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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
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.
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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.
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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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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
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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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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.
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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
“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.
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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.
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- 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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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.
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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.
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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
“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.
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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.
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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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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.
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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
“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-citationAnacker, C., Cattaneo, A., Musaelyan, K., Zunszain, P. A., Horowitz, M., Molteni, R., Luoni, A., Calabrese, F., Tansey, K., Gennarelli, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300886110 · Cited by 319
Self-citationMondelli, V., Cattaneo, A., Murri, M. B., Forti, M. D., Handley, R., Hepgul, N., Miorelli, A., Navari, S., Papadopoulos, A. S., Aitchison, K. J., et al. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10m06745 · Cited by 307
Self-citationBiological embedding of stress through inflammation processes in childhood
Danese, A., Caspi, A., Williams, B., Ambler, A., Sugden, K., Mika, J., Werts, H., Freeman, J., Pariante, C. M., Moffitt, T. E., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.5 · Cited by 301
Self-citationCortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis
Mondelli, V., Ciufolini, S., Belvederi Murri, M., Bonaccorso, S., Di Forti, M., Giordano, A., Marques, T. R., Zunszain, P. A., Morgan, C., Murray, R. M., et al. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv028 · Cited by 286
Self-citationGenetic Contributions of Inflammation to Depression
Barnes, J., Mondelli, V., & Pariante, C. M. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.169 · Cited by 237
Self-citationBull, S. J., Huezo-Diaz, P., Binder, E. B., Cubells, J. F., Ranjith, G., Maddock, C., Miyazaki, C., Alexander, N., Hotopf, M., Cleare, A. J., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.48 · Cited by 228
Self-citationSerum and gene expression profile of cytokines in first-episode psychosis
Di Nicola, M., Cattaneo, A., Hepgul, N., Di Forti, M., Aitchison, K. J., Janiri, L., Murray, R. M., Dazzan, P., Pariante, C. M., & Mondelli, V. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.06.010 · Cited by 217
Self-citationSu, K.-P., Lai, H.-C., Yang, H.-T., Su, W.-P., Peng, C.-Y., Chang, J. P.-C., Chang, H.-C., & Pariante, C. M. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.01.008 · Cited by 205
Self-citationIntergenerational transmission of maltreatment and psychopathology: the role of antenatal depression
Plant, D. T., Barker, E. D., Waters, C. S., Pawlby, S., & Pariante, C. M. (2013) · Psychological Medicine · doi:10.1017/s0033291712001298 · Cited by 201
Self-citationDo antidepressants regulate how cortisol affects the brain?
Pariante, C. M., Thomas, S. A., Lovestone, S., Makoff, A., & Kerwin, R. W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2003.10.009 · Cited by 194
Self-citationPlant, D. T., Pariante, C. M., Sharp, D., & Pawlby, S. (2015) · British Journal of Psychiatry · doi:10.1192/bjp.bp.114.156620 · Cited by 184
Self-citationSu, K., Huang, S., Peng, C., Lai, H., Huang, C., Chen, Y.-C., Aitchison, K. J., & Pariante, C. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.11.005 · Cited by 170
Self-citationCarvalho, L. A., Torre, J. P., Papadopoulos, A. S., Poon, L., Juruena, M. F., Markopoulou, K., Cleare, A. J., & Pariante, C. M. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.10.036 · Cited by 167
Self-citationPariante, C. M., Makoff, A., Lovestone, S., Feroli, S., Heyden, A., Miller, A. H., & Kerwin, R. W. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704368 · Cited by 159
Self-citationSteroid-Independent Translocation of the Glucocorticoid Receptor by the Antidepressant Desipramine
Pariante, C. M., Pearce, B. D., Pisell, T. L., Owens, M. J., & Miller, A. H. (1997) · Molecular Pharmacology · doi:10.1124/mol.52.4.571 · Cited by 156
Self-citationNikkheslat, N., Zunszain, P. A., Horowitz, M. A., Barbosa, I. G., Parker, J. A., Myint, A.-M., Schwarz, M. J., Tylee, A. T., Carvalho, L. A., & Pariante, C. M. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.02.002 · Cited by 147
Self-citationCattaneo, A., Ferrari, C., Uher, R., Bocchio‐Chiavetto, L., Riva, M. A., & Pariante, C. M. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw045 · Cited by 130
Self-citationDepression pathogenesis and treatment: what can we learn from blood mRNA expression?
