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Inflammatory cytokines in depression: Neurobiological mechanisms and therapeutic implications
Open accessAbstract
Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, such as brain-derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression's development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed.
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TL;DR
This review argues that inflammatory cytokines contribute to a subtype of depression by altering neurotransmitter, neuropeptide, growth-factor, and glutamate systems, with evidence drawn from human and animal studies. It proposes that cytokine-related depression may be identified through inflammatory biomarkers and genetic variants and treated by targeting inflammation or its downstream neural effects.
Key findings
- Elevated proinflammatory cytokines and markers—including IL-1, IL-6, TNF-alpha, CRP, and PGE2—are reported in idiopathic major depression and in medically ill populations; cancer patients show elevated cytokines and depression/fatigue rates approaching 50%, and IFN-alpha treatment induces depression in 30–50% of patients depending on dose.
- Peripheral cytokines can reach the brain through circumventricular organs, active transport, vagal afferents, endothelial/perivascular activation, and immune-cell recruitment, then amplify local inflammatory signaling involving COX-2/PGE2, microglia, IDO/KYN metabolites, iNOS, and reactive oxygen/nitrogen species.
- Specific polymorphisms are linked to particular symptom dimensions: IL-6 rs1800795 with depression but not worsening fatigue during IFN-alpha therapy; TNF-alpha A-308G rs1800629 with irritable anger rather than depression; 5-HTTLPR with neurovegetative symptoms; BDNF Met with more psychological/cognitive symptoms; and IDO1 rs9657182 with IFN-alpha-induced depression in Caucasian C-risk-allele carriers but not African Americans.
- Therapeutic implications include SSRIs being more effective for mood, anxiety, and cognitive symptoms than for fatigue/neurovegetative symptoms; the TNF antagonist infliximab improved depressive symptoms in treatment-resistant patients only when baseline CRP was high (hsCRP >5 mg/L); other candidates include COX inhibitors, omega-3 fatty acids, p38 MAPK/NF-kB inhibitors, BH4/monoamine-synthesis support, IDO/KYN inhibitors, and NMDA antagonists.
Methods
- Narrative review synthesizing human clinical studies—including idiopathic major depression, medically ill populations, IFN-alpha-treated patients, CSF and blood biomarker studies, neuroimaging, and genetic association studies—alongside animal and preclinical mechanistic work.
- The paper integrates evidence across proposed pathways: cytokine access to the brain, monoamine and glutamate neurotransmission, BDNF, CRH/HPA-axis function, and inflammatory signaling.
- Main analysis is qualitative synthesis; no systematic search strategy, meta-analysis, or formal risk-of-bias assessment is described.
Limitations
- The paper states that much of the vulnerability and treatment literature relies on correlative relationships among SNPs, inflammatory or neurotransmitter biomarkers, and behavioral symptoms, so mechanistic animal/translational studies and subsequent clinical trials are needed.
- The paper also states that more human neuroimaging is needed, that peripheral transcriptomic findings should be integrated with brain imaging, and that many studies did not examine biomarkers or polymorphisms in relation to specific depressive symptom dimensions.
- Evident from the text: as a narrative review, it lacks a systematic search and inclusion process, and many cited findings come from specific populations or preclinical models, which may limit generalizability.
