a School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA b School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Usona Institute, Fitchburg, WI, USA d Departments of Psychiatry,... more
a School of Human Ecology, University of Wisconsin-Madison, Madison, WI, USA b School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA Usona Institute, Fitchburg, WI, USA d Departments of Psychiatry, Medicine, and Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA e Stress, Psychiatry and Immunology Lab, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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While oncology clinical research coordinators (CRCs) experience a combination of factors that are thought to put them at increased risk for burnout, very little research has been conducted to understand the risk factors associated with... more
While oncology clinical research coordinators (CRCs) experience a combination of factors that are thought to put them at increased risk for burnout, very little research has been conducted to understand the risk factors associated with burnout among CRCs. We used a mixed-method approach, including self-report questionnaires to assess burnout and compassion satisfaction, as well as individual and interpersonal variables hypothesized to impact CRC well-being. We also conducted a focus group to gain a more nuanced understanding of coordinators’ experiences around burnout, teamwork, resilience, and incivility. Coordinators reported relatively moderate levels of burnout and compassion satisfaction. Resilience, sleep dysfunction, stress, and incivility experienced from patients/family were significant predictors of burnout. Resilience and incivility from patients/family were significant predictors of compassion satisfaction. Themes that emerged from the focus group included that burnout i...
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PURPOSE: Oncology clinical research coordinators (CRCs) and team-based coordinator care are critical for the success of clinical trials. However, CRCs typically report elevated anxiety and burnout and many oncology centers have high... more
PURPOSE: Oncology clinical research coordinators (CRCs) and team-based coordinator care are critical for the success of clinical trials. However, CRCs typically report elevated anxiety and burnout and many oncology centers have high levels of coordinator attrition. To address the need for a team-based intervention to reduce burnout and promote resilience and cohesion among CRCs, we developed a compassion-centered, team-based intervention, Compassion-Centered Spiritual Health Team Intervention (CCSH-TI). METHODS: Participants were CRCs working in disease-specific teams within a comprehensive cancer center. CRCs were randomly assigned by team to either participate in four 60-minute sessions of CCSH-TI or receive the intervention after the study. To evaluate whether CCSH-TI is feasible and acceptable, we used a mixed-method approach including self-report questionnaires and a focus group. To evaluate the impact of CCSH-TI, we assessed self-reported resilience, well-being, burnout, and t...
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Accumulating evidence suggests that neuroinflammation is involved in bipolar disorder (BD) pathogenesis. The tumor necrosis factor-alpha (TNF-α) antagonist infliximab was recently reported to improve depressive symptoms in a subpopulation... more
Accumulating evidence suggests that neuroinflammation is involved in bipolar disorder (BD) pathogenesis. The tumor necrosis factor-alpha (TNF-α) antagonist infliximab was recently reported to improve depressive symptoms in a subpopulation of individuals with BD and history of childhood maltreatment. To explore the mechanistic mediators of infliximab’s effects, we investigated its engagement with biomarkers of cellular response to inflammation derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We hypothesized that infliximab, compared to placebo, would decrease TNF-α receptors (TNFRs) and nuclear factor-kappa B (NF-κB) pathway signaling biomarkers, and that history of childhood abuse would moderate infliximab’s effects. We immunocaptured NEVs from plasma samples collected at baseline and at weeks 2, 6, and 12 (endpoint) from 55 participants of this clinical trial and measured NEV biomarkers using immunoassays. A subset of participants (n = 27) also underw...
