Social and Behavioral Sciences Commons^™

Proteomic Profiles Of Cytokines And Chemokines In Moderate To Severe Depression: Implications For Comorbidities And Biomarker Discovery, Kathleen T. Watson, Jennifer Keller, Caleb M. Spiro, Isaac B. Satz, Samantha V. Goncalves, Heather Pankow, Idit Kosti, Benoit Lehallier, Adolfo Sequeira, William E. Bunney, Natalie L. Rasgon, Alan F. Schatzberg

Psychology Division Scholarship

Objective: This study assessed the proteomic profiles of cytokines and chemokines in individuals with moderate to severe depression, with or without comorbid medical disorders, compared to healthy controls. Two proteomic multiplex platforms were employed for this purpose. Metods: An immunofluorescent multiplex platform and an aptamer-based method were used to evaluate 32 protein analytes from 153 individuals with moderate to severe major depressive disorder (MDD) and healthy controls (HCs). The study focused on determining the level of agreement between the two platforms and evaluating the ability of individual analytes and principal components (PCs) to differentiate between the MDD and HC groups. …

Biological Correlates Of The Effects Of Auricular Point Acupressure On Pain, Chao Hsing Yeh, Nada Lukkahatai, Xinran Huang, Hulin Wu, Hongyu Wang, Jingyu Zhang, Xinyi Sun, Thomas J Smith

Journal Articles

BACKGROUND: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers.

DESIGN: This is a secondary data analysis.

METHODS: Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for …

Individual Differences In The Coordinated Behavioral And Physiological Immune Response To Pathogenic Threat, Edwin Joel Rosales-Vijil

Cal Poly Humboldt theses and projects

Previous research has shown that simply viewing a pathogenic threat (e.g., a photo of someone sneezing) can trigger our immune systems to activate. Activation of the immune system can be measured through a variety of physiological markers, including inflammatory cells (i.e., cytokines) in the blood or saliva. The current study aims to replicate that finding that viewing pathogen-relevant images will trigger an immune response, and extend this work by investigating whether individual differences in perceived vulnerability to disease impacts the size of this immune response.

Utilization Of The Fundamental Attribution Error With Increased Immune System Inflammation, John Odom

Biological Sciences Undergraduate Honors Theses

Immune system inflammation is associated with sickness behavior, depressive mood, and alteration of decision-making processes. Because of these cognitive effects, inflammation may also lead to increased use of heuristics, for example the Fundamental Attribution Error (FAE). In the current research, inflammation was experimentally increased using the influenza vaccine, with participants receiving either the vaccine or a placebo injection and completing a measure that tests for the FAE. There were no significant differences between the two conditions regarding the number of personal, situational, or overall attributions made by the participants in the measure that would indicate use of the FAE. However, …

Baseline And Stress-Induced Cognitive Control Deficits And Pro-Inflammatory Cytokines In Currently, Remitted, And Never Depressed Individuals, Katerina Rnic

Electronic Thesis and Dissertation Repository

Background: Cognitive theories posit that cognitive control deficits promote depression by reducing ability to self-regulate under stress. When activated by stress and accessible to working memory, negative cognitive content and structure (i.e., schemas), may interfere with cognitive control abilities, resulting in even greater declines in executive functioning. Moreover, burgeoning evidence indicates that social stress upregulates inflammation, resulting in a pro-inflammatory phenotype that drives depression pathogenesis. However, cognitive mechanisms underlying this process are not well understood. An objective of this study was to examine depression-related deficits in cognitive control and their association with poor self-regulation. Another purpose was to evaluate the …

Associations Of First Trimester Co-Use Of Tobacco And Cannabis With Prenatal Immune Response And Psychosocial Well-Being, Kristin Ashford, Amanda Fallin-Bennett, Andrea Mccubbin, Amanda T. Wiggins, Sheila Barnhart, Joshua A. Lile

Perinatal Research and Wellness Center Faculty Publications

PURPOSE: This study aims to describe the association of first trimester co-use of tobacco and cannabis with maternal immune response and psychosocial well-being, relative to tobacco use only.