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105 Not checked yet · 24 Own interpretation · 2 Own method · 2 No basis given
In the paper
“Nonetheless, it is biologically plausible that inflammatory cytokines serve as mediators of both environmental and genetic factors that may trigger the development of depressive disorders (Raison and Miller, 2011).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
- Not checked yetcites Raison and Miller, 2011 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“However, under conditions of chronic exposure to elevated inflammatory cytokines, persistent alterations in neurotransmitter function and behavior can lead to the development neuropsychiatric dysfunction, and especially depression.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, administration of cytokines to humans and laboratory animals produces neuropsychiatric symptoms and behavioral alterations consistent with depression (Miller et al., 2009).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
- Not checked yetcites Miller et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > Abstract
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In the paper
“Cytokines also have the capability of influencing neurocircuitry and neurotransmitter systems to produce behavioral alterations (Miller et al., 2009, Haroon et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Numerous studies have reported increases in circulating proinflammatory cytokines, interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-alpha, their soluble receptors, and the acute phase protein, C-reactive protein (CRP), in patients with idiopathic major depression (Maes et al., 1992, Maes, 1999, Sluzewska, 1999).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.1 Elevated cytokines and inflammatory markers in idiopathic major depression
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Therefore, depression that is associated with inflammatory cytokines may be one subtype of depression.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Acutely, administration of cytokines or activation of the innate immune system can induce a behavioral repertoire termed “sickness behavior” that includes anhedonia, anorexia, fever, sleep changes, and decreased social interaction (Dunn and Swiergiel, 1998, Dunn et al., 2005, Dantzer and Kelley, 2007).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“some patients with idiopathic major depression without co-morbid medical illness also exhibit increased circulating cytokines and inflammatory markers (Maes et al., 1992, Maes, 1999, Sluzewska, 1999, Dowlati et al., 2010).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, it is worthy to note that one study observed no association between the development of IFN-alpha-induced depression and polymorphic regions examined in the genes encoding TNF (rs1799964, rs1800629, rs3093662, rs769178), IL6 (rs1800795, rs1800796, rs1800797), IL1A (rs3783516, rs3783546), IL1B (rs1143643, rs1143644, rs16944, rs4848306), chemokine MCP-1/CCL2 (rs1024611, rs2530797,rs4586), or”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
- Not checked yetcites Smith et al., 2012 source
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 3
- It may state two separate claims as one. 53
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
“We should note that not all types of depression necessarily involve cytokines, e.g. post-partum and peri-menopausal depression, hypothyroidism, depression secondary to cocaine withdrawal, and vascular depression to name just a few.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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In the paper
“That is, not all subjects exhibiting increased inflammatory cytokines develop depression, and there are numerous vulnerability and resilience factors for cytokine-induced depression (Kendler et al., 2001, Caspi et al., 2003, Duman and Monteggia, 2006, Heim et al., 2008, Lotrich, 2011)”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
What the sources say
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Factors that may precipitate inflammation and influence the development of depression include medical illness, obesity, psychosocial stress, sleep disturbance, and gastrointestinal inflammation, and will be discussed herein.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 1. Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Interestingly, all of these pathways have been demonstrated to be affected by inflammatory cytokines (Pace et al., 2007, Dantzer et al., 2008, Miller et al., 2009, Haroon et al., 2012) (Figure 1).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistent with the relationship between circulating IL-6 and IFN-alpha-induced depression, a functional polymorphisms in the promoter region of the IL-6 gene (rs1800795), the genotype that produces more IL-6, was found to be associated with depression but not the fatigue that worsens during IFN-alpha therapy (Bull et al., 2008).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
- Not checked yetcites Bull et al., 2008
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, cancer patients exhibit elevated circulating proinflammatory cytokines and develop depression and fatigue at rates approaching 50% (Musselman et al., 2001b, Massie, 2004, Jehn et al., 2006).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.2 Medical illness and depression
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“IFN-alpha is notorious for producing behavioral symptoms including fatigue and neurovegetative symptoms, cognitive and sleep changes, anxiety, and anhedonia, and induces depression in 30–50% of treated-patients depending on the dose (Capuron et al., 2002, Maddock et al., 2005, Raison et al., 2005a, Lotrich, 2009).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.5 Exogenous cytokine administration and depression
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, omega-3 fatty acids are reduced in major depression and also predict vulnerability to cytokine-induced depression (Su et al., 2010, Lotrich et al., 2012, McNamara and Lotrich, 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
- Not checked yetcites Su et al., 2010
- Not checked yetcites Lotrich et al., 2012
- Not checked yetcites McNamara and Lotrich, 2012