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Evidence suggests that affective disorders are associated with altered thermoregulation, and it has been hypothesized that therapeutic strategies targeting body-to-brain thermosensory systems may be effective for treating depression.... more
Evidence suggests that affective disorders are associated with altered thermoregulation, and it has been hypothesized that therapeutic strategies targeting body-to-brain thermosensory systems may be effective for treating depression. Consistent with this hypothesis, a recent randomized, double blind, placebo-controlled clinical trial has suggested that infrared whole-body hyperthermia has therapeutic potential for the treatment of depression. Preclinical models may help uncover the mechanism/s underlying the antidepressant-like effects of whole-body heating. We have previously shown that exposure to whole-body heating potentiates antidepressant-like behavioural responses following administration of a behaviourally subthreshold dose of the selective serotonin reuptake inhibitor citalopram, but the neurochemical and behavioural interactions between whole body heating and behaviourally effective doses of citalopram are not known. In these experiments, we examined the effects of whole-body heating, either with or without treatment of a suprathreshold dose of citalopram (20 mg/kg, s.c.), on body temperature, antidepressant-like behavioural responses in the forced swim test, and tissue concentrations of serotonin and its metabolite, 5-hydoxyindoleacetic acid (5-HIAA), in the prefrontal cortex of adolescent male Wistar rats. Although whole-body heating did not potentiate the behavioural effects of suprathreshold citalopram, citalopram was observed to increase body temperature and potentiate the effects of whole-body heating on body temperature. Whole-body heating, by itself, decreased serotonin concentrations in the infralimbic cortex, to a level similar to that observed following treatment with citalopram, suggesting that these treatments have convergent effects on a mesolimbocortical system innervating the medial prefrontal cortex, an effect that was correlated with effects of treatment on body temperature.
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Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or... more
Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were examined using enzyme-linked immunosorbent assays. One-night fasting had no effect on fear acquisition but enhanced fear extinction retention and prevented the return of fear, and this effect persisted for at least 6 months. This procedure was also effective for remote fear memory. Plasma ghrelin levels were elevated after fasting and had a negative relationship ...
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Mindfulness has seen an extraordinary rise as a scientific construct, yet surprisingly little is known about how it manifests behaviorally in daily life. The present study identifies assumptions regarding how mindfulness relates to... more
Mindfulness has seen an extraordinary rise as a scientific construct, yet surprisingly little is known about how it manifests behaviorally in daily life. The present study identifies assumptions regarding how mindfulness relates to behavior and contrasts them against actual behavioral manifestations of trait mindfulness in daily life. Study 1 (N = 427) shows that mindfulness is assumed to relate to emotional positivity, quality social interactions, prosocial orientation and attention to sensory perceptions. In Study 2, 185 participants completed a gold-standard, self-reported mindfulness measure (the FFMQ) and underwent naturalistic observation sampling to assess their daily behaviors. Trait mindfulness was robustly related to a heightened perceptual focus in conversations. However, it was not related to behavioral and speech markers of emotional positivity, quality social interactions, or prosocial orientation. These findings suggest that the subjective and self-reported experience...
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The present study aimed to replicate and extend findings by Mehl, Vazire, Holleran and Clark (2010) that individuals with higher well-being tend to spend less time alone and more time interacting with others (e.g., greater conversation... more
The present study aimed to replicate and extend findings by Mehl, Vazire, Holleran and Clark (2010) that individuals with higher well-being tend to spend less time alone and more time interacting with others (e.g., greater conversation quantity), and engage in less small talk and more substantive conversations (e.g., greater conversation quality). To test the robustness of these effects in a larger and more diverse sample, we used Bayesian integrative data analysis to pool data on subjective life satisfaction and observed daily conversations from three heterogeneous adult samples, in addition to the original sample (N = 486). We found moderate associations between life satisfaction and amount of alone time, conversation time, and substantive conversations, but no reliable association with small talk. Personality did not substantially moderate these associations. The failure to replicate the original small talk effect is theoretically and practically important as it has garnered cons...
Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in... more
Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social-environmental variables more closely than they do self-reported internal affective states such as stress, depression, or anxiety. This study examined the possibility that variations in patterns of natural language use might provide more sensitive indicators of the automatic threat-detection and -response systems that proximally regulate autonomic induction of the CTRA. In 22,627 audio samples of natural speech sampled from the daily interactions of 143 healthy adults, both total language output and patterns of function-word use covaried with CTRA gene expression. These language features predicted CTRA gene expression substantially better than did conventional self-report measures ...
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Prior studies suggest that the inflammatory biomarker c-reactive protein (CRP) holds promise for predicting antidepressant response in patients with major depressive disorder. The objective of this study was to evaluate whether CRP might... more
Prior studies suggest that the inflammatory biomarker c-reactive protein (CRP) holds promise for predicting antidepressant response in patients with major depressive disorder. The objective of this study was to evaluate whether CRP might similarly predict antidepressant responses to lurasidone in patients with bipolar I depression. Serum CRP concentration was measured prior to, and following, 6 weeks of treatment in 485 outpatients with bipolar I depression. Patients were randomized to receive monotherapy with lurasidone 20-60 mg/day (N = 161), lurasidone 80-120 mg/day (N = 162) or placebo (N = 162). CRP was assessed using the wide-range CRP assay (wr-CRP). The primary efficacy endpoint was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Mixed models and statistical interaction tests were applied to investigate the moderating effects of pre-treatment wr-CRP on clinical endpoints. CRP was evaluated as a log-transformed continuous variable an...
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Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains... more
Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity...
Circulating concentrations of interleukin (IL)-6, an inflammatory biomarker widely assessed in humans to study the inflammatory response to acute psychological stress, have for decades been quantified using enzyme-linked immunosorbent... more
Circulating concentrations of interleukin (IL)-6, an inflammatory biomarker widely assessed in humans to study the inflammatory response to acute psychological stress, have for decades been quantified using enzyme-linked immunosorbent assay (ELISA). However, biobehavioral researchers are increasingly using cytokine multiplex assays instead of ELISA to measure IL-6 and other cytokines. Despite this trend, multiplex assays have not been directly compared to ELISA for their ability to detect subtle stress-induced changes of IL-6. Here, we tested the prediction that a high-sensitivity multiplex assay (human Magnetic Luminex Performance Assay, R&D Systems, Minneapolis, MN) would detect changes in IL-6 as a result of acute stress challenge in a manner comparable to high-sensitivity ELISA. Blood was collected from 12 healthy adults immediately before and then 90 and 210 min after the start of the Trier Social Stress Test (TSST), an acute laboratory psychosocial stress challenge. In additio...
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Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory... more
Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CC...
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Open and randomized, double blind, placebo-controlled clinical trials have demonstrated clinical efficacy of infrared whole-body hyperthermia in treatment of major depressive disorder (MDD). Demonstration of antidepressant-like behavioral... more
Open and randomized, double blind, placebo-controlled clinical trials have demonstrated clinical efficacy of infrared whole-body hyperthermia in treatment of major depressive disorder (MDD). Demonstration of antidepressant-like behavioral effects of whole-body hyperthermia in preclinical rodent models would provide further support for the clinical use of infrared whole-body hyperthermia for the treatment of MDD, and would provide additional opportunities to explore underlying mechanisms. Adolescent male Wistar rats were habituated daily for 7days to an incubator (23°C, 15min), then exposed to an 85-min period of whole-body hyperthermia (37°C) or control conditions (23°C), with or without pretreatment with a subthreshold dose of the selective serotonin reuptake inhibitor, citalopram (5mg/kg, s.c., 23h, 5h, and 1h before behavioral testing in a 5-min forced swim test). Rectal temperature was monitored daily and immediately before and after the forced swim test to determine the relatio...
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This review provides a critical perspective on recent meta-analyses suggesting that several anti-inflammatory modalities, including nonsteroidal anti-inflammatory drugs (NSAIDs), omega-3 fatty acids, and cytokine antagonist, possess... more
This review provides a critical perspective on recent meta-analyses suggesting that several anti-inflammatory modalities, including nonsteroidal anti-inflammatory drugs (NSAIDs), omega-3 fatty acids, and cytokine antagonist, possess generalizable antidepressant properties. By examining confounds and limitations in the available literature it is suggested that current data suggest that only a sub-group of individuals with major depressive disorder (MDD) have evidence of increased inflammatory biomarkers and it is in these individuals that anti-inflammatory agents show promise for reducing depressive symptoms. The treatment implications of this cautionary perspective are discussed.
