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.
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review reflects on 20 years of the author's laboratory research on why a subgroup of depressed patients shows both increased inflammation and HPA-axis abnormalities, proposing glucocorticoid resistance as the linking mechanism. It argues that inflammation in depression is often a "biological scar" of early-life stress and can be used to predict antidepressant non-response.
Key findings
- Increased inflammation and HPA-axis hyperactivity coexist in depression despite cortisol's expected anti-inflammatory action; the author's in vitro work showed IL-1 induces glucocorticoid resistance (impaired GR translocation), while antidepressants reverse it.
- In the GENDEP sample, depressed patients showed increased mRNA of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, MIF) and reduced IL-4, together with reduced GR mRNA and increased FKBP5 — a molecular signature of GR resistance.
- In depressed patients with coronary heart disease, higher IL-6 mRNA and CRP and reduced GR mRNA were found, but associated with HPA-axis hypoactivity rather than hyperactivity.
- Baseline mRNA levels of IL-1, MIF and TNF-alpha predicted roughly half the variance in antidepressant response; in a replication using absolute mRNA values, cut-offs predicted non-response with positive predictive values and specificity of 100%.
- Early-life adversity (childhood maltreatment, and prenatal maternal depression in the South London Child Development Cohort) was associated with raised inflammation markers (CRP, white cell counts, fibrinogen); a randomized controlled trial found prophylactic EPA/DHA prevented or delayed interferon-alpha-induced depression.
Methods
- Design: narrative, self-referential review of the author's own 20 years of research (1991–2017), framed around the 2015 Anna-Monika Foundation Award.
- Evidence base: in vitro models (mouse fibroblasts, human peripheral blood mononuclear cells, human neurons/hippocampal progenitor cells), animal studies, and clinical cohorts including GENDEP, the Dunedin study, and the South London Child Development Cohort, plus an RCT of omega-3 fatty acids.
- Analysis: descriptive synthesis of findings across these studies; no systematic search or meta-analysis is described.
Limitations
- Stated: the review is explicitly self-referential ("the narrative and the citations are self-referential"), and the author lists outstanding unanswered questions, including the epigenetic mechanisms linking early-life events to long-term inflammation, how anti-inflammatories help depression, and whether normalising GR function is helpful for patients.
- Evident from the text: as a single-laboratory narrative review it is not a systematic or exhaustive synthesis, and several cited findings (e.g., the 100% predictive values, preliminary genetic and in utero evidence) are described by the author as preliminary or requiring replication.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 64 cited sources checked · 0 supported · 0 flagged
- Findingcitation
These same subjects have glucocorticoid resistance, as shown by reduced in vitro ability of their peripheral blood mononuclear cells to respond to dexamethasone and cortisol during an immune stimulus.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Carvalho et al., 2009
Not checked in the free run.
- Findingcitation
Patients with the highest IL-6 levels are the least likely to respond to antidepressants.
“Patients with the highest IL-6 levels are also the least likely to respond to antidepressants (Carvalho et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Carvalho et al., 2013 source
Not checked in the free run.
- Findingcitation
In 2008, increased plasma cortisol levels and increased inflammation (plasma IL-6) were described in the same depressed individuals, a group of severely depressed inpatients with treatment-resistant depression.
“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)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Carvalho et al., 2008 source
Not checked in the free run.
- Findingcitation
In the GENDEP sample, patients have molecular evidence of GR resistance as shown by reduced expression of GR mRNA together with increased expression of the GR chaperone protein FKBP5.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cattaneo et al., 2013 source
Not checked in the free run.
- Findingown data
In the GENDEP sample, increased inflammation in depression was replicated as shown by increased mRNA expression of proinflammatory cytokines (IL-1, IL-6, TNF-alpha and MIF) together with reduced expression of anti-inflammatory cytokine IL-4.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cattaneo et al., 2013 source
Not checked in the free run.
- Findingcitation
p-glycoprotein regulates the effects of antidepressants on GR expression.
“we were able to demonstrate that p-glycoprotein regulates the effects of antidepressants on GR expression (Yau et al., 2007)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yau et al., 2007 source
Not checked in the free run.
- Findingcitation
In healthy volunteers, antidepressants reverse GR resistance, increasing GR function as measured by HPA axis negative feedback and the effects of cortisol on the EEG.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Pariante et al., 2004a
Not checked in the free run.
- cites Pariante et al., 2012 source
Not checked in the free run.
- Findingcitation
The detrimental effects of these inflammatory stimuli can be reversed by antidepressant treatments including inhibitors of kynurenine pathways, antioxidants and mitochondrial modulators, and omega-3 polyunsaturated fatty acids.
“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”
Quote in the paperSubstantial claim0 of 3 sources checked - Findingcitation
The effect of IL-1 and interferon-alpha on neurogenesis and survival is mediated by increased production of neurotoxic tryptophan metabolites and increased oxidative stress.
“an effect that is mediated by an increased production of neurotoxic tryptophan metabolites as well as an increased oxidative stress”
Quote in the paperSubstantial claim0 of 3 sources checked - Findingcitation
Antidepressants increase neurogenesis by activating a downstream cascade of second messenger mechanisms that requires the GR.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Anacker et al., 2011 source
Not checked in the free run.
- Findingown data
In depressed patients with coronary heart disease, these findings were not associated with HPA axis hyperactivity but rather with hypoactivity.
“these findings were not associated with HPA axis hyperactivity but rather with hypoactivity.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nikkheslat et al., 2015 source
Not checked in the free run.
- Findingcitation
Cortisol decreases neurogenesis via activation and upregulation of SGK1, leading to inhibition of TGFβ-SMAD2/3 and Hedgehog signalling.
“cortisol decreases neurogenesis via activation and upregulation of the GR-stimulated gene, serum-and glucocorticoid-inducible kinase 1 (SGK1), leading to inhibition of TGFβ-SMAD2/3-and Hedgehog signalling (Anacker et al., 2013a(Anacker et al., , 2013b)).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Anacker et al., 2013a
Not checked in the free run.
- cites Anacker et al., 2013b
Not checked in the free run.
- Findingcitation
The association between early life trauma and increased inflammation was replicated in 12-year-old children.
“we have been able to replicate the association between early life trauma and increased inflammation also in 12-year-old children (Danese et al., 2011)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Danese et al., 2011 source
Not checked in the free run.
