The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index; 3 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
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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.
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Claims the paper makes
41 Not checked yet · 6 Own interpretation · 2 Supported · 1 Partly supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
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
- Supportedcites Cattaneo et al., 2013 source
The Results (‘Biomarkers Differences between Patients at Baseline, and Controls’) report lower GR mRNA and higher FKBP-5 mRNA in depressed GENDEP patients than in controls. The Discussion interprets the combination as evidence suggesting GR resistance. The study measured FKBP-5 mRNA, not protein abundance. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
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.
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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.
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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.
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- 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.
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- 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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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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.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
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
- Supportedcites Danese et al., 2008 source
The Results section, “Which depressed individuals show increased inflammation?”, reports higher inflammatory markers in both the depressed-and-maltreated and maltreated-only groups than in controls. The Conclusions likewise state that maltreatment history conferred elevated inflammation risk even without a current depression diagnosis. (LLM, conf=0.94)
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.
- Supported
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.
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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.
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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
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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
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Items 101–200 of 380
Hair cortisol and depressive symptoms in youth: An investigation of curvilinear relationships
Ford, J. L., Boch, S. J., & Browning, C. R. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104376 · Cited by 41
“However, there is evidence of heterogeneity in the inflammation-depression association, which highlights the need for further mechanistic research to better understand the complexity of psychopathology (Guerry and Hastings, 2011; Heim et al., 2000; Pariante, 2017; Ruttle et al., 2011).”
BackgroundWalther, A., Mackens-Kiani, A., Eder, J., Herbig, M., Herold, C., Kirschbaum, C., Guck, J. R., Wittwer, L. D., Beesdo‐Baum, K., & Kräter, M. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01911-3 · Cited by 42
“The two most consistent and salient physiological abnormalities are a hyperactive hypothalamus-pituitary-adrenal (HPA) axis and chronic low-grade inflammation associated with elevated cortisol and proinflammatory cytokine levels, respectively [3].”
BackgroundStressful life events predict one-year change of leukocyte composition in peripheral blood
Penz, M. S., Kirschbaum, C., Buske-Kirschbaum, A., Wekenborg, M., & Miller, R. E. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.006 · Cited by 41
Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms
Brooks, S., Hileman, S. M., Chantler, P. D., Milde, S. A., Lemaster, K., Frisbee, S. J., Shoemaker, J. K., Jackson, D. N., & Frisbee, J. C. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00647.2017 · Cited by 42
Cai, L., Mu, Y.-R., Liu, M., Tang, W., & Li, R. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2019.106182 · Cited by 39
Huang, C., Yuan, Q., Zhang, L., Wang, L., Cui, S., Zhang, K., & Zhou, X. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.658205 · Cited by 42
“There is a significant correlation between childhood trauma and low cortisol arousal levels (49), resulting in pro-inflammatory state, which plays an important role in the development of emotional disorders in adulthood (50).”
BackgroundMihaylova, L. V., Saracheva, K., Ivanovska, M., Petrova, A., Marchev, A. S., Georgiev, M. I., Murdjeva, M., & Getova, D. P. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.09.065 · Cited by 41
“Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins 1β (IL-1β) and 6 (IL-6) are registered in excess in depressed patients with certain phenotypes (Bortolato et al., 2015; Maes et al., 2012; Pariante, 2017).”
BackgroundGao, L., Yan, M., Zhou, L., Wang, J., Sai, C., Fu, Y., Liu, Y., & Ding, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.767333 · Cited by 39
Correia, A. S., & Vale, N. (2024) · International Journal of Translational Medicine · doi:10.3390/ijtm4010010 · Cited by 43
Depression and worry symptoms predict future executive functioning impairment via inflammation
Zainal, N. H., & Newman, M. G. (2021) · Psychological Medicine · doi:10.1017/s0033291721000398 · Cited by 38
“Specifically, heightened inflammation is considered a ‘physiological scar’ of prior increased mental disorder symptoms due to prolonged HPA dysregulation (e.g. excessive cortisol) (Pariante, 2017).”
BackgroundNeurobiological biomarkers of response to ketamine
Kadriu, B., Ballard, E. D., Henter, I. D., Murata, S., Gerlus, N., & Zarate, C. A. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.05.003 · Cited by 36
“However, prolonged episodes of inflammatory stress promote glucocorticoid resistance (Pariante, 2017), which results in persistent elevations of interleukin-1β (IL-1β) and immune activation (Cohen et al., 2012).”
BackgroundPallier, P. N., Ferrara, M., Romagnolo, F., Ferretti, M. T., Soreq, H., & Cerase, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102353 · Cited by 37
“On the other hand, chronic and sub-chronic stress is believed to influence in the long run the susceptibility to mental and neurological health by activating the hypothalamic-pituitary-adrenal (HPA) axis (Pariante, 2017).”
BackgroundHughes, F. M., Odom, M. R., Cervantes, A., Livingston, A. J., & Purves, J. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032821 · Cited by 33
“While not entirely understood, it appears that this observation is dependent on the changes in the expression and sensitivity of glucocorticoid receptors which short-circuits the negative feedback mechanism [64].”
BackgroundRadkhah, N., Rasouli, A., Majnouni, A., Eskandari, E., & Parastouei, K. (2023) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2023.102469 · Cited by 45
“Noncompliance with the MD is linked to circulatory inflammation, a condition closely tied to mental health disorders (Pariante, 2017).”
BackgroundDrug repurposing may generate novel approaches to treating depression
Ebada, M. E. (2017) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12815 · Cited by 36
“Increased cortisol levels were detected in biological fluids of depressed patients.([17,18]) Mifepristone, glucocorticoid receptor antagonist, has been investigated for its effects on psychiatric disorders including depression.”
BackgroundMidouhas, E., Kokosi, T., & Flouri, E. (2019) · BMC Public Health · doi:10.1186/s12889-019-6733-1 · Cited by 32
The biological underpinnings of perinatal depressive symptoms: A multi-systems approach.
Nazzari, S., Fearon, P. R. M., Rice, F. J., Ciceri, F., Molteni, M., & Frigerio, A. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.05.023 · Cited by 34
“…effects, the stress and inflammatory response systems exhibit significant bidirectional interactions (Kuhlman et al., 2017), with a disruption of these circuits being hypothesized to increase vulnerability to several disorders (Raison and Miller, 2003), including depression (Pariante, 2017).”
Spies, L.-M. L., Verhoog, N. J. D., & Louw, A. (2021) · Cells · doi:10.3390/cells10102529 · Cited by 35
“While GRα expression is extremely diverse in patients suffering from psychological conditions, many display increased activation of inflammatory processes and HPA-axis signaling, resulting in hypercortisolaemia and a decrease in the GRα pool in peripheral tissues [51].”
BackgroundRavi, M., Bernabe, B., & Michopoulos, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.868936 · Cited by 27
“Another mechanism by which chronic stress and/or trauma exposure facilitate increased systemic inflammation is via dysregulation of the neuroendocrine hypothalamic-pituitaryadrenal (HPA) axis [for comprehensive reviews, please see (14, 31, 32)].”
BackgroundIs There an Inflammatory Profile of Perinatal Depression?
McCormack, C. A., Abuaish, S., & Monk, C. E. (2023) · Current Psychiatry Reports · doi:10.1007/s11920-023-01414-y · Cited by 31
“Altered immune activity is a compelling mediator between these factors and may explain consistently observed associations between physical and mental health [5], particularly during the peripartum, which is a period of immune modulation.”
BackgroundRemitted depression and cognition in HIV: The role of cortisol and inflammation
Rubin, L. H., Langenecker, S. A., Phan, K. L., Keating, S. M., Neigh, G. N., Weber, K. M., & Maki, P. M. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104609 · Cited by 31
“Albeit counterintuitive, increased inflammation and cortisol hypersecretion (marker of GC receptor resistance) are seen in the same depressed individuals (Pariante, 2017).”
