Browsing by Subject "Anxiety"
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Item Open Access A Peptide Selectively Uncoupling BDNF Receptor TrkB from Phospholipase C gamma 1 Prevents Epilepsy and Anxiety-like Disorder(2015) Gu, BinTemporal lobe epilepsy is a common and devastating disorder that features recurrent seizures and is often associated with pathologic anxiety and hippocampal sclerosis. An episode of prolonged seizures (status epilepticus) is thought to promote development of human temporal lobe epilepsy years later. A chemical-genetic approach established proof of concept that transiently inhibiting the receptor tyrosine kinase, TrkB, following status epilepticus prevented epilepsy, anxiety-like behavior and hippocampal damage in a mouse model, providing rationale for developing a therapeutic targeting TrkB signaling. To circumvent the undesirable consequence that global inhibition of TrkB exacerbates neuronal degeneration following status epilepticus, we sought to identify both the TrkB-activated signaling pathway mediating these pathologies and a compound that uncouples TrkB from the responsible signaling effector. To accomplish these goals, we used genetically modified mice and a model of seizures and epilepsy induced by a chemoconvulsant. Genetic inhibition of TrkB-mediated phospholipase C gamma 1 (PLC gamma 1) signaling suppressed seizures induced by a chemoconvulsant, leading to design of a peptide (pY816) that inhibited the interaction of TrkB with PLC gamma 1. We demonstrate that pY816 selectively inhibits TrkB-mediated activation of PLC gamma 1 both in vitro and in vivo. Treatment with pY816 prior to administration of a chemoconvulsant suppressed seizures in a dose- and time-dependent manner. Treatment with pY816 initiated after chemoconvulsant-evoked status epilepticus and continued for just three days suppressed seizure-induction of epilepsy, anxiety-like behavior and hippocampal damage assessed months later. This study elucidates the signaling pathway by which TrkB activation produces diverse neuronal activity-driven pathologies and demonstrates therapeutic benefits of an inhibitor of this pathway in an animal model in vivo. A strategy of uncoupling a receptor tyrosine kinase from a signaling effector may prove useful in diverse diseases in which excessive receptor tyrosine kinase signaling contributes.
Item Open Access Amygdala-prefrontal cortex functional connectivity during threat-induced anxiety and goal distraction.(Biol Psychiatry, 2015-02-15) Gold, Andrea L; Morey, Rajendra A; McCarthy, GregoryBACKGROUND: Anxiety produced by environmental threats can impair goal-directed processing and is associated with a range of psychiatric disorders, particularly when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought to implement controls that minimize performance disruptions from threat-induced anxiety and goal distraction by modulating activity in regions involved in threat detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of anxiety during threat exposure. We developed a paradigm to determine if threat-induced anxiety would enhance functional connectivity between the amygdala and IFG, OFC, and vmPFC. METHODS: Healthy adults performed a computer-gaming style task involving capturing prey and evading predators to optimize monetary rewards while exposed to the threat of unpredictable shock. Psychophysiological recording (n = 26) and functional magnetic resonance imaging scanning (n = 17) were collected during the task in separate cohorts. Task-specific changes in functional connectivity with the amygdala were examined using psychophysiological interaction analysis. RESULTS: Threat exposure resulted in greater arousal measured by increased skin conductance but did not influence performance (i.e., monetary losses or rewards). Greater functional connectivity between the right amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and frontopolar cortex was associated with threat exposure. CONCLUSIONS: Exposure to unpredictable threat modulates amygdala-PFC functional connectivity that may help maintain performance when experiencing anxiety induced by threat. Our paradigm is well-suited to explore the neural underpinnings of the anxiety response to unpredictable threat in patients with various anxiety disorders.Item Open Access Assessment of the psychometric properties of an English version of the cancer dyspnea scale in people with advanced lung cancer.(Journal of pain and symptom management, 2012-11) Uronis, Hope E; Shelby, Rebecca A; Currow, David C; Ahmedzai, Sam H; Bosworth, Hayden B; Coan, April; Abernethy, Amy PContext
Dyspnea is a poorly understood subjective sensation. Existing dyspnea measures fail to adequately address its multidimensionality. A Japanese group developed and validated the Cancer Dyspnea Scale (CDS) for assessing dyspnea in patients with advanced lung cancer.Objectives
We evaluated the validity and reliability of the English version of the CDS (CDS-E) that has 12 items and takes, on average, 140 seconds for individuals to complete.Methods