- Findingcitation
The association between early life trauma and increased inflammation was replicated in young adults exposed to stress in utero.
“and, most interestingly, in young adults who have been exposed to stress not in childhood but even earlier: in utero (Plant et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Plant et al., 2016 source
Not checked in the free run.
- Findingcitation
Increased inflammation clusters with metabolic risk biomarkers such as being overweight or presenting with high blood pressure, high total cholesterol and high glycated hemoglobin.
“the increased inflammation clusters with metabolic risk biomarkers such as being overweight or presenting with high blood pressure, high total cholesterol and high glycated hemoglobin (Danese et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Danese et al., 2009 source
Not checked in the free run.
- Findingcitation
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.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Danese et al., 2007 source
Not checked in the free run.
- Findingcitation
Exposure to maternal depression during pregnancy (but not in the postpartum period) doubles the risk of the offspring developing depression and other mental disorders in adolescence.
“exposure to maternal depression during pregnancy (but not in the postpartum period) doubles the risk of the offspring developing themselves depression and other mental disorders in adolescence (Pawlby et al., 2011)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pawlby et al., 2011 source
Not checked in the free run.
- Findingcitation
Prophylactic treatment with EPA and DHA prevents or delays the onset of interferon-alpha-induced depression.
“in a subsequent clinical trial we have recently demonstrated that prophylactic treatment with EPA and DHA prevents or delays the onset of interferon-alpha-induced depression (Su et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Su et al., 2014
Not checked in the free run.
- Findingcitation
The functional G-174C polymorphism (rs1800795) in the promoter region of the IL-6 gene predicts depressive symptoms in patients taking interferon-alpha for chronic viral hepatitis.
“the functional G-174C polymorphism (rs1800795) in the promoter region of the IL-6 gene predicts depressive symptoms in patients taking interferon-alpha for chronic viral hepatitis (Bull et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bull et al., 2009 source
Not checked in the free run.
- Findingcitation
The association between maternal depression during pregnancy and offspring depression is mediated, at least in part, by an increased risk of the offspring being exposed to maltreatment and other stressful events in childhood.
“association that is mediated, at least in part, by an increased risk of the offspring being exposed to maltreatment and other stressful events in childhood (Plant et al., 2013(Plant et al., , 2015)).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Findingcitation
Depressed patients who do not respond to prescribed antidepressants (escitalopram or desipramine) have higher baseline mRNA levels of IL-1, MIF and TNF-alpha.
“We found that depressed patients who do not go on to respond to the prescribed antidepressants (escitalopram or desipramine) have higher baseline mRNA levels of IL-1, MIF and TNF-alpha.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cattaneo et al., 2013 source
Not checked in the free run.
- Findingcitation
Carriers of the two 'at risk' PLA2 and COX2 genotypes have lower levels of omega-3 fatty acids DHA and EPA before and during IFN-α treatment.
“carriers of the two 'at risk' PLA2 and COX2 genotypes also have lower levels of the omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), before and during IFN-α treatment (Su et al., 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Su et al., 2010
Not checked in the free run.
- Findingcitation
Two polymorphisms in genes regulating prostaglandin synthesis, the BanI polymorphism of cPLA2 and the COX2 rs4648308 polymorphism, regulate the risk of developing interferon-alpha induced depression.
“two polymorphisms in genes regulating prostaglandin synthesis, the BanI polymorphism of the cytosolic phospholipase A2 (cPLA2) and the COX2 rs4648308 polymorphism in the cyclooxygenase 2 (COX-2) genes, also regulate the risk of developing interferonalpha induced depression (Su et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Su et al., 2010
Not checked in the free run.
- Findingcitation
Offspring exposed to maternal depression in utero, now young adults, have increased inflammation as shown by raised CRP levels.
“these same offspring exposed to maternal depression in utero, now young adults, have increased inflammation as shown by raised CRP levels (Plant et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Plant et al., 2016 source
Not checked in the free run.
- Findingcitation
Patients who develop depression during interferon-alpha treatment present a hyperactive immune response that is evident by measuring mRNA but not plasma cytokines.
“patients who develop depression during this immune challenge present a hyperactive immune response that is evident by measuring mRNA but not plasma cytokines (Hepgul et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hepgul et al., 2016 source
Not checked in the free run.
- Interpretationreasoning
Different activators of the GR induce different patterns of GR phosphorylation and activation, leading to different sets of downstream GR-stimulated genes.
“This apparent contradiction is due to the fact that different activators of the GR induce different patterns of GR phosphorylation and activation, eventually leading to different sets of downstream GR-stimulated genes.”
Quote in the paperSubstantial claim - Interpretationreasoning
Increased inflammation is present in a subgroup of depressed patients who have a neurodevelopmentally-based form of depression, originating from exposure to stress (or possibly directly to inflammation) early in childhood or even in utero.
“Taken together, all these lines of evidence indicate that increased inflammation is present in a subgroup of depressed patients who have a neurodevelopmentally-based form of depression, originating from exposure to stress (or possibly directly to inflammation) early in childhood or even in utero.”
Quote in the paperSubstantial claim - Interpretationcitation
Measurement of blood mRNA immune genes is a reliable and clinically significant biomarker in psychoneuroimmunology, complementing (and at times surpassing) routine measurement of serum/plasma cytokines.
“have established the measurement of blood mRNA immune genes as a reliable and clinically significant biomarker in the context of psychoneuroimmunology, to complement (and at times surpass) the routine measurement of serum/plasma cytokines (Hepgul et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hepgul et al., 2013 source
Not checked in the free run.
- Interpretationown data
Increased inflammation characterizes a subgroup of depressed patients that is less likely to respond to conventional antidepressants.
“These series of studies not only have provided consistent evidence that increased inflammation characterizes a subgroup of depressed patients that is less likely to respond to conventional antidepressants”
Quote in the paperSubstantial claim - Premisecitation
An activated inflammatory system is relevant for patients with psychotic disorders, such as schizophrenia, by affecting physical health, brain structure, clinical outcome and the action of antipsychotics.
“an activated inflammatory system is also relevant for patients with psychotic disorders, such as schizophrenia, by affecting physical health, brain structure, clinical outcome and the action of antipsychotics”
Quote in the paperNot a substantial claim0 of 3 sources checked
- May combine two claims. 19
- Classified as probably not a substantial claim. 1
May combine two claims.