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Dysregulated immune responses to stress are a potential pathway linking close relationship processes to health, and couples' abilities to cope with stress together (dyadic coping) likely... more
Dysregulated immune responses to stress are a potential pathway linking close relationship processes to health, and couples' abilities to cope with stress together (dyadic coping) likely impact such immune responses. Most stress research has focused on immune reactivity, whereas knowledge of immune recovery remains limited. The present study examined how acute interpersonal stress affects immune reactivity and recovery, as well as whether dyadic coping moderates these effects. Healthy couples (N = 24) completed the Dyadic Coping Inventory and provided saliva samples 4 times each day for 5 days, including 2 days before a laboratory dyadic stressor (discussing an area of disagreement), the day of, and 2 days after. Four additional saliva samples were taken throughout the laboratory stressor. Saliva samples were assayed for interleukin (IL)-6. Multilevel models that adjusted for demographic and health variables indicated that partners low in dyadic coping showed immune reactivity to the stressor whereas partners high in dyadic coping did not. Dyadic coping did not moderate immune recovery, which had occurred by 5 hr poststressor across all participants. Results suggest that partners low in dyadic coping show increased reactivity of immune responses to interpersonal stress. Enhancing dyadic coping in couples may impact not only their mental health and relationship quality, but also their risk of stress-related immune disorders. (PsycINFO Database Record
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Increasing data suggest that for medical school students the stress of academic and psychologicaldemands can impair social emotions that are a core aspect of compassion and ultimately physiciancompetence. Few interventions have proven... more
Increasing data suggest that for medical school students the stress of academic and psychologicaldemands can impair social emotions that are a core aspect of compassion and ultimately physiciancompetence. Few interventions have proven successful for enhancing physician compassion inways that persist in the face of suffering and that enable sustained caretaker well-being. To addressthis issue, the current study was designed to (1) investigate the feasibility of cognitively-basedcompassion training (CBCT) for second-year medical students, and (2) test whether CBCT decreasesdepression, enhances compassion, and improves daily functioning in medical students. Comparedto the wait-list group, students randomized to CBCT reported increased compassion, and decreasedloneliness and depression. Changes in compassion were most robust in individuals reporting highlevels of depression at baseline, suggesting that CBCT may benefit those most in need by breakingthe link between personal suffering and a concomitant drop in compassion
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Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression... more
Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.Neuropsychopharmacology accepted article preview online, 15 September 2016. doi:10.1038/npp.2016.194.
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The hygiene or "Old Friends" hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory... more
The hygiene or "Old Friends" hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these Old Friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here, we review recent advances in our understanding of the potential for Old Friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially derived metabolites, bacterial an...
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Background: Interferon (IFN)-α treatment frequently induces depression, which can impair quality of life and reduce treatment adherence. Defining relevant risk factors for IFN-α-induced depression is essential for designing preventative... more
Background: Interferon (IFN)-α treatment frequently induces depression, which can impair quality of life and reduce treatment adherence. Defining relevant risk factors for IFN-α-induced depression is essential for designing preventative treatment strategies. Objective: The purpose of the present study was to determine whether promoter polymorphisms of –408C/T, –3C/T and GT repeat dinucleotide microsatellite in the IFN-α/β receptor 1 (IFNAR1) gene are
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Research Interests: Brain, Humans, Major Depressive Disorder, Animals, Microglia, and 11 moreMonoclonal Antibodies, Risk factors, Adult, Combination drug therapy, Risk Factors, Encephalitis, Life Change Events, Randomized Controlled Trials as Topic, Psychology and Cognitive Sciences, Medical and Health Sciences, and Antidepressive agents
Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may... more
Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Co...