Eligible patients had advanced lung cancer, consented, and were fluent in English. Participants completed a 100 mm visual analogue scale (VAS), the modified Borg scale, the CDS-E, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy--Lung quality-of-life scale. Demographic, radiographic, and treatment information were obtained from patients' medical records.Results
One hundred twelve participants were enrolled at three sites in the U.S., Australia, and the U.K. Mean age was 64.5 years (SD 11.5); 90% were Caucasian, 68% had Eastern Cooperative Oncology Group performance status 0-1, and 50% had non-small cell carcinoma. All completed the CDS-E independently, without difficulty. The CDS-E had reasonable internal consistency overall (Cronbach's α = 0.71) and for each of the three factors (effort, anxiety, discomfort Cronbach's α = 0.80-0.84). CDS-E scores were significantly correlated with the 100mm VAS (r = 0.82; P < 0.001) and the modified Borg (r = 0.87; P < 0.001). After factor analysis, the CDS-E was revised by removing three items (r-CDS-E).Conclusion
The CDS-E and r-CDS-E are reliable and valid measures of the sensation and the psychological components of dyspnea, with the shorter version having similar psychometric properties.Item Open Access Association of anxiety and depression with all-cause mortality in individuals with coronary heart disease.(J Am Heart Assoc, 2013-03-19) Watkins, Lana L; Koch, Gary G; Sherwood, Andrew; Blumenthal, James A; Davidson, Jonathan RT; O'Connor, Christopher; Sketch, Michael HBACKGROUND: Depression has been related to mortality in coronary heart disease (CHD) patients, but few studies have evaluated the role of anxiety or the role of the co-occurrence of depression and anxiety. We examined whether anxiety is associated with increased risk of mortality after accounting for depression in individuals with established CHD. METHODS AND RESULTS: The cohort was composed of 934 men and women with confirmed CHD (mean age, 62±11 years) who completed the Hospital Anxiety and Depression scale (HADS) during hospitalization for coronary angiography. Over the 3-year follow-up period, there were 133 deaths. Elevated scores on the HADS anxiety subscale (HADS-A≥8) were associated with increased risk of mortality after accounting for established risk factors including age, congestive heart failure, left ventricular ejection fraction, 3-vessel disease, and renal disease (hazard ratio [HR], 2.27; 95% CI, 1.55 to 3.33; P<0.001). Elevated scores on the HADS depression subscale (HADS-D≥8) were also associated with increased risk of mortality (HR, 2.18; 95% CI, 1.47 to 3.22; P<0.001). When both psychosocial factors were included in the model, each maintained an association with mortality (anxiety, HR, 1.83; 95% CI, 1.18 to 2.83; P=0.006; depression, HR, 1.66; 95% CI, 1.06 to 2.58; P=0.025). Estimation of the HR for patients with both anxiety and depression versus those with neither revealed a larger HR than for patients with either factor alone (HR, 3.10; 95% CI, 1.95 to 4.94; P<0.001). CONCLUSIONS: Anxiety is associated with increased risk of mortality in CHD patients, particularly when comorbid with depression. Future studies should focus on the co-occurrence of these psychosocial factors as markers of increased mortality risk.Item Open Access Association of self-directed walking with toxicity moderation during chemotherapy for the treatment of early breast cancer.(Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2023-12) Nyrop, KA; Page, A; Deal, AM; Wagoner, C; Kelly, EA; Kimmick, Gretchen G; Copeland, Anureet; Speca, JoEllen; Wood, William A; Muss, HBBackground
In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy.Methods
Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model.Results
In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03).Conclusion
Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer.Trial numbers
NCT02167932, NCT02328313, NCT03761706.Item Open Access Can’t You Feel Your Heartbeat Fast?: Mindfulness as a mediator between interoception and anxiety(2019-04) Yang, IrisInteroception is the perception of physical and emotional sensations within the body, such as hunger, respiration, and pain. Interoception is conceptualized in different components, including interoceptive accuracy (IAc), operationalized in this study as the objective ability to detect heartbeats within the body, and interoceptive sensibility (IS), measured by self-reports of subjective interoception. There is conflicting literature on whether or not interoception is helpful or hurtful in emotion regulation. In an undergraduate, nonclinical sample, we hypothesized that: (1) IAc will not significantly correlate with IS; (2) mindfulness will mediate the effect of IS on anxiety such that IS will predict higher anxiety at low levels of mindfulness while IS will predict low anxiety at high levels of mindfulness; (3) mindfulness will mediate the effect of IAc on anxiety such that better IAc will predict higher anxiety at low levels of mindfulness while better IAc will predict low anxiety at high levels of mindfulness. As hypothesized, accuracy on the heartbeat perception task (IAc) was not significantly correlated with IS (p =.52). In contrast to hypotheses 2 and 3, multiple linear regression models did not show interoception mediating the relationship between mindfulness and anxiety. Further studies should be conducted in clinical populations to investigate the relationships between interoception, mindfulness, and anxiety.Item Open Access Cognitive Processes in Response to Goal Failure: A Study of Ruminative Thought and its Affective Consequences.