Browsing by Subject "anxiety"
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Item Alexithymia subscales have distinct roles in both the variability of arousal ratings and in associations with anxiety and psychological inflexibility(2022-11) Knauz, SaraAlexithymia is a subclinical cluster of deficits in emotional processing prevalent across a wide variety of clinical populations. One alexithymia component, difficulty identifying feelings (DIF), appears the most related to both distress and treatability. Unfortunately, effects of alexithymia on important variables remain inconclusive, including subjective emotional arousal ratings, arousal-relevant clinical symptoms, and risk factors for mental illness. We proposed that this inconclusiveness was due partly to differences across alexithymia models and questionnaires. In a behavioral study (N=241), participants provided emotional arousal ratings of stimuli paired by verbal label and core affect, and questionnaire responses. We computed rating variability as difference scores between paired stimuli. High alexithymia and DIF increased variability of arousal ratings, and generalized anxiety increased both ratings and their variability, but only for low-arousal stimuli. The strongest effects involved another alexithymia subscale, Difficulty Emotionalizing (DE), which decreased both emotional arousal ratings and rating variability for low-arousal stimuli. These findings are consistent with the theory that strong situations can overshadow differences in behavior, while weaker situations reveal both individual differences and intraindividual variability. Intriguingly, DE also decreased ratings of high-arousal stimuli, superseding the strong situation. Because DE affected behavior more than DIF, DE and the heterogeneity of alexithymia warrant further study. In a large study (N=1977), respondents completed questionnaires for alexithymia; anxiety; and psychological inflexibility, including cognitive fusion. In the two most common alexithymia questionnaires, we replicated aspects of the construct’s structure, including common subscales and higher-order dimensions, and extended them to the newer Perth Alexithymia Questionnaire. Based on psychometric properties we found and computed, we recommend when to choose a given alexithymia questionnaire. In regression models, the concurrence of anxiety and psychological inflexibility consistently predicted alexithymia, especially DIF. Moderations suggested psychological inflexibility may contribute to the development of alexithymia in individuals with anxiety symptoms. Even at subclinical levels of anxiety, anxiety’s interaction with experiential avoidance may lead to alexithymia. Individuals with clinical levels of generalized anxiety and high cognitive fusion may be at risk for increased DIF. Individuals high in both social anxiety and psychological inflexibility may have clinical distress related to Difficulty Identifying Negative Feelings.Item Anxiety and Depression: What if I have both?(2009-09-18) Ho, Sing-WeiThe addition of a benzodiazepine to an SSRI provides more rapid global improvement of generalized anxiety disorder and depression than an SSRI alone. Patients are less likely to discontinue treatment and more likely to show improvement than those receiving antidepressant monotherapy. In addition, the risks of benzodiazepine abuse are low outside of the setting of polysubstance abuse. Overall, patients with co-existing depression and anxiety should be treated in the initial few weeks with combination therapy to prevent premature drop-out from treatment.Item Association between Temporomandibular Disorders Pain, Oral Behaviors, Anxiety and Stress(2019-03) Thakur, PreetanjaliAims: Oral behaviors, anxiety and stress are believed to be related to temporomandibular disorders (TMD) pain. The aims of the study were to investigate the association of TMD pain intensity with oral behaviors, anxiety and stress, and the association of oral behaviors with anxiety and stress. Methods: From among the clinical and community-based participants in the multi-site Validation Project, 721 subjects were included in this study who had completed self-report questionnaires that reported pain intensity (Characteristic Pain Intensity [CPI]), oral behaviors (Oral Behavior Checklist [OBC]), anxiety (Symptom Checklist - 90 revised [SCL-ANX]) and stress (Perceived Stress Scale [PSS]) experienced during the previous month; and anxiety experienced during the previous week. Participants were divided into four groups based on the CPI report: no pain, mild, moderate and severe pain, and were compared using analysis of variance (ANOVA). Statistical differences between groups were evaluated using an F-test for continuous variables and Chi-square test for categorical variables. Spearman correlation coefficients were computed to examine the association of (1) CPI with OBC, SCL-ANX and PSS and (2) OBC with SCL-ANX and PSS. Simple linear regression analysis was used to investigate the bivariate relationships for outcomes CPI and OBC. The multivariate regression analysis with age and sex adjustment was conducted to examine relationship between CPI and