BackgroundMicrobiome–host systems interactions: Protective effects of propionate upon the blood–brain barrierPreprint
Hoyles, L., Snelling, T., Umlai, U. I., Nicholson, J. K., Carding, S. R., Glen, R. C., & McArthur, S. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/170548 · Cited by 31
Longitudinal associations between glucocorticoid receptor methylation and late-life depression
Kang, H.-J., Bae, K.-Y., Kim, S.-W., Shin, I.-S., Kim, H.-R., Shin, M.-G., Yoon, J.-S., & Kim, J.-M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.02.004 · Cited by 30
Karakuła‐Juchnowicz, H., Gałęcka, M., Róg, J., Bartnicka, A., Łukaszewicz, Z., Krukow, P., Morylowska-Topolska, J., Skonieczna‐Żydecka, K., Krajka, T., Jonak, K., et al. (2018) · Nutrients · doi:10.3390/nu10050548 · Cited by 30
“These findings confirmed the notion that glucocorticoid resistance, cortisol hypersecretion and increased inflammation are indeed coexistent and related biological abnormalities [73].”
BackgroundThe (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets
Sah, A., & Singewald, N. (2025) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2025.108825 · Cited by 39
Santoft, F., Hedman‐Lagerlöf, E., Salomonsson, S., Lindsäter, E., Ljótsson, B., Kecklund, G., Lekander, M., & Andréasson, A. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100045 · Cited by 31
“Support for this notion can be found in studies showing that increased inflammation characterizes a subgroup of depressed patients that do not respond to conventional anti-depressants (Pariante, 2017).”
BackgroundKaltenegger, H. C., Marques, M. D., Becker, L., Rohleder, N., Nowak, D., Wright, B. J., & Weigl, M. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.01.222 · Cited by 43
“The finding of a positive effect of CRP on HCC supports the notion of glucocorticoid resistance, meaning that inflammation leads to an impairment of the negative feedback loop of the HPA-axis, which in turn leads to hypercortisolism (Pariante, 2017).”
InfluentialShoji, H., Maeda, Y., & Miyakawa, T. (2024) · Molecular Brain · doi:10.1186/s13041-024-01146-x · Cited by 38
“Accumulating evidence indicates that increased activity in the immune system and inflammatory processes contribute to the development of depression [138–140] and that anti-inflammatory agents, including glucocorticoids, have antidepressant properties [139, 141].”
BackgroundNowacki, J., Wingenfeld, K., Kaczmarczyk, M., Woo, R.-C., Salchow, P., Abu-Tir, I., Piber, D., Hellmann-Regen, J., & Otte, C. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0789-7 · Cited by 26
Daytime naps and depression risk: A meta-analysis of observational studies
Li, L., Zhang, Q., Zhu, L., Zeng, G., Huang, H., Zhuge, J., Kuang, X., Yang, S., Yang, D., Chen, Z., et al. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.1051128 · Cited by 31
“Besides, increased cortisol levels and hyperactivity of the HPA axis induced by glucocorticoid resistance coexist with inflammation in depression patients (Pariante, 2017).”
BackgroundInflammation as a Neurobiological Mechanism of Cognitive Impairment in Psychological Stress
Şahin, Ş. K., & Aslan, E. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2305101 · Cited by 29
Bhattacharyya, S., Dunlop, B. W., MahmoudianDehkordi, S., Ahmed, A. T., Louie, G., Frye, M. A., Weinshilboum, R. M., Krishnan, R. R., Rush, A. J., Mayberg, H. S., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00926 · Cited by 27
“For MDD, hypercortisolemia is known to be highly state dependent in psychotic or melancholic depressions (Pariante, 2017).”
BackgroundMartínez-Botía, P., Velasco, A., Rolle, V., Jiménez-Trevino, L., De la Fuente-Tomás, L., Bernardo, Á., Arias, T., Muñoz-Turrillas, M. D. C., García-Alvarez, L., González-Blanco, L., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.06.006 · Cited by 27
“The role of inflammation and immunomodulation in different conditions or pathologies, including mood disorders, has raised interest recently ( Pariante, 2017 ).”