(J Soc Clin Psychol, 2013-05-01) Jones, NP; Papadakis, AA; Orr, CA; Strauman, TJFailure to make progress toward personal goals can lead to negative affective states, such as depression and anxiety. Past research suggests that rumination in response to goal failure may prolong and intensify those acute emotional responses, but that process remains unclear. We examined ruminative thought processes following experimentally manipulated exposure to past failures to attain advancement (promotion) goals and safety (prevention) goals. We predicted that priming of past promotion and prevention goal failures would lead individuals to think repetitively about these failures and that negative affect would be evoked by their recognition of their failures. Further, we predicted that when people experience a sufficient magnitude of negative affect, ruminative thought would intensify and prolong the negative affect associated with that type of goal failure. Results yielded strong support for our predictions regarding promotion goal failure and modest support for those regarding prevention goal failure.Item Open Access Comfort Zone Orientation: Moving Beyond One’s Comfort Zone(2018-04-25) Kiknadze, NonaAlthough people often talk about behaviors or experiences being “out of their comfort zone,” no research has examined the relationship between people’s comfort zones and how they react to situations that fall outside them. Three studies examined comfort zones and the value that some people place on pushing themselves out of their comfort zones, termed comfort zone orientation (CZO). Study 1 showed that people are able to answer questions about their comfort zones and that comfort zones are related to the emotions that people expect to experience in threatening situations. Study 2 validated a measure of CZO, showing that correlations between CZO and personality measures were consistent with its conceptualization. Study 3 was a laboratory experiment that revealed that CZO related to participants’ responses to an actual anxiety-producing task and that participants who valued pushing themselves out of their comfort zone were more confident that they could make themselves perform a threatening task. This research extends our understanding of the psychological basis of comfort zones and demonstrates that the Comfort Zone Orientation Scale is a valid measure of the degree to which people value pushing themselves out of their comfort zone.Item Open Access Creative Impulse in the Modern Age: The Embodiment of Anxiety in the Early Poetry of T. S. Eliot (1910-1917)(2017-05-04) Mukamal, AnnaThrough focused analysis of T. S. Eliot’s early poetry (1910-1917), this work investigates whether, and if so, how anxiety may be worthwhile or particularly constructive for poetic production in the modern world. In order to explore the connection between anxiety and artistic production, I analyze the presence of skepticism, inaction, solipsism, and despair in Eliot’s self-lacerating and morbidly self-conscious personae. I also discuss the rhetorical means by which he conveys disembodied agency, stunted volition, and seemingly unattainable self-possession. Eliot's evocation of repetitive thought processes—mirroring self-paralysis as actions are dissociated from agents—coincides with his search for an overarching morality to transcend the banal propriety of his sociocultural milieu. Manifesting his preoccupation with social and spiritual decadence, the embodied anxiety in Eliot’s verse reveals his profound desire to confront it, both in himself and in his deeply troubled, war-embittered age.Item Open Access Emotional Responses and Mother-Infant Interactions of Mothers with Early-Preterm, Late-Preterm, and Full-Term Infants in Malawi(2018) Gondwe, Kaboni WhitneyMalawi has the highest preterm birth rate in the world and preterm birth contribute to more than one-third of the neonatal deaths annually. Malawi is also faced with limited resources, both human and material. The lack of incubators led to the adoption of Kangaroo Mother Care (KMC) as routine care for preterm infants. Families also provide support, physical and emotional during this entire period. Evidence from developed countries has shown that preterm birth contributes to maternal emotional distress (depressive, anxiety, and posttraumatic stress symptoms and maternal worry about child’s health) and fewer maternal and infant interactive behaviors. The majority of published research globally has also focused on early-preterm infants and little research has been done on late-preterm infants. Studies in Malawi have also largely focused on postpartum depression and no published literature could be located on mother-infant-interactions. The purpose of this study was to explore emotional distress and mother-infant interactions of mothers with early-preterm, late-preterm, and full-term infants in Malawi.
This mixed method study and three-part investigation was conducted at Queen Elizabeth Central Hospital. The first part of the investigation was translation and validation of the Perinatal PTSD Questionnaire and the Child Health Worry Scale as measures for posttraumatic stress symptoms and maternal worry about child’s health, respectively. I conducted a focus group discussion with Malawian nurse-midwives (N=8) to assess content of translations in relation to original. I also tested the instruments on mothers in the perinatal period (N=30; 10 mothers of early-preterm infants, 10 mothers of late-preterm infants, and 10 mothers of full-term infants). Validated instruments from first phase were used in the second phase of the study. The second phase of the investigation compared emotional distress and mother infant interactions among 85 mother-infant dyads (28 mothers with their early-preterm, 29 mothers with their late-preterm, and 28 mothers with their full-term infants). Baseline assessments were done following birth for the three groups and follow-up assessments were conducted for mothers of the preterm groups. I also recorded and coded videos of mothers and infants to assess mother-infant interactions. The third phase of the investigation was qualitative (N= 19; 7 mothers with early-preterm infants, 7 mothers with late-preterm infants, and 5 mothers of full-term infants) and explored maternal perceptions of sources of concerns and social support following birth of their infants. In-depth interviews were conducted at the end of the study.
Findings showed that mothers of early-preterm infants experienced higher levels of emotional distress than mothers of full-term infants, with mothers of late-preterm infants being intermediate between the two. Cesarean birth was also associated with more anxiety and depressive symptoms. Kangaroo Mother Care had minimal effects on the change of emotional distress in mothers of the preterm groups. However, KMC interruptions were associated with an increase in emotional distress. Minimal differences were seen in mother-infant interactions among the mothers and infants of the three groups. KMC had no impact on the interactive behaviors. Mothers’ concerns during infant hospitalization were personal and family factors; prenatal and perinatal experiences; infant illness, treatments, and appearance; concerns about the infant’s outcome; loss of parental role; health care workers and the healthcare system; infant care including breastfeeding concerns; and provision of KMC. Types of support received during the hospitalization included instrumental/tangible support, emotional support including spiritual support, and financial support. Mothers also preferred to have their own family as their caregivers during hospitalization.
Future studies need to focus on longitudinal methods to explore whether emotional distress experiences change over time and also to explore maternal and infant interactive behaviors as the babies mature. The Malawi healthcare system needs to provide support for mothers throughout the prenatal and perinatal period in order to lower maternal distress symptoms and promote positive mother-infant interactions.
Item Open Access Evaluating risk for adolescent anxiety: The role of preschool sensory over-responsivity and differential volume of subcortical regions(2023-04-20) Haughey, ConnorAnxiety disorders represent one of the most prevalent groups of mental health disorders and can cause immense problems in psychosocial functioning and overall well-being. Sensory over-responsivity, which is typically only evaluated as a symptom of autism spectrum disorder, represents when an individual experiences an abnormally heightened reaction to at least one sensory stimulus. Recent studies have found that sensory over-responsivity at preschool age is associated with many forms of psychopathology at school age, including anxiety disorders. At present, no studies have examined if this relationship continues later in life nor how sensory over-responsivity manifests structurally in the brain. The primary aim of the present study was to evaluate whether preschool sensory over-responsivity is associated with adolescent anxiety, and whether the volumes of the amygdala, hippocampus, and caudate nucleus at school age might moderate this relationship. We conducted a longitudinal follow-up study that has a sample of 210 adolescents ages 15 to 22 who underwent psychiatric assessment at the preschool age, which included a diagnostic screening for anxiety disorders and sensory over-responsivity. A subset of these 210 adolescents also underwent magnetic resonance brain imaging at school age. At the most recent follow-up, they completed an assessment of anxiety, allowing us to investigate mental health changes across their lifespan. First, we found no significant relationship between preschool sensory over-responsivity and adolescent anxiety. Second, we did not find any significant moderation effect of bilateral amygdala, hippocampus, and caudate nucleus volumes on the relationship between preschool sensory over-responsivity and adolescent anxiety. However, we found a significant interaction between left hippocampus volume at school-age and preschool sensory over-responsivity on total externalizing and internalizing problems. These findings add to the growing literature seeking to understand early life risk factors for anxiety during adolescence. Furthermore, these findings emphasize the role of brain structure, particularly the hippocampus, during early life development in a model of risk for adolescent anxiety.Item Open Access Food for Thought: How Skipping Lunch and Psychiatric Illness Affect Cognition(2019-04-18) Bidopia, TatyanaMeal skipping is a common disordered eating behavior in college-aged individuals. This behavior is associated with a variety of health risks, including nutritional deficits and an increased risk for eating pathology. Research has indicated that meal skipping is also associated with impairments in various domains of cognitive functioning, including in tasks involving working memory, sustained attention, and set-shifting ability. However, a "post-lunch dip" in cognitive performance has been shown in individuals who consume lunch for approximately two hours after consumption. Possible moderating factors within the relationship between meal skipping and cognitive functioning have yet to be examined, particularly in regards to the presence of psychopathology. Both depression and anxiety symptoms have been associated with impairments in tasks involving working memory, sustained attention, set-shifting ability, and motor speed, indicating that individuals with these disorders may be particularly vulnerable to cognitive impairments seen with meal skipping behavior. This study investigated how skipping lunch affects various domains of cognitive functioning (working memory, sustained attention, set-shifting ability, and motor speed) after the post-lunch dip period in a sample of college students (aged 18-25; N = 99), primarily focusing on whether depression and/or anxiety symptoms moderate this relationship. Understanding the mechanisms by which meal skipping behavior affects cognition by examining potential moderating effects of common eating disorder comorbidities, such as depression and anxiety, has implications for encouraging healthier eating habits and preventing eating disorder onset in a vulnerable population.Item Open Access Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies.(J Clin Psychiatry, 2011-06) Davidson, Jonathan RT; Crawford, Cindy; Ives, John A; Jonas, Wayne BOBJECTIVE: To systematically review placebo-controlled randomized trials of homeopathy for psychiatric conditions. DATA SOURCES: Eligible studies were identified using the following databases from database inception to April 2010: PubMed, CINAHL, PsycINFO, Hom-Inform, Cochrane CENTRAL, National Center for Complementary and Alternative Medicine grantee publications database, and ClinicalTrials.gov. Gray literature was also searched using Google, Google Scholar, the European Committee for Homeopathy, inquiries with homeopathic experts and manufacturers, and the bibliographic lists of included published studies and reviews. Search terms were as follows: (homeopath* or homoeopath*) and (placebo or sham) and (anxiety or panic or phobia or post-traumatic stress or PTSD or obsessive-compulsive disorder or fear or depress* or dysthym* or attention deficit hyperactivity or premenstrual syndrome or premenstrual disorder or premenstrual dysphoric disorder or traumatic brain injury or fibromyalgia or chronic fatigue syndrome or myalgic encephalitis or insomnia or sleep disturbance). Searches included only English-language literature that reported randomized controlled trials in humans. STUDY SELECTION: Trials were included if they met 7 criteria and were assessed for possible bias using the Scottish Intercollegiate Guidelines Network (SIGN) 50 guidelines. Overall assessments were made using the Grading of Recommendations Assessment, Development and Evaluation procedure. Identified studies were grouped into anxiety or stress, sleep or circadian rhythm complaints, premenstrual problems, attention-deficit/hyperactivity disorder, mild traumatic brain injury, and functional somatic syndromes. RESULTS: Twenty-five eligible studies were identified from an initial pool of 1,431. Study quality according to SIGN 50 criteria varied, with 6 assessed as good, 9 as fair, and 10 as poor. Outcome was unrelated to SIGN quality. Effect size could be calculated in 16 studies, and number needed to treat, in 10 studies. Efficacy was found for the functional somatic syndromes group (fibromyalgia and chronic fatigue syndrome), but not for anxiety or stress. For other disorders, homeopathy produced mixed effects. No placebo-controlled studies of depression were identified. Meaningful safety data were lacking in the reports, but the superficial findings suggested good tolerability of homeopathy. A funnel plot in 13 studies did not support publication bias (χ(2)(1) = 1.923, P = .166). CONCLUSIONS: The database on studies of homeopathy and placebo in psychiatry is very limited, but results do not preclude the possibility of some benefit.Item Open Access Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey.(Curr Med Res Opin, 2014-01) Gan, Tong J; Habib, Ashraf S; Miller, Timothy E; White, William; Apfelbaum, Jeffrey LOBJECTIVE: During the past two decades, professional associations, accrediting bodies, and payors have made post-surgical pain treatment a high priority. In light of the disappointing findings in previous surveys, a survey was conducted to assess patient perceptions and characterize patient experiences/levels of satisfaction with post-surgical pain management. RESEARCH DESIGN AND METHODS: Survey included a random sample of US adults who had undergone surgery within 5 years from the survey date. Participants were asked about their concerns before surgery, severity of perioperative pain, pain treatments, perceptions about post-surgical pain and pain medications, and satisfaction with treatments they received. RESULTS: Of the 300 participants, ∼86% experienced pain after surgery; of these, 75% had moderate/extreme pain during the immediate post-surgical period, with 74% still experiencing these levels of pain after discharge. Post-surgical pain was the most prominent pre-surgical patient concern, and nearly half reported they had high/very high anxiety levels about pain before surgery. Approximately 88% received analgesic medications to manage pain; of these, 80% experienced adverse effects and 39% reported moderate/severe pain even after receiving their first dose. STUDY LIMITATIONS: Key study limitations include the relatively small population size, potential for recall bias associated with the 14-month average time delay from surgery date to survey date, and the inability to account for influences of type of surgery and intraoperative anesthetic/analgesic use on survey results. CONCLUSIONS: Despite heightened awareness and clinical advancements in pain management, there has been little improvement in post-surgical analgesia as measured by this survey of post-surgical patients.Item Open Access Interoceptive Contributions to Motivational and Affective Modulators of Memory Formation(2015) Rainey, CourtneaBiological drives such as hunger, thirst, and sexual reproduction are potent motivators of behavior. Extrinsic rewards in the environment (i.e. food, drink, money) are also important behavioral and cognitive motivators. In addition to the relevance of an extrinsic reward in meeting the needs of biological drives, an individual’s sensitivity to the physiological state of their body (interoceptive awareness) would also be expected to mediate motivation for these extrinsic primary rewards (i.e. food, drink). Importantly, a better characterization of the predicted behavioral and neural interactions between interoception, motivation, and memory systems can highlight novel targets for interventions to facilitate motivation and memory for adaptive behaviors and/or impede motivation and memory for maladaptive behaviors (i.e. addiction, relapse, overeating).
The present dissertation examines how individual differences in interoceptive awareness may modulate motivated memory formation via motivational and affective mechanisms. Specifically, interoceptive accuracy is associated with increased motivation for relevant primary rewards and enhanced encoding for these rewards. However, anxiety, negatively predicted by interoceptive accuracy, negatively predicts memory the next day. Furthermore, memory for relevant primary rewards was negatively predicted by insula-parahippocampal and ventral tegmental area-hippocampal background connectivity.
Item Open Access Is Everything Really Okay?: Anxious Reassurance Seeking as a Predictor of Stress Generation(2020) Meyer, Allison ElizabethNEED TO GO BACK AND ENTER WHEN I AM SURE IT IS COMPLETE
Item Open Access Medication non-adherence after myocardial infarction: an exploration of modifying factors.(Journal of general internal medicine, 2015-01) Crowley, Matthew J; Zullig, Leah L; Shah, Bimal R; Shaw, Ryan J; Lindquist, Jennifer H; Peterson, Eric D; Bosworth, Hayden BBackground
Medication non-adherence is a major impediment to the management of cardiovascular disease risk factors. A better understanding of the modifying factors underlying medication non-adherence among individuals with known cardiovascular disease may inform approaches for addressing non-adherence.Objective
The purpose of this study was to identify demographic and patient characteristics, medical comorbidities, psychosocial factors, and health belief-related factors associated with medication non-adherence among patients with known cardiovascular disease.Design
We performed secondary analysis of baseline data from a randomized trial.Patients
The study included 405 patients with a diagnosis of hypertension and history of acute myocardial infarction that was diagnosed within a three-year period prior to enrollment.Main measures
Baseline demographics and patient characteristics, medical comorbidities, psychosocial factors, health belief-related factors, and patient-reported medication non-adherence were analyzed.Key results
Of 405 patients, 173 (42.7 %) reported medication non-adherence. Factors associated with non-adherence in bivariate analysis included younger age, non-white race, having less than 12 years of education, smoking, financial insecurity, identifying as nervous or tense, higher life chaos score, greater worry about having a myocardial infarction, and greater worry about having a stroke. Using multivariable modeling, we determined that age (OR 0.97 per additional year, 95 % CI, 0.95-0.99), life chaos (OR 1.06 per additional point, 95 % CI, 1.00-1.11), and worry about stroke (OR 1.12 per additional point, 95 % CI, 1.01-1.25) remained significantly associated with self-reported medication non-adherence.Conclusions
We found that worry about having a stroke, higher life chaos, and younger age were all significantly associated with self-reported medication non-adherence in patients with cardiovascular disease and a history of myocardial infarction. Further research exploring these factors as targets for intervention is needed, as is additional research examining modifiable causes of medication non-adherence among patients with cardiovascular disease.Item Open Access Mental Health of the Latinx Community in the United States(2023-04-20) Junek, AmandaRecent spark in political activism for minority communities in combination with social de-stigmatization of mental health has shined light on negative mental health outcomes for minority communities in the United States. Literature has found that the Latinx community faces diminished mental health due to social, political, and economic pressures, and furthermore the need for additional investigation into mitigation tactics of this discrepancy. This analysis first describes five factors which impact mental health of the Latinx community: mental health literacy, stigma surrounding mental health, acculturative stress, discrimination, and financial stress. As young adulthood is pivotal in an individual’s mental health trajectory, the paper describes the study which aims to understand the psychological stress Latinx college students experience as compared to their white counterparts at a prestigious university in the United States. Participants included 67 students from Duke University who voluntarily participated in an online survey including the full Brief Symptom Inventory (BSI). Results in this study found no statistically significant difference amongst BSI and Global Severity Index (GSI) scores of Latinx and White participants. Additionally, no statistical significance was found in the difference between Latinx and White participant anxiety and depression dimension scores. It is critical to understand the role that cultural and racial identity plays in Latinx mental health and minority mental health as a whole. The null findings of this study serve to inspire further investigation to understand the mental health state of Latinx individuals in their young adulthood, and what role their educational environment plays in their psychological stress levels.Item Open Access Microglial MyD88 Dependent Pathways are Regulated in a Sex Specific Manner in the context of HMGB1 induced anxiety(2024) Rawls, AshleighStress exposure is the most cited factor in the development of both anxiety and depressive disorders. Both anxiety and depressive disorders have an increased prevalence in females; however, capturing this using pre-clinical models of stress has proven to be challenging. Therefore, we employed High Mobility Group Box 1 (HMGB1), an established pharmacological model of stress. Using this model, we sought to investigate the mechanisms which underlie HMGB1 associated behavioral changes in both male and female mice. Previous work demonstrated that circulating HMGB1 throughout the brain via the third ventricle causes depression like behavioral changes decreased sucrose preference, decreased sucrose consumption, decreased social preference, and increased immobility in the tail suspension test. Due to the known role of the cortico-limbic circuit in depression, we hypothesized that infusion of HMGB1 directly to the medial Prefrontal Cortex (mPFC) would also cause a depressive-like phenotype previously reported. Alternatively, we observed changes strongly associated with an anxiety-like phenotype. Previous work has implicated HMGB1 in chronic and acute stress responses; however, a majority of CNS cell types express receptors for HMGB1. Extracellular HMGB1 signals like a cytokine binding to many receptors that participate in pro-inflammatory signaling; yet a cell specific role for microglia the resident immune cell of the brain has not been clearly delineated. HMGB1’s effect on behavior has been causally linked to the activation of both RAGE and TLR4 pathways. Both pathways rely on concurrent activation of Myeloid differentiation primary response 88 (MyD88), though MyD88 independent activation is possible. We hypothesize that microglia reactivity is a necessary mechanism by which HMGB1 alters behavior and in this context increases anxiety. Moreover, we posit that MyD88 may be critical to increased microglial reactivity in response to HMGB1. To test this hypothesis, we utilized a pharmacological model of stress whereby dsHMGB1 was administered locally to the mPFC via cannula. Both male and female mice, aged 12-20 weeks, underwent stereotaxic surgery for the implantation of an intracerebral ventricular (ICV) guide cannula into the left medial prefrontal cortex. After a recovery period, mice were infused with artificial cerebrospinal fluid (aCSF) or recombinant HMGB1 (dsHMGB1) for five consecutive days. Following dosing, behaviors related to anxiety, despair and sociability were assayed. Various behavioral tests were conducted, including the Open Field Test (OFT), Elevated Plus Maze (EPM), Social Preference Assay, Novelty Suppressed Feeding (NSF), Home cage Feeding Assay, Light Dark Box (LDB) test, and Tail Suspension Test (TST). Baseline weights were established, and daily weight measurements were taken before and during dosing periods. Weight changes were calculated from baseline. To determine if female behavioral changes were also correlated with estrus vaginal cytology was performed to determine the stage of the estrous cycle. Smears were obtained and stained using the hematoxylin-eosin method, with cell types counted to define each stage of the cycle. We found that both male and female mice showed increased anxiety-like behavior in the EPM and Home cage Feeding Assay. For females specifically, we found that dsHMGB1 treatment caused significant changes in weight and that neither the behavioral phenotypes nor changes in weight were correlated with estrus cycle changes. Understanding the importance of microglial reactivity in stress response, we sought to evaluate microglial functional alterations in response to HMGB1. 16 hours after the final dose of dsHMGB1 or aCSF, mice were perfused and brain sections containing the medial prefrontal cortex were processed for immunohistochemical staining. Fluorescent images were captured for analysis of microglial activation. Microglia were reconstructed individually in IMARIS software and measurements for volume and branching were taken. We found that male and female demonstrated similar alterations in morphology wherein dsHMGB1 reduced the average number of Sholl intersections in more distal parts of the microglia. Though we again observed female specific effects relative to changes in Iba1 volume, ratio of TMEM119:Iba1 volume, and phagocytic index. Overall dsHMGB1 alters morphology of microglia indiscriminately of sex but additional changes related to reactivity were only observed in female mice. HMGB1 is recognized by multiple receptors including RAGE and TLR4 and activation of these receptors is often dependent on the concurrent activation of other adaptor proteins like MyD88 and TRAF6. Microglial RAGE, microglial TLR4, and MyD88 have been previously shown to be necessary mediators of neuroinflammatory stress responses. In this model, we determined the manner in which HMGB1 alters transcriptional activity of these key signaling molecules. Mice underwent the previously outlined surgery, recovery, and dosing timeline. 16 hours after the final dose of either aCSF or dsHMGB1 was administered, mice were sacrificed, and frontal cortex was removed using microdissection techniques. We utilized a cell specific isolation protocol to separate microglia and non-microglia cells by their expression of CD11b. RNA was extracted from these two populations of cells, and cDNA synthesis was performed. Quantitative real-time PCR (qPCR) was conducted to assess gene expression related to HMGB1-dependent signaling pathways. We found that female mice showed a robust pro-inflammatory phenotype defined by increased expression of both RAGE and MyD88 in microglia as well as increased MyD88 in non-microglial cells. For males, no significant changes in transcriptional activity were observed; however, it is of note that the directionality of male expression in the HMGB1 treated group is opposite of that seen in females. Together the data thus far established that HMGB1 exerts functional alterations in microglia in both sex specific and sex indiscriminate ways. We hypothesized that MyD88 specifically in microglia could be a key factor in conferring stress induced behavioral changes. To test this, we employed a transgenic mouse line with conditional deletion of MyD88 (cKO mice) in microglia. We utilized the surgery, recovery, and dosing timeline previously outlined to investigate anxiety-related behaviors. We found the female cKO mice did not show increased anxiety-like behavior following HMGB1 infusion and that male cKO mice did show increased anxiety-like behavior in response to HMGB1. This demonstrates that microglial MyD88 is necessary for HMGB1 induced anxiety in adult female mice. Taken together, the primary aim of this work is to examine the mechanisms of HMGB1 induced behavioral changes in a cell specific manner in both sexes. We found that HMGB1 acts on microglial cells in the context of anxiety as measured by changes in transcriptional changes, morphology, and phagocytic activity. Surprisingly, female but not male mice demonstrate concurrent changes in microglial reactivity and pro-inflammatory associated transcriptional changes. Specifically, female microglia show increased phagocytic capacity and decreased TMEM119 volume relative to Iba1, evidence of dysregulated homeostasis. Moreover, both RAGE, a putative HMBG1 receptor, and the adaptor molecule MyD88 were increased following dsHMGB1 in the microglia isolated from mPFC. Finally, we determined if microglial MyD88 conditional knockout (cKO) mice demonstrate a unique behavioral phenotype following dsHMGB1 infusion to the mPFC. These data appear to demonstrate that female mice rely on microglial mediated activation of MyD88 to respond to increased HMGB1 in the mPFC, whereas males do not. Without microglial MyD88, females do not demonstrate an anxiety-like response following dsHMGB1 administration whereas cKO males continue to show HMGB1-induced behavioral changes. Taken together these data elucidate a role for microglia in HMGB1 mediated behavioral responses. Furthermore, we have identified a potential sex-specific microglial mechanism of action underlying the impact of HMGB1 on behavior.
Item Open Access Microinterventions targeting regulatory focus and regulatory fit selectively reduce dysphoric and anxious mood.(Behav Res Ther, 2015-09) Strauman, Timothy J; Socolar, Yvonne; Kwapil, Lori; Cornwell, James FM; Franks, Becca; Sehnert, Steen; Higgins, E ToryDepression and generalized anxiety, separately and as comorbid states, continue to represent a significant public health challenge. Current cognitive-behavioral treatments are clearly beneficial but there remains a need for continued development of complementary interventions. This manuscript presents two proof-of-concept studies, in analog samples, of "microinterventions" derived from regulatory focus and regulatory fit theories and targeting dysphoric and anxious symptoms. In Study 1, participants with varying levels of dysphoric and/or anxious mood were exposed to a brief intervention either to increase or to reduce engagement in personal goal pursuit, under the hypothesis that dysphoria indicates under-engagement of the promotion system whereas anxiety indicates over-engagement of the prevention system. In Study 2, participants with varying levels of dysphoric and/or anxious mood received brief training in counterfactual thinking, under the hypothesis that inducing individuals in a state of promotion failure to generate subtractive counterfactuals for past failures (a non-fit) will lessen their dejection/depression-related symptoms, whereas inducing individuals in a state of prevention failure to generate additive counterfactuals for past failures (a non-fit) will lessen their agitation/anxiety-related symptoms. In both studies, we observed discriminant patterns of reduction in distress consistent with the hypothesized links between dysfunctional states of the two motivational systems and dysphoric versus anxious symptoms.
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