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, DAMPS and the NLRP3 inflammasome may serve as a primary link by which chronic psychological or physical stress is translated into damage signals that promote inflammatory activity, and may contribute to depression as well as associated co-morbid medical illnesses related to chronic stress (Iwata et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.3 Sources of cytokines and inflammation in medically healthy individuals
What the sources say
- Not checked yetcites Iwata et al., 2012
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Inflammatory cytokine administration and low-grade chronic inflammation have been shown to increase IDO activity and the metabolisms of tryptophan, the primary amino-acid precursor of serotonin, to KYN in the periphery (Capuron et al., 2003a, Raison et al., 2010b, Capuron et al., 2011a).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Capuron et al., 2003a
- Not checked yetcites Raison et al., 2010b
- Not checked yetcites Capuron et al., 2011a
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, obesity is associated with increased circulating cytokines, and BMI significantly influences concentrations of L-6 and other inflammatory markers (Khaodhiar et al., 2004).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.3 Sources of cytokines and inflammation in medically healthy individuals
What the sources say
- Not checked yetcites Khaodhiar et al., 2004 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, selective serotonin (5-HT) reuptake inhibitors (SSRIs) have been shown to alleviate cytokine-induced depression (Musselman et al., 2001a, Raison et al., 2007), and depressive and anxiety symptoms appear to be most responsive, while fatigue and neurovegetative symptoms are less responsive (Capuron et al., 2002, Raison et al., 2005b, McNutt et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the brain, IDO activity is significantly increased at 24 hr and peaks at 48 hr in response to LPS administration, corresponding to the expression of some depressive-like behaviors, e.g. increased immobility in the forced-swim and tail suspension tests, in laboratory animals (Lestage et al., 2002, O'Connor et al., 2008).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Lestage et al., 2002 source
- Not checked yetcites O'Connor et al., 2008
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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 finding suggest that neuroactive KYN metabolites, KA and QUIN, are likely responsible for many behavioral changes associated with cytokine-induced IDO activity, and may involve effects on other neurotransmitter systems (see Section 3.3 for discussion).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, inflammatory cytokines, including IL-6, have been shown to increase 5-HTT expression and function (Morikawa et al., 1998, Mossner et al., 1998, Sakai et al., 2003, Tsao et al., 2008) (see Figure 1), an effect found to be mediated by induction of p38 mitogen-activated protein kinase (MAPK), both in vitro and in vivo (Zhu et al., 2005, Zhu et al., 2006, Zhu et al., 2010a).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In terms of immunologic mechanisms of IFN-alpha-induced depression, IFN-alpha may act directly on the central nervous system (CNS), but may also exert indirect effects via the activation of other peripheral and central inflammatory cytokines (Raison et al., 2009).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.5 Exogenous cytokine administration and depression
What the sources say
- Not checked yetcites Raison et al., 2009 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, a polymorphism (rs9657182) in the promoter region of the gene encoding IDO1 was found to be associated with IFN-alpha-induced depression in Caucasian subjects homozygous for the C risk allele, but not African Americans who exhibited a markedly lower frequency of the risk allele at this locus (Smith et al., 2012)(see Table 1 for details).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
- Not checked yetcites Smith et al., 2012 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These metabolites can then interact with neurotransmitter systems in the brain, particularly glutamate (see Section 3.3), and are thought to be involved in the behavioral effects of cytokines (Dantzer et al., 2011, Haroon et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
What the sources say
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In patients treated chronically with IFN-alpha for hepatitis C virus (HCV), CSF concentrations of IL-6 negatively correlated with 5-HIAA concentrations, which in turn negatively correlated with IFN-alpha-induced depression severity (Raison et al., 2009).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Raison et al., 2009 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Cytokines released by peripheral immune cells or adipose tissue can access the CNS to initiate local immune activation by several mechanisms, including 1.) passage through leaky regions in the blood-brain-barrier at circumventricular organs”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.4 Access of peripheral cytokines to the brain and activation of local inflammatory networks
What the sources say
- Not checked yetcites Katsuura et al., 1990
- Not checked yetcites Banks et al., 1995 source
- Not checked yetcites Bluthe et al., 1994
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Another source of inflammatory cytokines is the gut, and there has been attention paid to the role of intestinal microorganisms in influencing the immune responses of an organism (Lee and Mazmanian, 2010).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.3 Sources of cytokines and inflammation in medically healthy individuals
What the sources say
- Not checked yetcites Lee and Mazmanian, 2010
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Therefore, differential responsiveness of symptom dimensions coupled with the association of specific gene loci with behavioral symptoms suggests that distinct mechanisms may mediate the various aspects of cytokine-induced depression, and understanding these mechanisms may improve treatment strategies.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 2. Cytokines and depression > 2.6 Genetic vulnerability to exogenous cytokine-induced depression