BackgroundBottaccioli, A. G., Bologna, M., & Bottaccioli, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073932 · Cited by 30
“The vicious circle between stress, inflammation, and depression, in the last 25 years, has been widely analyzed even in molecular detail [127,128].”
BackgroundSforzini, L., Pariante, C. M., Palacios, J. E., Tylee, A. T., Carvalho, L. A., Viganò, C. A., & Nikkheslat, N. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.07.023 · Cited by 26
Self-citationHow inflammation influences psychiatric disease
Ferat-Osorio, E. A., Maldonado-García, J. L., & Pavón, L. (2024) · World Journal of Psychiatry · doi:10.5498/wjp.v14.i3.342 · Cited by 29
Han, Z., Wang, L., Zhu, H., Tu, Y., He, P., & Li, B. (2024) · Food Research International · doi:10.1016/j.foodres.2024.115191 · Cited by 28
State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders
Mucci, F., Marazziti, D., Vecchia, A. D., Baroni, S., Morana, P., Carpita, B., Mangiapane, P., Morana, F., Morana, B., & Dell’Osso, L. (2020) · Life · doi:10.3390/life10060082 · Cited by 29
New agents and perspectives in the pharmacological treatment of major depressive disorder
Sanches, M., Quevedo, J., & Soares, J. C. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110157 · Cited by 26
“The involvement of dysfunctions in the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of depressive disorders is well-established, with a large amount of evidence demonstrating a direct association between exposure to stressful events, elevated cortisol levels and reduced neurogenesis, decreased synp…”
BackgroundKowalska, K., Krzywoszański, Ł., Droś, J., Pasińska, P., Wilk, A., & Klimkowicz‐Mrowiec, A. (2020) · Biomedicines · doi:10.3390/biomedicines8110509 · Cited by 25
“An inflammatory state can contribute to the development and progression of depression pathology, influencing alterations of the neuroplasticity caused by reduced BDNF expression, activity, and affinity to a receptor [30,34,35].”
BackgroundMoulton, C. D., Malys, M. K., Hopkins, C. W. P., Rokakis, A. S., Young, A. H., & Powell, N. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01864-2 · Cited by 25
“For over 25 years, the immune system has been proposed as a potential causal pathway to depression [3].”
Busatto, G. F., de Araújo, A. L., Castaldelli-Maia, J. M., Damiano, R. F., Imamura, M., Guedes, B. F., Pinna, F. R., Sawamura, M. V. Y., Mancini, M. C., da Silva, K. R., et al. (2022) · Psychological Medicine · doi:10.1017/s0033291722001374 · Cited by 25
“…findings suggestive of systemic inflammation were previously reported in association with symptoms of PTSD (Sankowski, Mader, & Valdés-Ferrer, 2015), mood disorders (Pariante, 2017), anxiety disorders (Michopoulos, Powers, Gillespie, Ressler, & Jovanovic, 2017), and ME/CFS (Montoya et al., 2017).”
Depression precedes, but does not follow, gestational diabetes
Clark, C. E., Rasgon, N., Reed, D. E., & Robakis, T. K. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12998 · Cited by 24
“This type of mechanism has a good deal of documented evidence for its contribution to the diabetes-depression association in the nongravid population (46).”
BackgroundAlessi, M. G., & Bennett, J. M. (2020) · Journal of Evaluation in Clinical Practice · doi:10.1111/jep.13386 · Cited by 29
Thiele, S., Sörensen, A., Weis, J., Braun, F., Meyer, P. T., Coenen, V. A., & Döbrössy, M. D. (2020) · Stereotactic and Functional Neurosurgery · doi:10.1159/000504860 · Cited by 24
Blood-brain barrier biomarkers
Zapata-Acevedo, J. F., Mantilla-Galindo, A., Vargas-Sánchez, K., & González-Reyes, R. E. (2024) · Advances in clinical chemistry · doi:10.1016/bs.acc.2024.04.004 · Cited by 23
Manoliu, A., Bosch, O. G., Brakowski, J., Brühl, A. B., & Seifritz, E. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.022 · Cited by 25
Yi, Y., Liu, G., Li, Y., Wang, C., Zhang, B., Lou, H., & Yu, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910259 · Cited by 23
“Previous studies have shown that neuroinflammation plays a considerable role in the promotion of depression [5], associated with the homeostasis disequilibrium of glutamatergic neurotransmission [6,7], and the dysfunction of the hypothalamus–pituitary–adrenal (HPA) axis [8,9].”