dependent variables, and OBC and dependent variables. Results: Using CPI as a categorical variable, pain intensity was associated by a dose-response curve relationship for each of the independent variables: OBC, SCL-ANX, and PSS (ANOVA; p<0.0001). Positive correlations were found between CPI versus OBC (r=0.44, n=721), SCL-ANX (r=0.30, n=720), and PSS (r=0.21, n=721) with p<0.0001 for all correlations. Positive correlations between OBC with SCL-ANX (r=0.38, n=720) and PSS (r=0.32, n=721) with p<0.0001 were found. Using simple linear regression, OBC accounted for 18% of the variance of CPI versus SCL-ANX and PSS that explained 10% and 5% of CPI, respectively. SCL-ANX and PSS accounted for 12% and 11% of the variance of OBC, respectively. The multivariate regression model estimated that with 1SD increase of OBC, CPI will increase by 9 after adjusting for SCL-ANX, PSS, age and gender. For 1 SD increase in SCL-ANX, CPI will increase by 5 after adjusting for OBC, PSS, age and gender. For 1 SD increase in SCL-ANX, OBC will increase by 2.27 and for 1 SD increase in PSS, OBC will increase by 1.63 after adjusting for age, sex and each other. These statistically significant associations are positive and range from weak-moderate with correlation coefficients of 0.21 to 0.44. Together, these variables with age and sex adjustment explain 22% of the TMD pain intensity variability. Together, anxiety and stress with age and sex adjustment explain 19% of the variability of oral behaviors. Conclusion: Participants with severe TMD pain intensity reported significantly higher frequency of oral behaviors and higher levels of anxiety and stress compared to participants with no and mild pain. Participants with higher frequency of oral behaviors reported significantly higher anxiety and stress compared to participants with lower frequency of oral behaviors. Participants with the highest frequency of oral behaviors (tercile III of OBC) had clinically significantly more TMD pain than those with the lowest frequency of oral behaviors (tercile I of OBC). As predicted by the biopsychosocial model, TMD pain is associated with many factors beyond those assessed in the present study.Item Associations Between Maternal Anxiety, Infant Attention and Amygdala Development in the First Three Years of Life(2024-07) Lasch, CarolynThe overarching aim of this dissertation was to better understand how socially salient information biases rapid visual orienting in infants and toddlers, and if this bias is associated with other early correlates of later anxiety diagnoses, including infant temperament, maternal anxiety, and amygdala volume. This study represents an important contribution to the literature focused on early development of attention biases and their associations with later anxiety, especially as it incorporates measures of neurodevelopment, caregiver psychopathology, and infant temperament to better understand overlapping and interacting risk factors for later-emerging anxiety. Both aims primarily utilize a sample of data from the Baby Connectome Project, taking advantage of accelerated longitudinal sampling to characterize attention orienting and amygdala development in the first three years of life. Aim 1 decomposed traditional measures of attention orienting bias into two separate measures (attention facilitation and orienting cost) to more precisely examine how socially salient stimuli such as fearful faces relate to vigilance and orienting in early development, and how visual competition may moderate these biases. Associations between early correlates of anxiety (infant temperament and maternal anxiety) and orienting biases were also examined. Findings indicated some unexpected associations, mainly reduced biases in infants with more anxious temperaments, and in infants with higher-anxiety mothers. Findings also highlighted the degree to which stimuli in “competition with” (i.e., co-presented with) fearful stimuli can moderate orienting biases for infants with and without early risk factors for attention biases and anxiety. Aim 2 examined if and how attention orienting biases (attention facilitation and orienting cost), infant temperament, and maternal anxiety were reflected in right amygdala volume development in the first three years of life. Findings revealed that infant mean reaction time (but not attention biases scores) was associated with right amygdala volumes, such that infants with slower reaction times showed more rapid amygdala volume growth. Additionally, infant and toddler temperament were associated with larger right amygdala volumes over the 0- to 3-year period. These findings highlight very early associations between temperamental risk factors for later anxiety and altered neurodevelopment in regions associated with later anxiety. Taken together, these findings suggest that early risk factors for anxiety (especially infant temperament) have early-emerging associations with biased attention orienting and atypical neurodevelopment. Future studies are needed to extend these findings by examining possible complimentary effects in the right visual hemifield, investigating attention orienting biases in later developmental periods, and further elucidating possible associations between infant attention orienting biases and amygdala resting-state functional connectivity.Item Deciding Which Fears to Face: Behavioral and Neural Mechanisms of Costly Avoidance in Clinical Anxiety(2022-07) Berg, HannahClinical anxiety is often characterized by a behavioral pattern of relinquishing rewards in order to avoid potential threats, a decision-making bias that confers substantial functional impairment. However, the mechanisms of such costly avoidance have received scant attention in the literature. The present work addresses this gap, applying fear-conditioning methodology and functional magnetic resonance imaging (fMRI) to probe the neural and psychological processes contributing to costly avoidance. A sample of 153 adults with and without clinical anxiety underwent fMRI while completing a fear-conditioning and generalization paradigm in which participants decide between risky approach and costly avoidance. Anxious individuals were more likely than others to make costly, unnecessary avoidance decisions in the context of generalized Pavlovian fear, as has been seen previously. Subsequent analyses provide novel insights into this finding. When assessing risk and reward appraisals, anxious individuals demonstrated a greater likelihood of avoidance in the context of moderate expected risk or low expected reward. Brain-wide correlations and multivariate pattern analyses revealed that neural activity during choice deliberation in regions associated with cognitive control, sensory processing, and perception-motor integration scaled with risk and reward appraisals and was predictive of choice. Among anxious individuals, however, these neural processes were less correlated with expected risk and were less predictive of choice, suggesting that the observed avoidance bias may stem from a relatively weak formation of a prepotent approach response, and for a tendency to second-guess or ignore the results of deliberative valuation. Taken together, the present findings represent a significant advance in the conceptualization of costly avoidance in clinical anxiety.Item Effectiveness and Key Components of School-Based Anxiety Interventions(2019-05) Erhardt, VictoriaAnxiety disorders and subclinical anxiety symptoms are prevalent in childhood and adolescence, highlighting the need for prevention and early intervention efforts. While research has demonstrated positive effects for some school-based anxiety interventions, additional research is warranted to ascertain program effectiveness, composition, and delivery to best meet student needs. This multi-study dissertation project comprised of two studies. Study 1 was a systematic literature review that examined anxiety interventions for youth in school settings and updated and expanded a previous systematic review (Neil & Christenson, 2009) to more fully understand the state of the science regarding school-based anxiety programs. Randomized controlled trials (RCT) from articles published between 2008 and June 2016 were reviewed and evaluated in areas including program effectiveness, program content, intervention intensity, and participant age. Twenty-two RCTs, representing 9,693 study participants, were coded and analyzed. Results indicated that 43% of trials reported statistically significant reductions in anxiety (ES = -0.69 to -0.15) with the majority of programs based in cognitive behavioral therapy (CBT). Results from Study 1 were used to inform the development and implementation of an applied school-based anxiety intervention. In Study 2, Think Good Feel Good was implemented as a low-cost, 6-week, CBT-based modularized intervention to address student anxiety in an elementary school utilizing a multiple-baseline single case design. The main purpose was to analyze the effectiveness of the program as measured by formative and summative anxiety assessment measures following a multi-method, multi-source approach. Participants included 14 students across third, fourth, and fifth grades at a public elementary school. Results of the study indicated both responders and non-responders to the intervention. Self-report data on the Multidimensional Anxiety Scale for Children (MASC-2) pre/post assessments showed statistically significant anxiety reduction on the generalized anxiety disorder and the physical symptoms scales, whereas parent and teacher pre/post data and progress monitoring data revealed mixed findings. Social validity data from students indicated high acceptability and perceived utility. The implications of the results from this dissertation project for future research and practice are discussed.Item Molecular mechanisms and therapeutic potential of inhibitory G protein signaling in anxiety disorders(2020-08) Vo, BaoviAnxiety disorders are common and debilitating. Current medications for treating anxiety disorders carry addictive potential and have adverse side effects, highlighting the need for improved therapeutics. Several commonly prescribed drugs used to treat anxiety disorders enhance inhibitory G protein signaling in neurons, leading to the modulation of multiple enzymes and ion channels. The relative contributions of these individual G protein-regulated effectors to anxiety-related behavior are unclear. My thesis research focuses on one such effector – the G protein-gated inwardly rectifying K+ (GIRK) channel. GIRK channels mediate the postsynaptic inhibitory effect of GABA and other inhibitory neurotransmitters in the central nervous system. There are 4 GIRK subunits (GIRK1-4). Neuronal GIRK channels typically contain GIRK1 and GIRK2. Previous work from our lab found that the GIRK channel activator (ML297), which shows a slight preference for GIRK1/2 channels, reduces anxiety-related behavior in mice without exhibiting addictive potential. My central hypothesis is that activators of the GIRK1/2 channel subtype could treat anxiety-related disorders. My thesis explored three interrelated questions: Which brain regions and neuronal populations underlie the influence of GIRK channels on anxiety-related behavior? While ML297 reduces anxiety-related behavior in mice, the relevant brain regions and neuron populations underlying this effect were unclear. I utilized pharmacologic and viral genetic approaches to manipulate GIRK-dependent signaling in distinct neuron populations in the ventral hippocampus (vHPC) and the basolateral amygdala (BLA), and evaluated the impact of these manipulations on anxiety-like behavior using the elevated plus maze (EPM) test. Intra-vHPC ML297 reduced anxiety-related behavior, akin to the effect observed with systemic ML297. In contrast, ML297 infusion into the BLA increased anxiety-related behavior in the EPM. Chemogenetic neuron-specific manipulations revealed neuronal subtypes within vHPC and BLA mediate these effects. These findings could inform targeted treatments for anxiety-related disorders. Do GIRK channel activators have anxiolytic therapeutic potential? Despite the promise of ML297 in studies of anxiety-related behavior, its modest selectivity for neuronal channels, its poor in vivo stability, and its limited ability to penetrate the blood-brain barrier preclude its clinical utility. I characterized a new GIRK channel activator, VU0810464, which showed improved brain penetration and enhanced selectivity for GIRK1/2 channels. I also demonstrated its in vivo efficacy in the stress-induced hyperthermia test. VU0810464 is a new, important tool for investigating the relevance of GIRK1/2 channels in physiology and behavior. What factors influence GIRK-dependent signaling? The GIRK2 subunit is necessary for neuronal GIRK channel function and has three distinct splice variants that have not been extensively characterized. I demonstrated the influence of these splice variants on three different GIRK-dependent signaling pathways in cultured hippocampal neurons using an electrophysiological approach. We found that these GIRK2 splice variants differed in their subcellular distribution, and this difference impacted their contribution to the processing of inhibitory input and to fear learning behavior. This knowledge provides insight into a key element influencing GIRK channel function, and importantly, opens more opportunities for future studies targeting GIRK-dependent signaling for therapeutics. In brief, I present a body of work in this thesis that contributes to the field’s knowledge of GIRK-dependent signaling and offers the potential for novel treatment for anxiety-related disorders.Item Normative and Pathological Personality Predictors of Generalized Conditioned Fear, Instrumental Avoidance, and the Covariation of Generalized Fear and Avoidance(2019-08) Cooper, SamuelMechanistic conditioning models of human anxiety pathology have established overgeneralization of classically conditioned fear as a maladaptive correlate of clinical anxiety (e.g., anxiety disorders). These models have also, until recently, largely discounted the pathological contribution of instrumental avoidance of feared stimuli. This is in stark contrast to clinically-based models of anxiety pathology, which establish that the most severe forms of clinical anxiety involve excessive avoidance that results in loss of valued activity and opportunity to extinguish fear, and links this avoidance to individual differences in a variety of personality traits. Recent mechanistic work has partially addressed this gap and investigated the relationship between generalized fear and generalized avoidance, but has largely not incorporated individual difference variables. The current investigation furthers the merging of mechanistic conditioning and clinical models in this area by testing how broadband individual differences (e.g., personality traits) ranging from normative to pathological can improve prediction of instrumental avoidance from generalized fear. Candidate personality variables include those related to Conscientiousness and Extraversion, both traits that are linked to learning and approach systems. The method for this investigation involved lab-based assessment using established conditioning paradigms with behavioral and psychophysiological indicators, as well as multidimensional self-report inventories and a multilevel modeling analytic approach to facilitate more precise testing of personality-related