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, it is reasonable that HPA-mediated vulnerability to cytokine-induced depression represents a more general hyper-responsiveness and pre-existing vulnerability to stress or inflammatory challenge, which may be mediated by changes in glucocorticoid receptor (GR) expression or function (Pace et al., 2007).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.2 Cytokine effects on neuropeptides and growth factors
What the sources say
- Not checked yetcites Pace et al., 2007 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Inflammatory cytokines activate IDO and KYN pathways in the brain that effect glutamate neurotransmission and may contribute to glutamate dysfunction in depression (McNally et al., 2008, Dantzer et al., 2011, Haroon et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Increased uptake and decreased turnover of FDOPA suggests a potential depletion of DA in DAergic terminals and increased synthetic capacity following IFN-alpha exposure.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
hedgedconditional- 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
“Acutely, cytokines and immune activation increase locus coeruleus activity and NE release in the hippocampus and hypothalamus. This increase in NE activity is relevant to HPA-axis activation, fever, and metabolic change associated with immune activation (Dunn et al., 1999, Dunn et al., 2005).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although inflammatory cytokines have been shown to induce GTP-cyclohydrolase I, the enzyme necessary for BH4 synthesis, inflammation-mediated. increases in ROS/RNS can oxidize BH4, whereas increased inducible NOS (iNOS) activity can usurp BH4 (see Figure 1), thus reducing it’s availability for DA synthesis (Cunnington and Channon, 2010).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Cunnington and Channon, 2010
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
“Monkeys that display huddling behavior in response to IFN-alpha have been found to exhibit significantly lower CSF concentrations of the dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) (Felger et al., 2007, Felger and Miller, 2012), which correlated with reduced locomotor activity (Felger and Miller, 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Felger et al., 2007 source
- Not checked yetcites Felger and Miller, 2012
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
“Rhesus monkeys that express functional IFNARs and activate relevant signal transduction pathways in response to human IFN-alpha (Felger et al., 2007), exhibit immune, neuroendocrine, and behavioral responses to IFN-alpha similar to humans, including decreases in psychomotor activity and increases in depressive-like huddling behavior (in ~50% of animals) (Felger et al., 2007, Felger and Miller, 201”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Felger et al., 2007 source
- Not checked yetcites Felger and Miller, 2012
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
“Plasma Phen/Tyr ratios were increased in IFN-alpha-treated subjects compared to controls (Felger et al., 2012b, Zoller et al., 2012), and negatively correlated with CSF concentrations of DA and HVA, and positively correlated with fatigue, in IFN-alpha-treated patients (Felger et al., 2012b).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Felger et al., 2012b
- Not checked yetcites Zoller et al., 2012 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
“Furthermore, CSF concentrations of BH2 were significantly increased in IFN-alpha-treated patients compared to controls, and decreased CSF BH4 concentrations correlated with increased CSF IL-6 (Felger et al., 2012b).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Felger et al., 2012b
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
“Interestingly, both increased uptake and decreased turnover of FDOPA in the caudate, putamen and ventral striatum of IFN-alpha-treated patients was found (Capuron et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
- Not checked yetcites Capuron et al., 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both KA and QUIN have been observed to be increased in the CSF of IFN-alpha-treated patients (Schwarcz and Pellicciari, 2002, Raison et al., 2010b), and CSF QUIN correlated with depressive symptoms during IFN-alpha administration (Raison et al., 2010b).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
- Not checked yetcites Schwarcz and Pellicciari, 2002
- Not checked yetcites Raison et al., 2010b
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
“IFN-alpha administration has also been found to decrease systemic BDNF levels in humans (Kenis et al., 2010, Lotrich et al., 2013) (see Figure 1), as can other inflammatory cytokines and LPS injections (Tong et al., 2008, Cortese et al., 2011) (Guan and Fang, 2006).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.2 Cytokine effects on neuropeptides and growth factors
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Inflammatory cytokines have repeatedly been observed to influence both neuronal development and apoptosis (Chawla-Sarkar et al., 2003, Hayley et al., 2005) (Mehler and Kessler, 1997, Zhao and Schwartz, 1998), (Peng et al., 2008, Anisman, 2009, Koo et al., 2010b). In fact, both stress and subsequent inflammatory cytokine activity may adversely influence neurogenesis and neuroplasticity (Patel et al”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.2 Cytokine effects on neuropeptides and growth factors
What the sources say
hedgedconditional- 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 terms of the role of 5-HT in the treatment of cytokine-induced depression, SSRIs have been very effective in treating anxiety, depressed mood, and cognitive aspects of cytokine-induce depression, but not as effective for fatigue and neurovegetative symptoms (Capuron et al., 2002, Raison et al., 2005b, McNutt et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It is noteworthy that a direct comparison of the 5-HTTLPR and the met/val allele of BDNF found that the 5-HTTLPR Short allele was specifically associated with risk for neurovegetative symptoms of depression, while the BDNF Met allele was primarily associated with the cognitive symptoms (Lotrich et al., 2013).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.2 Cytokine effects on neuropeptides and growth factors
What the sources say
- Not checked yetcites Lotrich 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.