BackgroundEndoplasmic reticulum stress and unfolded protein response in immune cell function
Matsushima, G., Yanase, Y., Nakagawa, T., Goda, M., Ozawa, K., & Hosoi, T. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1694102 · Cited by 25
A common clinical conundrum: Antidepressant treatment of depression in pregnant women
Mesches, G. A., Wisner, K. L., & Betcher, H. K. (2020) · Seminars in Perinatology · doi:10.1016/j.semperi.2020.151229 · Cited by 24
Brunoni, A. R., Salum, G. A., Hoffmann, M. S., Goulart, A. C., Barreto, S. M., Canhada, S., Carvalho, A. F., Koyanagi, A., Cálice-Silva, V., Lotufo, P. A., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.074 · Cited by 22
Wang, J., Xu, S., Chen, X., Wang, L., Li, J., Li, G., & Zhang, B. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104106 · Cited by 22
Nikkheslat, N., Pariante, C. M., & Zunszain, P. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00003-9 · Cited by 23
Self-citationNikkheslat, N., Zajkowska, Z., Legido‐Quigley, C., Xu, J., Manfro, P. H., Souza, L., Pereira, R. B., Rohrsetzer, F., Piccin, J., Viduani, A. C., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.11.020 · Cited by 21
Lim, D. W., Park, J., Han, D., Lee, J., Kim, Y. T., & Lee, C.-H. (2020) · Nutrients · doi:10.3390/nu12123809 · Cited by 21
“Although the pathogenesis of depression remains unclear, numerous studies have reported the importance of neuroinflammation in the development of depression [3,4].”
BackgroundNeurobiological Mechanisms Of Depression Following Traumatic Brain Injury
Jahan, A. B., & Tanev, K. S. (2022) · Brain Injury · doi:10.1080/02699052.2022.2145362 · Cited by 22
“Increased pro-inflammatory cytokine production can stimulate the release of cortisol for prolonged periods of time (58).”
BackgroundIacono, L. L., Bussone, S., Andolina, D., Tambelli, R., Troisi, A., & Carola, V. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.07.034 · Cited by 21
The antidepressant effect of testosterone: An effect of neuroplasticity?
Walther, A., Wasielewska, J. M., & Leiter, O. (2019) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2019.05.004 · Cited by 20
Muhsin, H. A., Steingrímsson, S., Oudin, A., Åström, D. O., & Carlsen, H. K. (2021) · Environmental Research · doi:10.1016/j.envres.2021.112001 · Cited by 20
Elbakary, N., Al‐Khuzaei, N., Hussain, T. A., Karawia, A., Smida, M., Abu-Rahma, N., Akel, F., Mahmoud, S. E., Currie, J., Khoodoruth, M. A. S., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119545 · Cited by 21
Higher Concentration of Adrenocorticotropic Hormone Predicts Post-Stroke Depression
Wang, Y., Wang, H., Sun, W., Miao, J., Liang, W., Qiu, X., Lan, Y., Pan, C., Li, G., Zhao, X., et al. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s356361 · Cited by 19
Fat compartments in patients with depression: A meta‐analysis
Cosan, A. S., Schweiger, J. U., Kahl, K. G., Hamann, B., Deuschle, M., Schweiger, U., & Westermair, A. L. (2020) · Brain and Behavior · doi:10.1002/brb3.1912 · Cited by 23
“Concurrently, there is some evidence that increased inflammation is present in a subgroup of depressed patients who were exposed to stress early in childhood or even in utero (Pariante, 2017).”