Hepgul, N., Cattaneo, A., Zunszain, P. A., & Pariante, C. M. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-28 · Cited by 127
Self-citationAntenatal depression and offspring psychopathology: the influence of childhood maltreatment
Pawlby, S., Hay, D., Sharp, D., Waters, C. S., & Pariante, C. M. (2011) · British Journal of Psychiatry · doi:10.1192/bjp.bp.110.087734 · Cited by 118
Hepgul, N., Pariante, C. M., Dipasquale, S., DiForti, M., Taylor, H., Marques, T. R., Morgan, C., Dazzan, P., Murray, R. M., & Mondelli, V. (2012) · Psychological Medicine · doi:10.1017/s0033291711002947 · Cited by 112
Self-citationPlant, D. T., Pawlby, S., Sharp, D., Zunszain, P. A., & Pariante, C. M. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.155 · Cited by 108
Self-citationPariante, C. M., Kim, R. B., Makoff, A., & Kerwin, R. W. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705357 · Cited by 89
Self-citationAntidepressant Compounds Can Be Both Pro- and Anti-Inflammatory in Human Hippocampal Cells
Horowitz, M. A., Wertz, J., Zhu, D., Cattaneo, A., Musaelyan, K., Nikkheslat, N., Thuret, S., Pariante, C. M., & Zunszain, P. A. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu076 · Cited by 82
Self-citationCarvalho, L. A., Juruena, M. F., Papadopoulos, A. S., Poon, L., Kerwin, R., Cleare, A. J., & Pariante, C. M. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.44 · Cited by 75
Self-citationPsychoneuroimmunology or immunopsychiatry?
Pariante, C. M. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00042-5 · Cited by 70
Self-citationPariante, C. M., Hye, A., Williamson, R., Makoff, A., Lovestone, S., & Kerwin, R. W. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300195 · Cited by 70
Self-citationHepgul, N., Cattaneo, A., Agarwal, K., Baraldi, S., Borsini, A., Bufalino, C., Forton, D. M., Mondelli, V., Nikkheslat, N., Lopizzo, N., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.50 · Cited by 62
Self-citationMason, B. L., Pariante, C. M., & Thomas, S. A. (2008) · Endocrinology · doi:10.1210/en.2008-0041 · Cited by 60
Self-citationCarvalho, L. A., Garner, B., Dew, T. K., Fazakerley, H., & Pariante, C. M. (2010) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2010.02.006 · Cited by 58
Self-citationPariante, C. M., Papadopoulos, A. S., Poon, L., Cleare, A. J., Checkley, S. A., English, J., Kerwin, R. W., & Lightman, S. L. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1925-4 · Cited by 52
Self-citationYau, J. L. W., Noble, J., Thomas, S., Kerwin, R., Morgan, P. E., Lightman, S., Seckl, J. R., & Pariante, C. M. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301389 · Cited by 46
Self-citationEffects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers
Handley, R., Mondelli, V., Zelaya, F., Marques, T., Taylor, H., Reinders, A. A. T. S., Chaddock, C., McQueen, G., Hubbard, K., Papadopoulos, A., et al. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.03.039 · Cited by 42 · cited 2×
“…is also relevant for patients with psychotic disorders, such as schizophrenia, by affecting physical health, brain structure, clinical outcome and the action of antipsychotics (Di Nicola et al., 2013; Handley et al., 2016; Hepgul et al., 2012; Mondelli et al., 2011, 2015; Russell et al., 2015).”
Pariante, C. M., Pearce, B. D., Pisell, T. L., Sanchez, C. I., Po, C., Su, C., & Miller, A. H. (1999) · Endocrinology · doi:10.1210/en.140.9.4359 · Cited by 40
Self-citationRussell, A., Ciufolini, S., Gardner-Sood, P., Bonaccorso, S., Gaughran, F., Dazzan, P., Pariante, C. M., & Mondelli, V. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.06.004 · Cited by 37
Self-citationN-acetyl-cysteine prevents toxic oxidative effects induced by IFN-α in human neurons
Alboni, S., Gibellini, L., Montanari, C., Benatti, C., Benatti, S., Tascedda, F., Brunello, N., Cossarizza, A., & Pariante, C. M. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000266 · Cited by 35
Self-citationPariante, C. M., Alhaj, H. A., Arulnathan, V. E., Gallagher, P., Hanson, A., Massey, E., & McAllister-Williams, R. H. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.08.011 · Cited by 33
Self-citationInflammatory insults and mental health consequences: does timing matter when it comes to depression?
Preez, A. D., Leveson, J., Zunszain, P. A., & Pariante, C. M. (2016) · Psychological Medicine · doi:10.1017/s0033291716000672 · Cited by 29
Self-citationMason, B. L., Thomas, S. A., Lightman, S. L., & Pariante, C. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.008 · Cited by 9
Self-citationPsychological status and immunological parameters of institutionalized aged.
Bartoloni, C., Guidi, L., Antico, L., Pariante, C. M., Giovanni, A. D., Пили, Р., Cursi, F., Tricerri, A., Tempesta, E., & Frasca, D. (1991) · PubMed · Cited by 6
Self-citationPM309. Methamphetamine induced changes of monoamine neurotransmission in 5-HT1B KO mice
Moriya, Y., Hagino, Y., Hall, S. F., Hen, R., Ikeda, K., Kasahara, Y., Sora, I., & Uhl, G. R. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw041.309 · Cited by 1
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Neuroinflammation and depression: A review
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“…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
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“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.”
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“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].”
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“through pathways, such as inflammation, interaction effects, or cognitive biases) [161,182,258,358, 362,380].”
Background
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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