Córdova‐Palomera, A., Tornador, C., Falcón, C., Bargalló, N., Deco, G., & Fañanás, L. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.03.015 · Cited by 50
Advances in the mechanisms of polysaccharides in alleviating depression and its complications
Guo, Y., Chen, X., Gong, P., Li, Z., Wu, Y., Zhang, J., Wang, J., Yao, W., Yang, W., & Chen, F. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154566 · Cited by 55
Chen, T., Liu, S., Zheng, M., Li, Y., & He, L. (2020) · Phytotherapy Research · doi:10.1002/ptr.6846 · Cited by 51
“A battery of evidence indicated that immunological dysregulation contributed to the onset of depression (Pariante, 2017).”
BackgroundNuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis
Ó’Léime, C. S., Cryan, J. F., & Nolan, Y. M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.07.153 · Cited by 53
Dattilo, V., Amato, R., Perrotti, N., & Gennarelli, M. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00826 · Cited by 49
“Vice versa, the depression resulting from post-traumatic stress such as childhood and adolescent maltreatments is associated with a strong inflammatory component in the presence of decreased levels of SGK1, accompanied by reduced hippocampal neurogenesis (Pariante, 2017).”
BackgroundWu, Q., Miao, X.-Y., Cao, Y.-Y., Chi, A.-P., & Xiao, T. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1243213 · Cited by 46
“Meta-analysis has indicated that an overactive hypothalamic–pituitary–adrenal axis is connected to the development of depression (64), and it can also influence the cardiovascular system of humans by modulating autonomic nerves (6).”
BackgroundLow glucocorticoids in stress-related disorders: the role of inflammation
Sarapultsev, A., Sarapultsev, P., Dremencov, E., Komelkova, M. V., Tseilikman, O. B., & Цейликман, В. Э. (2020) · Stress · doi:10.1080/10253890.2020.1766020 · Cited by 49
Mental health and immunity (Review)
Vasile, C. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9341 · Cited by 58
“The inflammatory immune response to stress, together with the link between stress and depression, shows that there is a correlation between inflam‐ mation and depression (15,16).”
BackgroundBrain–heart communication in health and diseases
Liu, W., Zhang, X., Wu, Z., Huang, K., Yang, C., & Yang, L. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.02.012 · Cited by 49
Persistence of learning-induced synapses depends on neurotrophic priming of glucocorticoid receptors
Arango-Lievano, M., Borie, A. M., Dromard, Y., Murat, M., Desarménien, M. G., Garabedian, M. J., & Jeanneteau, F. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903203116 · Cited by 45
“For example, glucocorticoid receptor insufficiency is associated with a state of low BDNF levels in diseases presenting an activated inflammatory system that is relevant for patients with major depression, schizophrenia, glucocorticoid resistance syndrome, Alzheimer’s disease (57-60).”
BackgroundSong, L., Wu, X., Wang, J., Guan, Y., Zhang, Y., Gong, M., Wang, Y., & Li, B. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.09.002 · Cited by 46
Clerici, L., Bottari, D., & Bottari, B. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00619-2 · Cited by 54
Cai, Z., Ye, T., Xu, X., Gao, M., Zhang, Y.-R., Wang, D., Gu, Y., Zhu, H., Tong, L., Lu, J., et al. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109931 · Cited by 43
Targeting PDK2 rescues stress-induced impaired brain energy metabolism
Wang, C., Cui, C., Xu, P., Zhu, L., Xue, H., Chen, B., & Jiang, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02098-9 · Cited by 46
Vagus nerve stimulation and Neurotrophins: a biological psychiatric perspective
Rosso, P., Iannitelli, A., Pacitti, F., Quartini, A., Fico, E., Fiore, M., Greco, A., Ralli, M., & Tirassa, P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.034 · Cited by 45
Metadata
- Authors
- Pariante, C. M.
- Affiliations
- King's College London (GB)
- Corresponding author
- Pariante, Carmine M.
- ORCID
- Pariante, Carmine M.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 27
- Issue
- 6
- Pages
- 554-559
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2611710834
- Cited by
- 382
- References
- 50
- Citations by year
- 2026: 29 · 2025: 31 · 2024: 56 · 2023: 32 · 2022: 40 · 2021: 44 · 2020: 59 · 2019: 43 · 2018: 39 · 2017: 9
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- European Neuropsychopharmacology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by-nc-nd)
- Funders
- mmunopsychiatry (MR/L014815/1)
- Medical Research Council (MR/J002739/1)
- National Institute for Health Research Mental Health Biomedical Research Centre
- Maudsley NHS Foundation Trust
- King׳s College London
- Wellcome Trust Consortium
- NARSAD
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- major depressive disorder, inflammation, glucocorticoid resistance, hypothalamic-pituitary-adrenal axis, hypercortisolism, cortisol, depression pathogenesis, depression treatment
- MeSH terms
- Anti-Inflammatory Agents, Depression, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Inflammation, Metabolism, Inborn Errors, Pituitary-Adrenal System, Receptors, Glucocorticoid, Time Factors, Inflammation Mediators, Biomedical Research
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