BackgroundVos, C. F., Birkenhäger, T. K., Nolen, W. A., van den Broek, W. W., Coenen, M. J. H., ter Hark, S. E., Verkes, R., & Janzing, J. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100319 · Cited by 20
“…in 25–50 % of patients with Major Depressive Disorder (MDD), reflected by elevated pro-inflammatory markers, such as C-Reactive Protein (CRP) and the cytokines Tumor Necrosis Factor alpha (TNF-α ) and Interleukin (IL)-6 (Miller, 2020; Dantzer et al., 2008; Miller and Raison, 2016; Pariante, 2017).”
InfluentialBranchi, I., Viglione, A., Vai, B., Cirulli, F., Benedetti, F., & Poggini, S. (2023) · Neuroscience Applied · doi:10.1016/j.nsa.2023.103923 · Cited by 18
“The emerging field of immunopsychiatry is revolutionizing our comprehension of mental illnesses, providing novel theoretical frameworks and paving the way for innovative diagnostic and therapeutic approaches (Leboyer et al., 2016; Pariante, 2017).”
InfluentialFabrazzo, M., Cipolla, S., Pisaturo, M., Camerlengo, A., Bucci, P., Pezzella, P., Coppola, N., & Galderisi, S. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13121689 · Cited by 20
Ghafori, S. S., Yousefi, Z., Bakhtiari, E., hasani, M. H. M. M., & Hassanzadeh, G. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100734 · Cited by 26
“The NLR is directly increased by cortisol, a powerful anti-inflammatory hormone, which also increases neutrophils (Pariante, 2017).”
BackgroundKurczewska, E., Ferensztajn-Rochowiak, E., Jasińska-Mikołajczyk, A., Chłopocka-Woźniak, M., & Rybakowski, J. K. (2019) · Pharmacopsychiatry · doi:10.1055/a-0695-9138 · Cited by 17
“Such dysregulation in the immune system [34] can be explained by the concept of allostasis formulated by Sterling and Eyer in 1988.”
BackgroundMedicinal Plants in the Treatment of Depression. II: Evidence from Clinical Trials
Moragrega, I., & Ríos, J. L. (2021) · Planta Medica · doi:10.1055/a-1517-6882 · Cited by 18
Immunity and psychiatric disorders: variabilities of immunity biomarkers are they specific?
Dubois, T., Reynaert, C., Jacques, D., Lepièce, B., Patigny, P., & Zdanowicz, N. (2018) · PubMed · Cited by 17
Karshikoff, B., Martucci, K. T., & Mackey, S. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.651083 · Cited by 17
“Furthermore, we hypothesized that TNFα and IL-6 levels would correlate with depressive mood (47, 56, 57) and fatigue (17, 45, 58), when controlling for other psychological factors that are well-established covariates for pain, but not with pain intensity (54, 55).”
BackgroundVasileva, L. V., Ivanovska, M. V., Murdjeva, M. A., Saracheva, K. E., & Georgiev, M. I. (2019) · Food and Chemical Toxicology · doi:10.1016/j.fct.2019.03.004 · Cited by 16
“…(PNI), i.e. immunopsychiatry refers to the interdisciplinary field that studies the heterogeneous interactions between the psycho-emotional processes, the neuroendocrine system and the immune response in the human organism (Cohen, 2006; Kim and Won, 2017; Pariante, 2015, 2017).”
BackgroundChapter 4. Psychoneuroendocrinology
Sforzini, L., Weston, F. I., & Pariante, C. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as04 · Cited by 16
Self-citationKatamanin, O. M., Tan, I. J., Barry, J., & Jafferany, M. (2024) · American Journal of Clinical Dermatology · doi:10.1007/s40257-024-00905-9 · Cited by 16
“…for mediating negative feedback for the HPA axis, pro-inflammatory cytokines, particularly interleukin (IL)-1, have been shown to cause glucocorticoid resistance, resulting in impaired negative feedback of the HPA axis, and subsequently HPA axis hyperactivity and progression of depression [10, 12].”