METHODS: A preliminary midpoint analysis included 138 pregnant women with biologically verified tobacco use, 38 of whom (28%) also tested positive for recent cannabis use. Maternal perceived stress (Perceived Stress Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and serum immune markers (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, CRP, MMP8), were collected, although cytokine data were only available for 122 women.

RESULTS: Participant average age was 29.1 years, approximately half had a high …

Neuroimmune-Mediated Alcohol Effects On Ventral Tegmental Area Microglia And Infiltrating Leukocytes, Travis Jonathan Clarke

Theses and Dissertations

Microglia are the primary immune cell in the central nervous system and are known as the “resident” macrophages in the central nervous system (CNS). While microglia are classically known as the immune cells of the CNS, their role has more recently been shown to extend far beyond immunity. The effects of ethanol on the brain are closely linked to neuroimmune responses mediated by microglia that are present in the healthy brain from the time of development. Though microglia have been classified as the “resident” immune cells of the CNS, new research suggests that other immune cells may be implicated in …

Association Between The Magnitude Of The Immune Response And Recurrent Major Depression Disorder In Humans And Depression-Like Behavior In Animals, Anastacia Kudinova

Graduate Dissertations and Theses

There is a growing body of evidence supporting the association between inflammation and major depressive disorder (MDD). One plausible mechanism for this association is sensitization of the immune response, possibly due to prior exposure to stressors. To investigate the validity of this hypothesis, a series of three complimentary cross-species studies was conducted. Study 1 examined the associations between circulating levels of inflammatory markers and in vitro immune reactivity with women’s history of recurrent MDD (rMDD) and their current symptoms of anhedonia. The potential moderating role of women’s history of childhood abuse was also examined. Study 2 and 3 focused on …

Cumulative Trauma, Emotion Reactivity And Salivary Cytokine Response Following Acute Stress Among Healthy Women., Yvette Z. Szabo

Electronic Theses and Dissertations

This study furthers understanding of how trauma exposure may be connected to the development and maintenance of poor health by focusing on cytokines, tightly regulated proteins of the immune system. Cytokine responses to acute stress have been associated with the onset of poorer mental health in physically healthy women. The present study examined how two factors recently associated with cytokine reactivity –cumulative trauma and emotion reactivity– are associated with salivary cytokine reactivity among healthy women. Seventy-one women, screened to be physically and mentally healthy, completed a laboratory acute stress paradigm and self-report measures of state emotion and trauma exposure. Participants …

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

Time-Dependent Effects Of Cx3cr1 In A Mouse Model Of Mild Traumatic Brain Injury, Heidi Y. Febinger, Hannah E. Thomasy, Maria N. Pavlova, Kristyn M. Ringgold, Paulien R. Barf, Amrita M. George, Jenna N. Grillo, Adam D. Bachstetter, Jenny A. Garcia, Astrid E. Cardona, Mark R. Opp, Carmelina Gemma

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases.

METHODS: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

The P38alpha Mitogen-Activated Protein Kinase Limits The Cns Proinflammatory Cytokine Response To Systemic Lipopolysaccharide, Potentially Through An Il-10 Dependent Mechanism, Adam D. Bachstetter, Bin Xing, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α mitogen-activated protein kinase (MAPK) is a well-characterized intracellular kinase involved in the overproduction of proinflammatory cytokines from glia. As such, p38α appears to be a promising therapeutic target for neurodegenerative diseases associated with neuroinflammation. However, the in vivo role of p38α in cytokine production in the CNS is poorly defined, and prior work suggests that p38α may be affecting a yet to be identified negative feedback mechanism that limits the acute, injury-induced proinflammatory cytokine surge in the CNS.

METHODS: To attempt to define this negative feedback mechanism, we used two in vitro and two in vivo models …

Association Of Trauma Exposure With Proinflammatory Activity: A Transdiagnostic Meta-Analysis., M Tursich, R W J Neufeld, P A Frewen, S Harricharan, J L Kibler, S G Rhind, R A Lanius

Faculty Articles

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …