Jennifer C Felger

Emory University | EU · Department of Psychiatry and Behavioral Sciences

Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopa...

Depression is associated with alterations in corticostriatal reward circuitry. One pathophysiologic pathway that may drive these changes is inflammation. Biomarkers of inflammation (e.g. cytokines and C-reactive protein [CRP]) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and d...

Studies using neuroimaging and in vivo microdialysis in humans and nonhuman primates indicate that inflammatory cytokines such as interferon-alpha reduce dopamine release in the ventral striatum in association with depressive symptoms including anhedonia and psychomotor slowing. Herein, we examined whether reduced striatal dopamine release in rhesu...

Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal...

Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavi...

Chronic inflammation has been implicated in the pathophysiology of major depressive disorder (MDD). Activating the resolution of inflammation through ω-3 fatty acid supplementation may prove to be a successful therapeutic strategy for the treatment of MDD. Patients with MDD, body mass index >25 kg/m2, and plasma high-sensitivity C-reactive protein...

Findings from numerous laboratories and across neuroimaging modalities have consistently shown that exogenous administration of cytokines or inflammatory stimuli that induce cytokines disrupt circuits and networks involved in motivation and motor activity, threat detection, anxiety, interoceptive and emotional processing. While inflammatory effects...

Increased inflammation in major depressive disorder (MDD) has been associated with low functional connectivity (FC) in corticostriatal reward circuits and symptoms of anhedonia, relationships which may involve the impact of inflammation on synthesis and release of dopamine. To test this hypothesis while establishing a platform to examine target eng...

Posttraumatic stress disorder (PTSD) develops in a subset of individuals upon exposure to traumatic stress. In addition to well-defined psychological and behavioral symptoms, some individuals with PTSD also exhibit elevated concentrations of inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Moreover, PT...

Inflammatory stimuli have been shown to impact brain regions involved in threat detection and emotional processing including amygdala and ventromedial prefrontal cortex (vmPFC), and to increase anxiety. Biomarkers of endogenous inflammation, including inflammatory cytokines and C-reactive protein (CRP), are reliably elevated in a subset of patients...

Introduction Sleep disturbance is a prominent concern in patients with cancer with detrimental effect on health outcomes. Although inflammation has been proposed as a potential mechanism of sleep disturbance, there is a dearth of longitudinal data supporting the relationship between cancer-related sleep disturbance and inflammatory markers. The goa...

Inflammation is associated with symptoms of anhedonia, a core feature of major depression (MD). We have shown that MD patients with high inflammation as measured by plasma C-reactive protein (CRP) and anhedonia display gene signatures of metabolic reprograming (e.g., shift to glycolysis) necessary to sustain cellular immune activation. To gain prel...

Anhedonia, characterized by a lack of motivation, interest, or ability to experience pleasure, is a prominent symptom of depression and other psychiatric disorders and has been associated with poor response to standard therapies. One pathophysiologic pathway receiving increased attention for its potential role in anhedonia is inflammation and its e...

Inflammation impacts basal ganglia motor circuitry in association with psychomotor retardation, a key symptom of major depression (MD). We previously reported associations between circulating protein inflammatory biomarkers and psychomotor slowing as measured by neuropsychological tests probing psychomotor speed in patients with MD. To discover nov...

Inflammation is associated with the development of anhedonia in major depression (MD), but the pathway by which inflammatory molecules gain access to the brain and lead to anhedonia is not clear. Molecules of the kynurenine pathway (KP), which is activated by inflammation, readily influx into the brain and generate end products that alter brain che...

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflamma...

Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately anhedonia, a core and disabling symptom of depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems and neurocircuits in subcortica...

Inflammation is associated with depressive symptoms including anhedonia in patients with major depression. Nevertheless, the mechanisms by which peripheral inflammatory signals are communicated to the brain to influence central nervous system (CNS) function has yet to be fully elucidated. Based on laboratory animal studies, molecules of the kynuren...

Background: The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with cancer. Methods: Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12...

Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symp...

Bidirectional relationships between inflammation and metabolic dysfunction may contribute to the pathophysiology of psychiatric illnesses like depression. Metabolic disturbances drive inflammation, which in turn exacerbate metabolic outcomes including insulin resistance. Both inflammatory (e.g. endotoxin, vaccination) and metabolic challenges (e.g....

Background IFN-α-induced depression in patients undergoing hepatitis C virus (HCV) treatment provides powerful support for the inflammation hypothesis of depression. Most studies have focused on the occurrence of depressive symptoms, but there has been no study yet in depression-free HCV patients receiving IFN-α. We hypothesized that HCV patients w...

Trauma exposure is associated with increased inflammatory biomarkers (e.g. C-reactive protein [CRP] and cytokines), and inflammation has been shown to impact corticostriatal reward circuitry and increase anhedonia-related symptoms. We examined resting-state functional MRI in a high-trauma inner-city population of African-American women (n = 56), wh...

Patients with schizophrenia exhibit psychomotor deficits that are associated with poor functional outcomes. One pathway that may be associated with psychomotor slowing is inflammation. Inflammatory markers have been shown to be elevated in patients with schizophrenia and are associated with psychomotor deficits in both animal and human studies. For...

Objective: Fatigued cancer patients often have high peripheral inflammation; however, the biological mechanisms of this association remain unclear. We examined whether decreased sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids may contribute to inflammation and fatigue in head and neck cancer (HNC) patients during tr...

Inflammation and altered glucose metabolism are two pathways implicated in the pathophysiology of major depressive disorder (MDD). We have previously shown that high inflammation as measured by C-reactive protein (CRP) in MDD patients is associated with symptoms of anhedonia, a core symptom of MDD, along with deficits in dopaminergic reward circuit...

Kynurenine pathway (KP) metabolites are believed to be a link between inflammation and depression through effects on brain glutamate receptors. However, neither the relationship between plasma and cerebrospinal fluid (CSF) KP metabolites nor their association with inflammatory mediators is well-established in depression. Moreover, the clinical prof...

Major depressive disorder is a heterogeneous disease involving widespread disruptions in functional brain networks, the neurobiological mechanisms of which are poorly understood. Amassing evidence supports innate immune activation as one pathophysiologic mechanism contributing to depression in a subgroup of patients with elevated inflammatory marke...

Approximately one third of depressed patients fail to respond to currently available antidepressant therapies. Therefore, new conceptual frameworks are needed to identify pathophysiologic pathways and neurobiological targets for the development of novel treatment strategies. In this regard, recent evidence suggests that inflammation may contribute...

Combined increases in peripheral inflammation and brain glutamate may identify a subtype of depression with distinct neuroimaging signatures. Two contrasting subgroups of depressed subjects—with and without combined elevations in plasma C-reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu, respectively) were identified by hier...

The tumor necrosis factor (TNF) antagonist infliximab was previously found to reduce depressive symptoms in patients with treatment-resistant major depression (TRD) who exhibited high baseline inflammation, as reflected by plasma C-reactive protein (CRP) >5 mg/L. Further predictors of antidepressant response to infliximab included differential expr...

Biomarkers of inflammation, including inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), are reliably increased in a subset of patients with depression, anxiety disorders and post-traumatic stress disorder (PTSD). Administration of innate immune stimuli to laboratory subjects and the associated release of inflammatory cyt...

Background: One third of patients with major depressive disorder (MDD) fail to respond to currently available antidepressant medications. Inflammation may contribute to treatment non-response through effects on neurotransmitter systems relevant to antidepressant efficacy. In post-hoc analyses, increased concentrations of inflammatory markers prior...

BACKGROUND Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influence...

Background Psychosocial and inflammatory factors have been associated with fatigue in breast cancer survivors. Nevertheless, the relative contribution and/or interaction of these factors with cancer-related fatigue have not been well documented. Method This cross-sectional study enrolled 111 stage 0–III breast cancer patients treated with breast s...

Advances in our understanding of immunology especially cellular immunology and cytokine biology have led to monumental changes in the practice of medicine. Indeed, elucidation of the pathways involved in T-cell regulation have led to a series of therapeutic agents referred to as ‘checkpoint inhibitors’ that are revolutionizing the treatment of canc...

The purpose of this study was to examine predictors of fatigue in breast cancer survivors one-year post-radiotherapy. This cross-sectional, observational study enrolled 111 patients treated with breast conserving surgery followed by whole breast radiotherapy. Half of the patients received chemotherapy. The primary outcome variable was fatigue, meas...

A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specifi...

Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal r...

Previous data have demonstrated that administration of inflammatory cytokines or their inducers leads to altered basal ganglia function associated with reduced psychomotor speed. Decreased psychomotor speed, referred to clinically as psychomotor retardation, is a cardinal symptom of major depressive disorder (MDD) and has been associated with poor...

Purpose/objective: The purpose of this study was to examine the impact of radiotherapy on quality of life (QOL) of breast cancer patients during and until 1 year post radiotherapy treatment. Methods and materials: Thirty-nine breast cancer patients treated with breast conserving surgery were enrolled in a prospective study prior to whole breast...

Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC)...

Major medical illnesses are associated with increased risk for depression and alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Pathophysiological processes such as inflammation that occur as a part of medical illnesses and their treatments have been shown to cause depressive symptoms, and may also affect the HPA axis. We previousl...

Patients with head and neck cancer (HNC) receiving intensity-modulated radiation therapy (IMRT) have particularly high rates of fatigue, and pre- and post-radiotherapy fatigue are prognostic factors for pathologic tumor responses and poor survival. Although inflammation has been proposed as one of the potential mechanisms of fatigue in cancer patie...

This study assessed changes in gene expression and their association with fatigue in head and neck cancer (HNC) patients receiving Intensity-Modulated Radiotherapy (IMRT). Consented patients were investigated pre- and 1-month post-IMRT. Fatigue was assessed by Multidimensional Fatigue Inventory-20. RNA was isolated from peripheral blood mononuclear...

Neuroimaging studies indicate that inflammatory cytokines decrease activation of the ventral striatum in association with increased symptoms of anhedonia. Our in vivo microdialysis studies in non-human primates suggest that these effects are mediated by decreased striatal dopamine synthesis and release, which can be reversed by administration of th...

Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on gluta-mate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing gluta-mate release. Increased glutamate has also been fo...

Data indicate a compelling relationship between inflammation and depression that may have profound clinical relevance (1). A significant proportion of patients with depression reliably exhibit increased inflammatory markers, and exposure of humans to stress, a well-known precipitant of depression, is associated with activation of inflammatory respo...

This pilot study examined whether breast cancer patients with childhood trauma exhibit increased fatigue, depression, and stress in association with inflammation as a result of whole breast radiotherapy (RT). Twenty breast cancer patients were enrolled in a prospective, longitudinal study of fatigue, depression, and perceived stress prior to RT, we...

Blockade of the inflammatory cytokine tumor necrosis factor (TNF) in depressed patients with increased inflammation has been associated with decreased depressive symptoms. Nevertheless, the impact of TNF blockade on sleep in depressed patients has not been examined. Accordingly, sleep parameters were measured using polysomnography in 36 patients wi...

Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate metabolism by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been fo...

Background / Purpose: There has been increasing interest in the role of inflammation and inflammatory cytokines in depression, and recent neuroimaging data from our group and others suggest that inflammatory cytokines target the basal ganglia to contribute to depressive symptoms. These findings have included cytokine and inflammation-induced decr...

Inflammation has been associated with fatigue during and after various types of breast cancer treatments. We examined whether prior chemotherapy was associated with DNA methylation patterns that could explain persisting inflammation and/or fatigue in women treated for breast cancer. Prior to breast radiation therapy, DNA was extracted from peripher...

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Highlight •Pilger et al. report a relationship between affective, neuroendocrine and inflammatory responses to stress in orchestra musicians during stage performance.