Biomarkers of stress resilience: A review
Paribello, P., Branchi, I., Viglione, A., Mancini, G. F., Morena, M., Campolongo, P., & Manchia, M. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104052 · Cited by 17
“…indicating that immune overactivation can diminish the effectiveness of antidepressant drugs (Benedetti et al., 2021a; Carvalho et al., 2013a; Colpo et al., 2018; Haroon et al., 2018; Pariante, 2017; Strawbridge et al., 2015), suggesting the role of inflammatory processes in antidepressant action.”
Strumila, R., Lengvenytė, A., Zdanavičius, L., Badaras, R., Dlugauskas, E., Lesinskienė, S., Matiekus, E., Marcinkevicius, M., Vencevičienė, L., Utkus, A., et al. (2024) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2024.100235 · Cited by 16
“Cortisol, the primary glucocorticoid hormone released by the adrenal gland in response to stress, is one of the most widely studied biomarkers of the HPA axis dysregulation in patients with depression and STB [14, 15].”
BackgroundLeboyer, M., Foiselle, M., Tchitchek, N., Tamouza, R., Lorenzon, R., Richard, J., Arrouasse, R., Corvoisier, P. L., Dudal, K. L., Vicaut, É., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.09.005 · Cited by 15
Halaris, A. E. (2018) · Future Neurology · doi:10.2217/fnl-2017-0039 · Cited by 14
Antidepressant-like mechanism of honokiol in a rodent model of corticosterone-induced depression
Zhang, B., Li, Y., Liu, M., Duan, X., Hu, K., Li, L., Xue, Y., & Hong-sheng, C. (2020) · Journal of Integrative Neuroscience · doi:10.31083/j.jin.2020.03.172 · Cited by 15
“Also, depression is often accompanied by inflammatory symptoms, notably increased levels of interleukin-1β (IL1β), which is likely to be associated with the inactivation of GR (Pariante, 2017).”
BackgroundAlameda, L., Levier, A., Gholam‐Rezaee, M., Golay, P., Vandenberghe, F., Delacrétaz, A., Baumann, P., Glatard, A., Dubath, C., Herane-Vives, A., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242569 · Cited by 15
“Furthermore, both inflammation [15, 16] and CT [17] have been associated with higher levels of depressive symptoms in EP patients, and depressive patients [especially those with atypical features] are at higher risk of WG independently of medication [18].”
BackgroundProtective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
Yu, Z., Kong, D., Liang, Y., Zhao, X., & Du, G. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.002 · Cited by 15
Głombik, K., Detka, J., & Budziszewska, B. (2021) · Cells · doi:10.3390/cells10061394 · Cited by 16
“However, as indicated by current studies, the disturbances of neurotransmission observed in depression may not be the primary cause but rather the consequence of metabolic alternations related mainly to the dysfunction of astrocytes, excessive action of pro-inflammatory cytokines released primarily from microglial cel…”
BackgroundWang, H., Zhang, M., Xie, Q., Yu, J. M., Yan, Q., & Yue, Q. (2019) · PeerJ · doi:10.7717/peerj.7171 · Cited by 15
Ren, Q., He, C., Sun, Y., Gao, X., Zhou, Y., Qin, T., Zhang, Z., Wang, X., Wang, J., Wei, S., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1461873 · Cited by 15
“The pathophysiology of depression is extremely complex, and currently recognized hypotheses include monoamine (Hamon and Blier, 2013), neurotrophic factor (Kishi et al., 2017), hypothalamic – pituitary – adrenal (HPA) axis (Keller et al., 2017), and cytokine (Pariante, 2017) hypotheses.”
BackgroundHe, J., Liu, F., Xu, P., Xu, T., Yu, H., Wu, B., Wang, H., Chen, J., Zhang, K., Zhang, J., et al. (2024) · Depression and Anxiety · doi:10.1155/da/6651804 · Cited by 18
“The bidirectional exacerbation of these conditions is largely driven by the intricate relationship between systemic in fl ammation and HPA axis dysfunction [66 – 68].”