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Poor marital quality is associated with many different indicators of poor health, including immunologic and metabolic responses that have relevance for distal disease outcomes such as diabetes. We conducted this study to evaluate whether... more
Poor marital quality is associated with many different indicators of poor health, including immunologic and metabolic responses that have relevance for distal disease outcomes such as diabetes. We conducted this study to evaluate whether poor marital quality was associated with the prevalence of diabetes in a population-based sample of Americans over the age of 50. Participants were married adults from the 2006 (N = 3,898) and 2008 (N = 3,452) waves of the Health and Retirement Study. Participants completed an interview and a self-report questionnaire, and current use of diabetes medication and glycosylated hemoglobin obtained from blood spot samples were used to index diabetes status. Marital quality was assessed with items regarding perceived frequency of positive and negative exchanges with partner. Decreasing frequency of positive exchanges and increasing frequency of negative exchanges with one's spouse were associated with higher prevalence of diabetes among men, but not women at both waves; gender significantly moderated the associations between partner exchanges and diabetes status for the 2006 data. The association between frequency of partner exchanges and diabetes status generally remained significant in men after accounting for demographic characteristics and other risk factors (obesity, hypertension, low physical activity). Poor marital quality as operationalized by rates of positive and negative partner exchanges was associated with increased prevalence of diabetes in men. These results are consistent with prior work on marriage and health, and suggest that poor marital quality may be a unique risk factor for diabetes.
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Lecturing around the country has left us with the powerful impression that both psychiatrists and primary care physicians are hungry for new ways to think about and manage depression and the myriad symptoms and syndromes with which it is... more
Lecturing around the country has left us with the powerful impression that both psychiatrists and primary care physicians are hungry for new ways to think about and manage depression and the myriad symptoms and syndromes with which it is associated—including attention deficit disorder, insomnia, chronic pain conditions, substance abuse, and various states of disabling anxiety.
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Research Interests: Face recognition (Psychology), Humans, Risk factors, Mood Disorders, Prevalence, and 11 moreNeoplasms, Risk Factors, CNS drugs, chronic hepatitis C, Neurosciences, Antiviral Agents, Interferon Alpha, Behavioral symptoms, Psychiatric Status Rating Scales, Adverse effect, and Pharmacology and pharmaceutical sciences
The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative... more
The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunizati...
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ABSTRACT Editor’s note: The World Health Organization predicts that depression, which already affects about 10 percent of the population in the United States, will be the world’s leading medical condition by 2030. Evidence suggests... more
ABSTRACT Editor’s note: The World Health Organization predicts that depression, which already affects about 10 percent of the population in the United States, will be the world’s leading medical condition by 2030. Evidence suggests several causes for depression, including traumatic life events, disease, poison, and nutritional deficiencies. Many of these causes are associated with elevated levels of inflammatory biomarkers in the blood, which may in turn lead to inflammatory changes in the brain. Our authors examine what the latest research reveals about link between inflammation in the brain and depression, and how a better understanding of that link can play a critical first step in the personalization of care.
Research Interests: Immune response, Depression, Cytokines, Hepatitis C, Biological Sciences, and 15 moreMolecular, Cerebrospinal Fluid, Humans, Female, Male, Behavior change, Central Nervous System, Middle Aged, Longitudinal Studies, Adult, Depressive Symptoms, Enzyme Linked Immunosorbent Assay, Antiviral Agents, Interferon Alpha, and Medical and Health Sciences
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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... more
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 previously reported that patients with hepatitis C virus chronically administered interferon (IFN)-alpha develop increased evening plasma cortisol concentrations and a flattened diurnal cortisol slope, which correlated with increased tumor necrosis factor (TNF) and its soluble receptor 2 (sTNFR2). Increased TNF and sTNFR2 were further correlated with depression and fatigue scores. The current study examined whether flattened cortisol slope might be secondary to reduced glucocorticoid receptor (GR) sensitivity, by measuring glucocorticoid negative feedback to dexamethasone (DEX) administration followed by corticotropin releasing hormone (CRH) challe...
Research Interests: Depression, Inflammation, Fatigue, Hepatitis C, Corticotropin Releasing Hormone, and 15 moreBiological Sciences, Dexamethasone, Humans, Female, Male, Middle Aged, Longitudinal Studies, Adult, Adrenocorticotropic Hormone, Glucocorticoids, Area Under Curve, Antiviral Agents, Interferon Alpha, hydrocortisone, and Medical and Health Sciences
Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with... more
Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.