FindingcitationThe effects of antidepressants potentiating GR translocation and function are mediated both directly through steroid-independent activation of the GR and indirectly by inhibition of the p-glycoprotein transporter that expels cortisol from cells.
“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).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Pariante et al., 2001
Not checked in the free run.
- cites Pariante et al., 2003a
Not checked in the free run.
- cites Pariante et al., 2003b
Not checked in the free run.
May combine two claims.
FindingcitationAntidepressants in vitro increase GR activation and function, reversing glucocorticoid resistance.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pariante et al., 1997 source
Not checked in the free run.
May combine two claims.
FindingcitationIn vitro, the effects of antidepressants on GR translocation and function are common to all tested antidepressants and are present in mouse fibroblasts and rat neurons.
“these effects are common to all tested antidepressants and are present not only in mouse fibroblasts but also in rat neurons”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Pariante et al., 2001
Not checked in the free run.
- cites Pariante et al., 2003a
Not checked in the free run.
- cites Pariante et al., 2003b
Not checked in the free run.
May combine two claims.
FindingcitationIncubating L929 mouse fibroblasts with the pro-inflammatory cytokine IL-1 leads to glucocorticoid resistance, i.e., impairment of GR activation and translocation from the cytoplasm to the nucleus, resulting in reduced expression of GR-stimulated genes.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pariante et al., 1999 source
Not checked in the free run.
May combine two claims.
Findingcitationp-glycoprotein and antidepressants do not regulate cortisol levels in the brain.
“but not, however, that pglycoprotein or indeed antidepressants regulate cortisol levels in the brain (Mason et al., 2008(Mason et al., , 2011)).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Mason et al., 2008
Not checked in the free run.
- cites Mason et al., 2011
Not checked in the free run.
May combine two claims.
Findingown dataDepressed patients with coronary heart disease have higher inflammation (higher IL-6 mRNA and higher CRP) together with reduced expression of GR mRNA.
“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”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nikkheslat et al., 2015
Not checked in the free run.
May combine two claims.
FindingcitationIL-1 and interferon-alpha reduce human neurogenesis and human neuronal survival.
“we found that two proinflammatory cytokines, IL-1 and interferon-alpha, reduce human neurogenesis and human neuronal survival”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Alboni et al., 2013
Not checked in the free run.
- cites Horowitz et al., 2014
Not checked in the free run.
- cites Zunszain et al., 2012 source
Not checked in the free run.
May combine two claims.
FindingcitationAntidepressants increase neurogenesis via a GR-dependent mechanism that requires PKA signalling and upregulation of genes such as p11 and CDK2 inhibitors p27 and p57.
“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)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Anacker et al., 2011 source
Not checked in the free run.
May combine two claims.
FindingcitationBoth antidepressants and cortisol require the GR to exert their effects on neurogenesis, with antidepressants activating GR to increase neurogenesis and cortisol activating GR to decrease neurogenesis.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Anacker et al., 2011 source
Not checked in the free run.
- cites Anacker et al., 2013a
Not checked in the free run.
- cites Anacker et al., 2013b
Not checked in the free run.
May combine two claims.
FindingcitationAntidepressant-induced upregulation of p11 and cortisol-induced upregulation of SGK1 were replicated in the blood (mRNA) of depressed patients, and cortisol-induced downregulation of TGFβ-SMAD2/3 and Hedgehog signalling was replicated in the hippocampus of adult rats exposed to prenatal stress.
“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)).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Anacker et al., 2013a
Not checked in the free run.
- cites Anacker et al., 2013b
Not checked in the free run.
May combine two claims.
FindingcitationIncreased 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.
“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)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Danese et al., 2008 source
Not checked in the free run.
May combine two claims.
FindingcitationIn a second independent cohort, the predictive ability of IL-1 and MIF was confirmed and extended, and cut-off values for absolute mRNA measures accurately predict response probability at an individual level, with positive predictive values and specificity for nonresponders of 100%.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cattaneo et al., 2016
Not checked in the free run.
May combine two claims.
FindingcitationThe levels of IL-1, MIF and TNF-alpha together predict approximately half of the variance in antidepressant response, with IL-1 and MIF explaining most of the variance.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cattaneo et al., 2013 source
Not checked in the free run.
May combine two claims.
PremisecitationIn depression, a dysfunction of the glucocorticoid receptor leads to impaired HPA axis negative feedback (glucocorticoid resistance), which in turn leads to HPA axis hyperactivity.
“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).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Pariante and Lightman, 2008 source
Not checked in the free run.
- cites Pariante and Miller, 2001
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe molecular signature underlying GR resistance and increased inflammation in depression is reduced GR expression together with decreased GR responsivity (as FKBP5 binds to GR and maintains it in an unresponsive state).
“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).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataGlucocorticoid resistance, cortisol hypersecretion and increased inflammation are coexistent and related biological abnormalities.
“These findings confirmed the notion that glucocorticoid resistance, cortisol hypersecretion and increased inflammation are indeed coexistent and related biological abnormalities.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThis biological picture introduces a different type of GR resistance: an ineffective GR together with lower levels of cortisol.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nikkheslat et al., 2015
Not checked in the free run.
May combine two claims.
InterpretationcitationIncreased inflammation is a 'biological scar' of early exposure to high levels of stress, originating in childhood and characterised by abnormalities in both mental and physical health.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Baumeister et al., 2016 source
Not checked in the free run.
May combine two claims.
PremisecitationGenetic 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.
“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).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Barnes et al., 2017
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S4 (based).
InterpretationreasoningThe strong impact of the immune system on emotions and behaviour demonstrates that mental health is the health of the whole body.
“The strong impact of the immune system on emotions and behaviour demonstrates that mental health is the health of the whole body.”
Quote in the paperNot a substantial claim
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?
Abundant evidence supports the role of neuroinflammation and altered immune processes in the aetiopathogeneses of various mental conditions.
“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
Section 5 links inflammation and altered immune responses to risk of depression, particularly in a subgroup of patients. Section 6 says an activated inflammatory system is relevant to psychotic disorders such as schizophrenia, but discusses effects on health, brain structure and outcomes rather than establishing a role in their aetiopathogenesis. The paper therefore supports the claim for depression, but not its broader implication about the origins of various mental conditions or neuroinflammation specifically. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSome of these biological processes participate in disease pathogenesis in parallel, such as the redox system and glutamatergic/GABAergic imbalance, or the immune system and the stress response.
“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
Adverse childhood or early life experiences, such as conflict with parents, early exposure to traumatic life events, bullying, and childhood trauma, were found to increase the risk of depression.
“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.
Cited 2008 study reports the opposite direction of GR effect
MinorThe text presents the 2008 human-blood-cell study as showing an antidepressant-induced increase in GR function. The cited reference's title says clomipramine reduced GR function in healthy subjects and did not do so in patients with major depression.
“Two subsequent papers demonstrated similar findings in human peripheral blood mononuclear cells (Carvalho et al., 2008(Carvalho et al., , 2010)).”
“Clomipramine in vitro reduces glucocorticoid receptor function in healthy subjects but not in patients with major depression.”
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 · see citing works
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× · see citing works
“…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 · see citing works
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 · see citing works
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 · see citing works
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× · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 313 · see citing works
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 305 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 165 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 129 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 78 · see citing works
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 · see citing works
Self-citationPsychoneuroimmunology or immunopsychiatry?
Pariante, C. M. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00042-5 · Cited by 70 · see citing works
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 · see citing works
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 · see citing works
Self-citationMason, B. L., Pariante, C. M., & Thomas, S. A. (2008) · Endocrinology · doi:10.1210/en.2008-0041 · Cited by 59 · see citing works
Self-citationde Carvalho, 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 56 · see citing works
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 51 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Neuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107 · see citing works
“…is a major risk factor for MDD. Chronic stress has reliably been associated with HPA axis abnormalities along with the salient features of inflammation in patients and animal models (Espinosa-Oliva et al., 2011; Farooq et al., 2018; Laugeray et al., 2016; Pariante, 2017; Surget et al., 2011).”
BackgroundInfluentialMicrobiome–host systems interactions: protective effects of propionate upon the blood–brain barrier
Hoyles, L., Snelling, T., Umlai, U.-K., Nicholson, J. K., Carding, S. R., Glen, R. C., & McArthur, S. (2018) · Microbiome · doi:10.1186/s40168-018-0439-y · Cited by 591 · see citing works
“That inflammation contributes to depression has become clearer over recent years [78]; hence, it is conceivable that the anti-inflammatory effects of propionate we describe may underlie at least part of the protective effects of prebiotic treatment, a proposal which, though speculative, is deserving of further study.”
BackgroundMolecular pathways of major depressive disorder converge on the synapse
Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504 · see citing works
“Inflammation Several studies have found that MDD and a dysregulation of the inflammatory process are associated in a bidirectional pathway (“cytokine theory of MDD”) [125].”
BackgroundBiological, Psychological, and Social Determinants of Depression: A Review of Recent Literature
Remes, O., Mendes, J. F., & Templeton, P. (2021) · Brain Sciences · doi:10.3390/brainsci11121633 · Cited by 482 · see citing works
“through pathways, such as inflammation, interaction effects, or cognitive biases) [161,182,258,358, 362,380].”
BackgroundThe HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?
Misiak, B., Łoniewski, I., Marlicz, W., Frydecka, D., Szulc, A., Rudzki, L., & Samochowiec, J. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109951 · Cited by 343 · see citing works
Tian, P., O’Riordan, K. J., Lee, Y. K., Wang, G., Zhao, J., Zhang, H., Cryan, J. F., & Chen, W. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100216 · Cited by 297 · see citing works
“…alteration in glucocorticoid receptor gene expression can lead to glucocorticoid resistance and is also coincident with a high level of inflammation, consistent with previous reports (Cohen et al., 2012; Dendoncker and Libert, 2017; Keller et al., 2017; Pariante, 2017; Pariante and Lightman, 2008).”
Bernaras, E., Jaureguizar, J., & Garaigordobil, M. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00543 · Cited by 243 · see citing works
The self in context: brain systems linking mental and physical health
Koban, L., Gianaros, P. J., Hedy Kober, A., & Wager, T. D. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00446-8 · Cited by 241 · see citing works
Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment
Mazza, M. G., Palladini, M., Poletti, S., & Benedetti, F. (2022) · CNS Drugs · doi:10.1007/s40263-022-00931-3 · Cited by 233 · see citing works
“However, high levels of glucocorticoids may, in the long term, cause resistance to glucocorticoid feedback on the HPA axis, thus allowing pro-inflammatory signaling pathways to avoid normal feedback inhibition [90].”
BackgroundOsborne, S., Biaggi, A., Chua, T.-E., Preez, A. D., Hazelgrove, K. M., Nikkheslat, N., Previti, G., Zunszain, P. A., Conroy, S., & Pariante, C. M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.06.017 · Cited by 207 · see citing works
“Indeed, studies of symptoms of depression in pregnancy have provided some evidence of the same altered inflammation and HPA axis activity found in depression outside of pregnancy (Pariante and Lightman, 2008; Miller and Raison, 2016; Pariante, 2017).”
Self-citationMolecular links between endocrine, nervous and immune system during chronic stress
Zefferino, R., Di Gioia, S., & Conese, M. (2021) · Brain and Behavior · doi:10.1002/brb3.1960 · Cited by 204 · see citing works
“, in depression) cause resistance to glucocorticoid feedback on the HPA axis, and this developed glucocorticoid resistance allows the escape of proinflammatory signaling pathways from normal feedback inhibition (Pariante, 2017).”
BackgroundZhang, Y., Long, Y., Yu, S., Li, D., Yang, M., Guan, Y., Zhang, D., Wan, J., Liu, S., Shi, A., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105376 · Cited by 205 · see citing works
Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review
Lwin, M. N., Serhal, L., Holroyd, C. R., & Edwards, C. J. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00217-4 · Cited by 201 · see citing works
“In RA, inflammatory markers including CRP, ESR and pro-inflammatory cytokines TNF-a , IL-1, Il-6 and IFN-a levels are elevated, and such increased levels of inflammation are regarded as a ‘‘biological scar’’ that increases the risk of depression [69].”
The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder
Woelfer, M., Kasties, V., Kahlfuss, S., & Walter, M. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.034 · Cited by 171 · see citing works
Inflammatory mediators in major depression and bipolar disorder
Poletti, S., Mazza, M. G., & Benedetti, F. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02921-z · Cited by 179 · see citing works
Qin, Z., Shi, D., Li, W., Cheng, D., Zhang, Y.-D., Zhang, S., Tsoi, B., Zhao, J., Wang, Z., & Zhang, Z. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02744-7 · Cited by 169 · see citing works
Role of inflammation in depression relapse
Liu, C., Zhang, G., Li, B., Li, M., Woelfer, M., Walter, M., & Wang, L. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1475-7 · Cited by 166 · see citing works
Giacobbe, J., Benoiton, B., Zunszain, P., Pariante, C. M., & Borsini, A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00122 · Cited by 159 · see citing works
“Over the last few decades, inflammation has been identified as one of the main pathophysiological mechanisms underlying psychiatric conditions (1, 2).”
BackgroundSelf-citationBottaccioli, A. G., Bottaccioli, F., & Minelli, A. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13728 · Cited by 161 · see citing works
Sadeghi, O., Keshteli, A. H., Afshar, H., Esmaillzadeh, A., & Adibi, P. (2021) · Nutritional Neuroscience · doi:10.1080/1028415x.2019.1620425 · Cited by 157 · see citing works
“Mediterranean diet has been associated with lower levels of circulating inflammation, which is strongly linked with psychological disorders [61,62].”
BackgroundMolecular Mechanisms of Neurogenic Inflammation of the Skin
Marek‐Józefowicz, L., Nedoszytko, B., Grochocka, M., Zmijewski, M. A., Czajkowski, R., Cubała, W. J., & Slominski, A. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055001 · Cited by 160 · see citing works
Physical Exercise and Neuroinflammation in Major Depressive Disorder
Ignácio, Z. M., da Silva, R. S., Plissari, M. E., Quevedo, J., & Réus, G. Z. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01670-1 · Cited by 153 · see citing works
The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects
Marek‐Józefowicz, L., Czajkowski, R., Borkowska, A., Nedoszytko, B., Zmijewski, M. A., Cubała, W. J., & Slominski, A. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020669 · Cited by 161 · see citing works
“Two major types of receptors can help the HPA axis exert its fe dback function: the glucocorticoid (GR) and mineralocorticoid receptor (MR) [102].”
BackgroundThe role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
“…that clinical depression is a highly heterogeneous disorder with multiple, intertwined aetiologies linked to alterations in brain plasticity and monoamine functions in general, as well as disturbances in the immune system and the HPA axis (Miller & Raison, 2016; Pariante, 2017; Levy et al., 2018).”
BackgroundChildhood trauma in mood disorders: Neurobiological mechanisms and implications for treatment
Jaworska-Andryszewska, P., & RYBAKOWSKI, J. K. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.10.004 · Cited by 128 · see citing works
Molecular aspects of depression: A review from neurobiology to treatment
Boas, G. R. V., de Lacerda, R. B., Paes, M. M., Gubert, P., Almeida, W. L. D. C., Rescia, V. C., Galdino, P. M., de Carvalho, A. A. V., & Oesterreich, S. A. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.02.024 · Cited by 128 · see citing works
Song, Q., Fan, C., Wang, P., Li, Y., Yang, M., & Yu, S. Y. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1377-0 · Cited by 124 · see citing works
Childhood trauma, HPA axis activity and antidepressant response in patients with depression
Nikkheslat, N., McLaughlin, A. P., Hastings, C., Zajkowska, Z., Nettis, M. A., Mariani, N., Enache, D., Lombardo, G., Pointon, L., Cowen, P. J., et al. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.11.024 · Cited by 124 · see citing works
“Indeed, attenuated glucocorticoid responsiveness, so called glucocorticoid resistance, has been consistently observed in MDD patients presenting coexistence of hypercortisolemia and inflammation (Pariante, 2017, Perrin et al., 2019, Stewart et al., 2009).”
BackgroundInfluentialSelf-citationBiomarkers of Pathological Dissociation: A Systematic Review
Roydeva, M. I., & Reinders, A. A. T. S. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.019 · Cited by 116 · see citing works
Cattaneo, A., Ferrari, C., Turner, L., Mariani, N., Enache, D., Hastings, C. N. M., Kose, M., Lombardo, G., McLaughlin, A. P., Nettis, M. A., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00874-7 · Cited by 115 · see citing works
Self-citationGustafsson, H., Sullivan, E. L., Nousen, E. K., Sullivan, C. A., Huang, E., Rincon, M. P., Nigg, J. T., & Loftis, J. M. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.011 · Cited by 109 · see citing works
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106 · see citing works
“We suggest that a treatment approach should consider the inflammatory history of the individual (with the standard treatment protocol available), given that pre-existent dysregulated inflammatory activity can modulate treatment outcomes (Uher et al., 2014; Lasselin et al., 2016b; Carvalho et al., 2012; Pariante, 2017).”
Kremer, M., Yalçın, İ., Goumon, Y., Wurtz, X., Nexon, L., Daniel, D., Megat, S., Ceredig, R. A., Ernst, C., Turecki, G., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1004-18.2018 · Cited by 104 · see citing works
The role of yoga in inflammatory markers
Estevao, C. (2022) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2022.100421 · Cited by 94 · see citing works
“However, the study found no significant effects in TNF- α or cortisol levels, which are, interestingly, regulated independently of IL-6 (Pariante, 2017; Del Giudice and Gangestad, 2018).”
BackgroundChemokine alterations in bipolar disorder: A systematic review and meta-analysis
Misiak, B., Bartoli, F., Carrà, G., Małecka, M., Samochowiec, J., Jarosz, K., Banik, A., & Stańczykiewicz, B. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.04.013 · Cited by 102 · see citing works
“Available evidence indicates that treatment-resistance and a history of childhood trauma are well-known correlates of subclinical inflammation in depression and thus they might account for variability of cytokine levels in this group of patients (Pariante, 2017).”
Effects of SSRIs on Peripheral Inflammatory Cytokines in Patients with Generalized Anxiety Disorder
Hou, R., Ye, G., Liu, Y., Chen, X., Pan, M., Zhu, F., Fu, J., Fu, T., Liu, Q., Gao, Z., et al. (2019) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2019.06.001 · Cited by 97 · see citing works
Fan, C., Song, Q., Wang, P., Li, Y., Yang, M., & Yu, S. Y. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00516 · Cited by 99 · see citing works
“…increased inflammation, previous study reported that the increased inflammation is mainly present in a subgroup of depressed patients who exposure to stress early in childhood or even in utero, and these depressed patients is less likely to respond to conventional antidepressants (Pariante, 2017).”