Jahromi, G. G., & Rezaei, N. (2025) · Heart and Mind · doi:10.4103/hm.hm-d-24-00076 · Cited by 15
Warma, S., Lee, Y. L., Brietzke, E. M., & McIntyre, R. S. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104640 · Cited by 13
Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain
Karshikoff, B., Wåhlén, K., Åström, J., Lekander, M., Holmström, L., & Wicksell, R. K. (2023) · Biomedicines · doi:10.3390/biomedicines11030713 · Cited by 17
Sforzini, L. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100331 · Cited by 14
“A promising path arises from studies on inflammation, which has emerged as an important pathway to pathology in a significant number of subjects with MDD, and particularly with TRD (Pariante, 2017).”
Toft, H., Bramness, J. G., & Lien, L. (2022) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s357797 · Cited by 14
“Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity might be a shared pathway(20) of PTSD(21) and depression.(22) The pro- and anti-inflammatory cytokine IL-6(23) and the anti-inflammatory cytokine IL-10 are associated with both PTSD and depressive disorder.”
BackgroundO’Shields, J., Patel, D., & Mowbray, O. P. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.05.077 · Cited by 15
“For instance, while CRP has been considered a strong indicator for the inflammation system and associated with several aspects of depression (Pariante, 2017; Felger et al., 2020).”
BackgroundEmotions and Steroid Secretion in Aging Men: A Multi—Study Report
Walther, A., Waldvogel, P., Noser, E., Schoch-Ruppen, J., & Ehlert, U. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.01722 · Cited by 11
Botros, M. S., Hodgins, G. E., & Nemeroff, C. B. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813333-0.00011-1 · Cited by 14
Association between programmed death-1 pathway and major depression
Huang, K.-W., & Huang, T. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2023.2209876 · Cited by 13
“Previous studies have found that increased inflammation was associated with MD in humans (Reichenberg et al. 2001; Pariante 2017).”
BackgroundBodnaruc, A. M., Roberge, M., Giroux, I., & Aguer, C. (2024) · Endocrines · doi:10.3390/endocrines5040035 · Cited by 15
“In individuals with MDD, however, evidence suggests that elevated levels of glucocorticoids may co-exist with high levels of inflammatory cytokines [75].”
Swierczynski, A. (2019) · SciMedicine Journal · doi:10.28991/scimedj-2019-0102-5 · Cited by 17
Roles of Inflammation and Depression in the Development of Gestational Diabetes
Robakis, T. K., Aasly, L., Williams, K. E., Clark, C. E., & Rasgon, N. (2017) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-017-0131-8 · Cited by 12
Poole, L., & Steptoe, A. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.01.010 · Cited by 12
“Irrespective of the temporal sequence, it has been suggested that an inflamed-depression subtype exists (Chamberlain et al., 2019; Pariante, 2017), which may have implications for treatment responsivity.”
BackgroundInfluentialSasaki, K., Linh, T. N., Hirano, A., Tominaga, K., Nukaga, S., Nozaki, H., Arimura, T., & Isoda, H. (2022) · Food and Chemical Toxicology · doi:10.1016/j.fct.2022.113508 · Cited by 16
Silva, R. C., Martini, P. G. V., Hohoff, C., Mattevi, S., Bortolomasi, M., Abate, M., Menesello, V., Gennarelli, M., Baune, B. T., & Minelli, A. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01704-z · Cited by 15
“Most interestingly, although the TOLLIP gene showed a trend-significant association, it is related to inflammation in patients with MDD and stress-related disorders [63] and is more highly expressed in patients with MDD compared to controls, regardless of childhood trauma exposure [64].”
BackgroundThe neuroimmune mechanism of pain induced depression in psoriatic arthritis and future directions
Wang, X., Wu, L., Liu, J., Ma, C., Liu, J., & Zhang, Q. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117802 · Cited by 12
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
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