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
“Taken together, these data suggest that peripheral cytokine effects on basal ganglia function generalize to multiple inflammatory stimuli, and may be relevant to depression and specifically to symptoms of fatigue and psychomotor slowing.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
hedgedconditional- 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
“The fatigue of depression, which is often a residual symptom of SSRI therapy, is a prominent feature of cytokine-induced depression, and may represent cytokine effects on the basal ganglia and dopamine (DA) function (Capuron et al., 2001, Majer et al., 2008, Capuron et al., 2009).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 results indicate that inflammation is associated with decreased peripheral conversion of Phen to Tyr, which may in turn be associated with reduced DA in the brain as well as behavioral symptoms such as anhedonia and fatigue.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
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.
None of the sources cited for this claim have been checked yet.
In the paper
“MHPG has been examined in the CSF of IFN-alpha-treated patients but was not related to behavioral symptoms (Raison et al., 2009). SNPs of the gene for DA beta-hydroxylase, the enzyme that converts DA to NE, was examined in IFN-alpha-treated HCV+ subjects but was not associated with the development of depression (Smith et al., 2012).”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.1 Cytokine effects on the monoamines
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“baseline concentrations of circulating cytokines, such as IL-6, and markers of inflammation, like CRP, may be useful for indentifying subjects that will fail to respond to current antidepressant therapies”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.1 Clinical significance and limitations
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.
None of the sources cited for this claim have been checked yet.
In the paper
“QUIN has been implicated in a number of neurodegenerative diseases, including Huntington’s disease, Amyotrophic Lateral Sclerosis, Alzheimer’s disease, and dementia secondary to infection with HIV”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
- Not checked yetcites Schwarcz and Pellicciari, 2002
- Not checked yetcites Guidetti and Schwarcz, 2003
- Not checked yetcites Guillemin et al., 2005a
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the mRNA specific adenosine deaminase 1 (ADAR1), which edits the AMPA glutamate receptor, is strongly induced by IFN-alpha”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
- Not checked yetcites Liu and Samuel, 1999
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“persons with a history of childhood trauma tend to have higher inflammatory biomarkers as adults and also exhibit higher rates of depression”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.1 Clinical significance and limitations
What the sources say
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
“QUIN and inflammatory cytokines have also been shown to increase glutamate release and decrease the astrocytic uptake of glutamate by the excitatory amino acid transporter”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Thus there are a variety of routes by which cytokines may influence the glutamatergic system and conceivably increase risk for depression.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
hedgedconditional- 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
“thus making glutamate more available to extrasynaptic NMDARs and contributing to glutamate toxicity”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 3. Cytokine effects on neurotransmitter systems that may contribute to depression > 3.3 Cytokine effects on glutamate neurotransmission
What the sources say
- Not checked yetcites Hardingham et al., 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Parkinson’s-like symptoms have been observed in some patients during IFN-alpha administration, and these symptoms have been successfully treated with levodopa”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.2 Potential therapeutic strategies for treatment of cytokine-induced depression
What the sources say
- Not checked yetcites Mizoi et al., 1997
- Not checked yetcites Sarasombath et al., 2002
- Not checked yetcites Bersano et al., 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“numerous biomarkers and gene polymorphisms that confer vulnerability to cytokine-induced depression have been indentified, and may be useful in identifying at-risk patients”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 5. Summary and conclusions
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
“IDO-deficient mice are resistant to behavioral changes following infection with bacille Calmette–Guerin (BCG), while showing a normal inflammatory cytokine response to BCG administration”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.2 Potential therapeutic strategies for treatment of cytokine-induced depression
What the sources say
- Not checked yetcites O'Connor et al., 2009a
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
“low serum folate has been associated with depression and with resistance to antidepressant treatment”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.2 Potential therapeutic strategies for treatment of cytokine-induced depression
What the sources say
- Not checked yetcites Fava et al., 1997 source
- Not checked yetcites Papakostas et al., 2004a
- Not checked yetcites Gilbody et al., 2007a
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“inhibition of the NMDA receptor with memantine prevented the onset of DA deficits in the brains of SIV-infected macaques, and effect mediated by increased BDNF”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.2 Potential therapeutic strategies for treatment of cytokine-induced depression
What the sources say
- Not checked yetcites Meisner et al., 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Sapropterin (Kuvan) is the first non-dietary, FDA-approved, synthetic form of BH4 for patients with phenylketonuria that is effective in lowering blood Phen levels by stabilizing and increasing PAH activity”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 4. Translational and therapeutic implications > 4.2 Potential therapeutic strategies for treatment of cytokine-induced depression
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Peripheral cytokines can access the brain and activate local CNS inflammatory networks to produce alterations in neurotransmitter function.”
§ Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications > 5. Summary and conclusions
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.
The paper relies on this without support.
SSRIs and other classical antidepressants targeting the 5-HT system are efficacious for many aspects of major depression and cytokine-induced depression.
“Although SRRIs and other classical antidepressants that target the 5-HT system are efficacious in treating many aspects of both major depression and cytokine-induced depression”
The paper relies on this without support.
Knockout mice lacking the ATP P2X7 receptor, which stimulates inflammasome-mediated IL-1beta release, show an antidepressant-like profile with increased mobility in tail suspension and forced swim tests.
“knockout mice for the ATP P2X7 receptor that stimulates inflammasome-mediated IL-1beta release exhibit an antidepressant-like profile, including increased mobility in the tail suspension and forced swim tests”
The paper relies on this without support.
Classic stimulants increase dopamine release and block DAT function.
“Classic stimulants act to increase DA release and block DAT function”
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
“Secretion of IL-1β, IL-6 and TNF-α with macrophage-associated proinflammatory cytokines was synchronized with M1 activation in MDD patients [15].”
From Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression (2022) · cites this paper as [15]
Experimental — accuracy not yet measuredIn the citing paper
“It has been shown that chronic exposure to elevated inflammatory cytokines can lead to depression (108).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [108]
In the citing paper
“Growing evidence suggests that pro-inflammatory cytokines contribute to the pathogenesis of psychiatric diseases such as depression [137,138]”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [137]
In the citing paper
“The idea that stress itself induces endocrine mediators like IL6, which is traditionally associated with inflammation, has since been supported by the detection of increased circulating cytokines in depression and anxiety (Felger and Lotrich, 2013; Khandaker et al., 2014), and by the association of IL6 polymorphisms in individuals with depression (Zhang et al., 2016).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Felger and Lotrich, 2013
Citations
Cites
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How Stress Induces Intestinal Hypersensitivity
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Metadata
- Authors
- Felger, J. C., & Lotrich, F. E.
- Affiliations
- Emory University (US)
- University of Pittsburgh (US)
- ORCID
- Felger, J.C.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 246
- Pages
- 199-229
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3741070
- OpenAlex
- W2004243143
- Cited by
- 1,180
- References
- 445
- Citations by year
- 2026: 97 · 2025: 125 · 2024: 99 · 2023: 98 · 2022: 127 · 2021: 107 · 2020: 86 · 2019: 104 · 2018: 101 · 2017: 70 · 2016: 60 · 2015: 61 · 2014: 31 · 2013: 12
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIMH (R090250)
- the Glenn Family Breast Fund
- the Winship Cancer Institute
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- inflammatory cytokines, depression, neuroinflammation, innate immune system, monoaminergic systems, glutamatergic system, neuropeptides, brain-derived neurotrophic factor, genetic polymorphism, childhood trauma, obesity, stress, sleep, neurotransmitter systems, cytokine signaling, anti-inflammatory therapy
- MeSH terms
- Animals, Antidepressive Agents, Brain, Depression, Humans, Inflammation, Biomarkers, Cytokines, Inflammation Mediators
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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.
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