BackgroundPerrin, A. J., Horowitz, M. A., Roelofs, J., Zunszain, P. A., & Pariante, C. M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00423 · Cited by 98 · see citing works
“The conflicting nature of the primary literature, combined with a consensus in the field that such a positive association indeed exists (11, 57), lead us to conduct the systematic review and meta-analytic work described above.”
BackgroundMethodResultInfluentialSelf-citationNeuroinflammation in Post-Traumatic Stress Disorder
Lee, D.-H., Lee, J.-Y., Hong, D.-Y., Lee, E.-C., Park, S.-W., Lee, M. R., & Oh, J. S. (2022) · Biomedicines · doi:10.3390/biomedicines10050953 · Cited by 97 · see citing works
Short-term PM2.5 exposure and emergency hospital admissions for mental disease
Lee, S., Lee, W., Kim, D., Kim, E., Myung, W., Kim, S., & Kim, H. (2019) · Environmental Research · doi:10.1016/j.envres.2019.01.036 · Cited by 96 · see citing works
Tayab, M. A., Islam, M. N., Chowdhury, K. A. A., & Tasnim, F. M. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112668 · Cited by 98 · see citing works
Treatment-Resistant Depression Revisited: A Glimmer of Hope
Halaris, A. E., Sohl, E., & Whitham, E. A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020155 · Cited by 98 · see citing works
“This feedback loop increasingly fails due to a reduction in both the number of expressed GRs and GR desensitization [32].”
BackgroundWang, X., Li, Y., Wu, L., Xiao, S., Ji, Y., Tan, Y., Jiang, C., & Zhang, G. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111065 · Cited by 95 · see citing works
Stress and coping in women with breast cancer:unravelling the mechanisms to improve resilience
Borgi, M., Collacchi, B., Ortona, E., & Cirulli, F. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.011 · Cited by 90 · see citing works
Misiak, B., Wójta-Kempa, M., Samochowiec, J., Schiweck, C., Aichholzer, M., Reif, A., Samochowiec, A., & Stańczykiewicz, B. (2022) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2022.110581 · Cited by 93 · see citing works
“Indeed, this observation has been made in patients with depression (Pariante, 2017).”
Oleoylethanolamide, Neuroinflammation, and Alcohol Abuse
Orío, L., Alén, F., Pavón, F. J., Serrano, A., & García‐Bueno, B. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00490 · Cited by 90 · see citing works
“…all these alterations can even affect other multifaceted processes, such as monoaminergic and glutamatergic neurotransmission (Ogyu et al., 2018), neuroendocrine responses (Pariante, 2017), cognition (Skaper et al., 2014), and ultimately behavior (Dantzer et al., 2008; McCusker and Kelley, 2013).”
BackgroundIob, E., Lacey, R. E., & Steptoe, A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.12.019 · Cited by 86 · see citing works
“Please cite this article as: Eleonora Iob, Rebecca Lacey and Andrew Steptoe, Brain, Behavior, and Immunity, https://doi.org/10.1016/j.bbi.2019.12.019 be concurrent in the context of chronic stress (Pariante, 2017).”
InfluentialDionysopoulou, S., Charmandari, E., Bargiota, Α., Vlahos, N., Mastorakos, G. P., & Valsamakis, G. (2021) · Nutrients · doi:10.3390/nu13020498 · Cited by 88 · see citing works
Evolution of a maternal immune activation (mIA) model in rats: Early developmental effects
Murray, K. N., Edye, M. E., Manca, M., Vernon, A. C., Oladipo, J. M., Fasolino, V., Harte, M., Mason, V., Grayson, B., McHugh, P., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.09.005 · Cited by 84 · see citing works
“In the depression field there is growing evidence to support the hypothesis that non-responders to standard medication have a pro-inflammatory profile (see (Pariante, 2017) for a recent update).”
Athira, K. V., Madhana, R. M., Indu Chandran, J. S., Lahkar, M., Sinha, S., & Naidu, V. G. M. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.009 · Cited by 81 · see citing works
“Based on the exaggerated immune response in the presence of HPA axis dysregulation induced by CORT, it may be assumed that the underlying cause to be GC resistance [48].”
BackgroundGeng, J., Liu, J., Yuan, X., Liu, W., & Guo, W. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114688 · Cited by 82 · see citing works
Zhan, Y., Zhou, Y., Zheng, W., Liu, W., Wang, C., Lan, X., Deng, X., Xu, Y., Zhang, B., & Ning, Y. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00933-z · Cited by 81 · see citing works
Rothe, N., Steffen, J., Penz, M. S., Kirschbaum, C., & Walther, A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.024 · Cited by 83 · see citing works
Faraji, N., Payami, B., Ebadpour, N., & Gorji, A. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105990 · Cited by 86 · see citing works
Gulyaeva, N. V. (2019) · Biochemistry (Moscow) · doi:10.1134/s0006297919110087 · Cited by 81 · see citing works
“Considering the accepted notion that high levels of cortisol have anti inflammatory properties, this associa tion is particularly enigmatic [38] (Fig.”
BackgroundLipidomics in Major Depressive Disorder
Walther, A., Cannistraci, C. V., Simons, K., Durán, C., Gerl, M. J., Wehrli, S., & Kirschbaum, C. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00459 · Cited by 77 · see citing works
“Although advancements in elucidating the pathophysiology of MDD have been achieved (11), one needs to acknowledge that the reductionist single biomarker approach employed during the last decades has been a failure (12).”
BackgroundChanges in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes
Xu, W., Yao, X., Zhao, F., Zhao, H., Cheng, Z., Yang, W., Cui, R., Xu, S., & Li, B. (2020) · Neural Plasticity · doi:10.1155/2020/8861903 · Cited by 73 · see citing works
Caraci, F., Calabrese, F., Molteni, R., Bartova, L., Dold, M., Leggio, G. M., Fabbri, C., Mendlewicz, J., Racagni, G., Kasper, S. F., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014977 · Cited by 73 · see citing works
Cognitive dysfunction in major depression: From assessment to novel therapies
Atique-Ur-Rehman, H., & Neill, J. C. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.05.013 · Cited by 72 · see citing works
“variants include G-174C, Banl, and COX2 rs4648308 polymorphisms in the IL-6, cytosolic phospholipase A2 and COX-2 genes respectively (Pariante, 2017).”
BackgroundThe Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases
Zhao, S., Li, X., Wang, J., & Wang, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.657478 · Cited by 71 · see citing works
“Increased inflammation is involved in the progression of depression, and the activation of NLRP3 inflammasome in microglia is an important feature of CNS inflammation under chronic stress (Pan et al., 2014; Pariante, 2017).”
BackgroundConnecting Dots between Mitochondrial Dysfunction and Depression
Khan, M., Baussan, Y., & Hébert-Chatelain, É. (2023) · Biomolecules · doi:10.3390/biom13040695 · Cited by 77 · see citing works
Caruso, G., Fresta, C. G., Grasso, M., Santangelo, R., Lazzarino, G., Lunte, S. M., & Caraci, F. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190712091515 · Cited by 74 · see citing works
The Role of Anxious Distress in Immune Dysregulation in Patients with Major Depressive Disorder
Gaspersz, R., Lamers, F., Wittenberg, G., Beekman, A. T. F., van Hemert, A. M., Schoevers, R. A., & Penninx, B. W. J. H. (2017) · Translational Psychiatry · doi:10.1038/s41398-017-0016-3 · Cited by 71 · see citing works
Steroid secretion in healthy aging
Fiacco, S., Walther, A., & Ehlert, U. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.09.035 · Cited by 71 · see citing works
Maternal depression and inflammation during pregnancy
Lahti‐Pulkkinen, M., Girchenko, P. V., Robinson, R., Lehto, S. M., Toffol, E., Heinonen, K., Reynolds, R. M., Kajantie, E., Laivuori, H. M., Villa, P., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291719001909 · Cited by 69 · see citing works
Towards Neuroecosociality: Mental Health in Adversity
Rose, N., Birk, R., & Manning, N. (2021) · Theory, Culture and Society. Explorations in Critical Social Science · doi:10.1177/0263276420981614 · Cited by 51 · see citing works
“Research does suggest pathways that do not respect the boundaries of skull and skin, and demonstrates the constitutive embeddedness of neural processes in their material milieu (Alam et al., 2017; Borsini et al., 2015; Pariante, 2017).”
Microglia and HPA axis in depression: An overview of participation and relationship
Pereira, G. C., Piton, E., dos Santos, B. M., Ramanzini, L. G., Camargo, L. F. M., da Silva, R. M., & Bochi, G. V. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1939154 · Cited by 69 · see citing works
Ghazizadeh‐Hashemi, M., Ghajar, A., Shalbafan, M., Ghazizadeh‐Hashemi, F., Afarideh, M., Malekpour, F., Ghaleiha, A., Ardebili, M. E., & Akhondzadeh, S. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.02.057 · Cited by 67 · see citing works
Gustafsson, H., Sullivan, E. L., Battison, E., Holton, K. F., Graham, A. M., Karalunas, S. L., Fair, D. A., Loftis, J. M., & Nigg, J. T. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.07.019 · Cited by 66 · see citing works
“, 2019), though it operates in conjunction with associated systems, including glucocorticoid function (Osborne et al., 2018; Pariante, 2017).”
BackgroundAmasi-Hartoonian, N., Sforzini, L., Cattaneo, A., & Pariante, C. M. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100356 · Cited by 68 · see citing works
Self-citationUnderstanding long COVID: nosology, social attitudes and stigma
Byrne, E. A. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.09.012 · Cited by 61 · see citing works
Brain-immune crosstalk in the treatment of major depressive disorder
Branchi, I., Poggini, S., Capuron, L., Benedetti, F., Poletti, S., Tamouza, R., Drexhage, H. A., Penninx, B. W. J. H., & Pariante, C. M. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.11.016 · Cited by 64 · see citing works
Self-citationNeutrophil/Lymphocyte, Platelet/Lymphocyte, and Monocyte/Lymphocyte Ratios in Mood Disorders
Marazziti, D., Torrigiani, S., Carbone, M. G., Mucci, F., Flamini, W., Ivaldi, T., & Dell'Osso, L. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867328666210922160116 · Cited by 61 · see citing works
Oudin, A., Åström, D. O., Asplund, P., Steingrímsson, S., Szabó, Z., & Carlsen, H. K. (2018) · Environmental Health · doi:10.1186/s12940-017-0348-8 · Cited by 60 · see citing works
“These recent studies suggest that air pollution exposure had acute effects while both chronic activation and inappropriate regulation of the hypothalamicpituitary-adrenal axis and inflammation were associated with worsening in depressive symptoms [36].”
BackgroundYu, H., Zhang, F., & Guan, X. (2019) · Phytotherapy Research · doi:10.1002/ptr.6340 · Cited by 59 · see citing works
“This evidence raises the possibility that inhibition of inflammation might be a potential therapeutic strategy for depression (Malek et al., 2015; Pariante, 2017).”
BackgroundHorowitz, M. A., Cattaneo, A., Cattane, N., Lopizzo, N., Tojo, L. M., Bakunina, N., Musaelyan, K., Borsini, A., Zunszain, P. A., & Pariante, C. M. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.012 · Cited by 57 · see citing works
“…in depression: raised cortisol levels and evidence of glucocorticoid resistance have been identified in depressed patients (Juruena et al., 2006; Pariante, 2017, 2009), including in metaanalysis (Stetler and Miller, 2011), as are increased levels of pro-inflammatory cytokines (Dantzer, 2018;…”
BackgroundSelf-citationLu, S.-Y., Peng, X., Dong, J.-R., Yan, H., Kong, Q., Shi, Q., Li, D., Zhou, L. M., Li, Z., & Qiu, M. (2019) · Fitoterapia · doi:10.1016/j.fitote.2019.01.013 · Cited by 56 · see citing works
Can epigenetics shine a light on the biological pathways underlying major mental disorders?
Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y., & Forti, M. D. (2022) · Psychological Medicine · doi:10.1017/s0033291721005559 · Cited by 60 · see citing works
“It is important to take into account that some of these processes participate in disease pathogenesis in a parallel manner, such as via the redox system and through the glutamatergic/GABAergic imbalance (Hardingham & Do, 2016); or the immune system and the stress response (Pariante, 2017).”
BackgroundCordeiro, R. C., Filho, A. J. M. C., Gomes, N. S., Tomaz, V. D. S., Medeiros, C. D., Queiroz, A. I. D. G., Maes, M. H. J., Macêdo, D. S., & Carvalho, A. F. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00125 · Cited by 54 · see citing works
“Peripheral immune activation and inflammation may contribute to the emergence of depression through several mechanisms including the activation of the kynurenine pathway (10), alterations in neuronal plasticity (11), microglial activation (12), and neuroendocrine effects (13).”
BackgroundBrunoni, A. R., Padberg, F., Vieira, É. L. M., Teixeira, A. L., Carvalho, A. F., Lotufo, P. A., Gattaz, W. F., & Benseñor, I. M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.06.003 · Cited by 53 · see citing works
“Although distinct, these theories are complementary since heightened stress response, observed in MDD, leads to increased activity of the hypothalamic-pituitary-adrenal axis and higher cortisol levels (Gold, 2015; Pariante, 2017) which could lead to an upregulation of pro-inflammatory cytokines accompanied by a downre…”
Disease- and treatment-associated acquired glucocorticoid resistance
Wilkinson, L., Verhoog, N. J. D., & Louw, A. (2018) · Endocrine Connections · doi:10.1530/ec-18-0421 · Cited by 54 · see citing works
Murri, M. B., Folesani, F., Zerbinati, L., Nanni, M. G., Ounalli, H., Caruso, R., & Grassi, L. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17155545 · Cited by 47 · see citing works
Ellul, P., Mariotti‐Ferrandiz, E., Leboyer, M., & Klatzmann, D. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00167 · Cited by 51 · see citing works
de Punder, K., Entringer, S., Heim, C. C., Deuter, C. E., Otte, C., Wingenfeld, K., & Kuehl, L. K. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00610 · Cited by 51 · see citing works
“Altogether, the data presented here support the hypothesis that ACEmight be a risk factor for developing aMDD later in life, and that this risk is partly mediated by increases in activation of pro-inflammatory pathways (19).”
BackgroundResultPalma‐Gudiel, H., Córdova‐Palomera, A., Tornador, C., Falcón, C., Bargalló, N., Deco, G., & Fañanás, L. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.03.015 · Cited by 50 · see citing works
Advances in the mechanisms of polysaccharides in alleviating depression and its complications
Guo, Y., Chen, X., Gong, P., Li, Z., Wu, Y., Zhang, J., Wang, J., Yao, W., Yang, W., & Chen, F. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154566 · Cited by 53 · see citing works
Chen, T., Liu, S., Zheng, M., Li, Y., & He, L. (2020) · Phytotherapy Research · doi:10.1002/ptr.6846 · Cited by 50 · see citing works
“A battery of evidence indicated that immunological dysregulation contributed to the onset of depression (Pariante, 2017).”
BackgroundNuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis
Ó’Léime, C. S., Cryan, J. F., & Nolan, Y. M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.07.153 · Cited by 50 · see citing works
Dattilo, V., Amato, R., Perrotti, N., & Gennarelli, M. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00826 · Cited by 49 · see citing works
“Vice versa, the depression resulting from post-traumatic stress such as childhood and adolescent maltreatments is associated with a strong inflammatory component in the presence of decreased levels of SGK1, accompanied by reduced hippocampal neurogenesis (Pariante, 2017).”
BackgroundWu, Q., Miao, X.-Y., Cao, Y.-Y., Chi, A.-P., & Xiao, T. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1243213 · Cited by 46 · see citing works
“Meta-analysis has indicated that an overactive hypothalamic–pituitary–adrenal axis is connected to the development of depression (64), and it can also influence the cardiovascular system of humans by modulating autonomic nerves (6).”
BackgroundLow glucocorticoids in stress-related disorders: the role of inflammation
Sarapultsev, A., Sarapultsev, P., Dremencov, E., Komelkova, M. V., Tseilikman, O. B., & Цейликман, В. Э. (2020) · Stress · doi:10.1080/10253890.2020.1766020 · Cited by 47 · see citing works
Mental health and immunity (Review)
Vasile, C. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9341 · Cited by 38 · see citing works
“The inflammatory immune response to stress, together with the link between stress and depression, shows that there is a correlation between inflam‐ mation and depression (15,16).”
BackgroundBrain–heart communication in health and diseases
Liu, W., Zhang, X., Wu, Z., Huang, K., Yang, C., & Yang, L. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.02.012 · Cited by 44 · see citing works
Persistence of learning-induced synapses depends on neurotrophic priming of glucocorticoid receptors
Arango-Lievano, M., Borie, A. M., Dromard, Y., Murat, M., Desarménien, M. G., Garabedian, M. J., & Jeanneteau, F. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903203116 · Cited by 44 · see citing works
“For example, glucocorticoid receptor insufficiency is associated with a state of low BDNF levels in diseases presenting an activated inflammatory system that is relevant for patients with major depression, schizophrenia, glucocorticoid resistance syndrome, Alzheimer’s disease (57-60).”
BackgroundSong, L., Wu, X., Wang, J., Guan, Y., Zhang, Y., Gong, M., Wang, Y., & Li, B. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.09.002 · Cited by 45 · see citing works
Clerici, L., Bottari, D., & Bottari, B. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00619-2 · Cited by 53 · see citing works
Cai, Z., Ye, T., Xu, X., Gao, M., Zhang, Y.-R., Wang, D., Gu, Y., Zhu, H., Tong, L., Lu, J., et al. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109931 · Cited by 43 · see citing works
Targeting PDK2 rescues stress-induced impaired brain energy metabolism
Wang, C., Cui, C., Xu, P., Zhu, L., Xue, H., Chen, B., & Jiang, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02098-9 · Cited by 46 · see citing works
Vagus Nerve Stimulation and Neurotrophins: a biological psychiatric perspective.
Rosso, P., Iannitelli, A., Pacitti, F., Quartini, A., Fico, E., Fiore, M., Greco, A., Ralli, M., & Tirassa, P. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.034 · Cited by 36 · see citing works
- 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 › Treatment of Major Depression
- Keywords
- major depressive disorder, inflammation, glucocorticoid resistance, hypothalamic-pituitary-adrenal axis, hypercortisolism, cortisol, depression pathogenesis, depression treatment
- MeSH terms
- Anti-Inflammatory Agents, Depression, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Inflammation, Metabolism, Inborn Errors, Pituitary-Adrenal System, Receptors, Glucocorticoid, Time Factors, Inflammation Mediators, Biomedical Research
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