hypotheses. Results indicate that 1) multiple measures of pathological negative affect are related to increased fear generalization and facilitate a maladaptive fear-avoidance relations; 2) Extraversion-related variables generally buffer against fear-avoidance covariation, whereas pathologically low Extraversion (detachment) facilitates the fear-avoidance relation; 3) Conscientiousness-related variables both facilitate and inhibit the fear-avoidance relation, depending on context; and 4) the relationship between the personality variables, generalized fear, and avoidance depends partially on how the fear metric is operationalized (e.g., physiologically or behaviorally). These results are discussed within a framework of improving methodology for future investigations that combine conditioning and individual differences approaches and, eventually, using this type of work to inform translational efforts to further refine and personalize treatments for anxiety and trauma-related psychopathology.Item An Online Mindfulness Intervention to Reduce Stress and Anxiety Among College Students(2015-08) Greer, ChristiaanThis study evaluated the efficacy of two different web-based stress management programs among college students at a large Midwestern university. After completing the pretest, students (N = 401) were randomly assigned to a Mindfulness plus Present Control intervention, a Mindfulness only intervention, or a Stress-information only comparison group. Primary outcomes were stress, anxiety, depression, perceived stress and worry; hypothesized mediators of intervention efficacy were rumination, mindfulness and present control. Self-report measures were completed online at pre-intervention, post-intervention, first follow-up (2-3 weeks postintervention) and second follow-up (4-5 weeks postintervention). Ninety percent of the sample (n = 365) completed the pretest and comprised the intent-to-treat sample. Linear mixed modeling was used to assess significant change over time and hierarchical regression was used to test for mediation. Participants in all three groups reported significant decreases in all five primary outcomes across all time points (within group d's = -.15 to -.56). All time by intervention group interaction effects were non-significant suggesting that the three conditions were equally effective. With regard to the mediators, participants reported significant increases in present control and mindfulness and significant decreases in rumination from baseline to post-intervention and both follow-ups (within group d's = .01 to .71). There was one significant time by intervention group interaction effect in the analyses assessing change over time in the mediators specifically indicating a between-group difference in changes in rumination, F(8, 973) = 3.73, p = .0003. In this case, the Mindfulness plus Present Control group reduced rumination significantly more than the comparison group. Because there were few differences across conditions, mediation analyses were performed collapsing across conditions. In general, changes in present control were associated with changes in depression and changes in rumination were associated with changes in worry and perceived stress at the second follow-up controlling for baseline scores. Limitations and future direction are discussed.Item Spirits in distress: Converging plasticity of ventral tegmental area (VTA) gamma amino-butyric acid (GABA) neurons evoked by chronic ethanol and stress controls anxiety symptomatology(2024-07) Mitten, EricThe ventral tegmental area (VTA) and associated signaling has been historically implicated in reward evaluation and seeking. Due to this, dysfunction of the VTA has been largely linked to substance use disorders, including alcohol use disorder (AUD). Recent evidence has also identified a role of the VTA in stress-related anxiety disorders, highlighting its diverse functional role. The majority of work in this structure has focused on dopaminergic (DA) neurons, as well as associated DA release. However, the VTA is host to a variety of neuron populations defined by neurotransmitter content, including gamma amino-butyric acid (GABA)- releasing neurons. Existing evidence positions VTA GABA neurons as potent regulators of anxiety, fear, and aversion through regulation of neighboring VTA DA neurons as well as discrete long-range projections. Lines of evidence indicate that VTA GABA neurons exhibit enhanced activity following chronic ethanol or stress exposure. Therefore, the goals of this dissertation were to further identify plasticity evoked in VTA GABA neurons in these contexts that could contribute to enhanced activity and determine the functional role of VTA GABA neuron plasticity within these disease states. Ethanol's effects in the central nervous system and the expression of AUD has been extensively linked to plasticity in GABAergic signaling, including presynaptic GABA release and postsynaptic GABAA receptors (GABAAR) and GABAB receptors (GABABR). Moreover, G- protein gated inwardly-rectifying K+ (GIRK) channels, a primary effector of GABABR signaling, also plays a critical role in the context of AUD. While it has been partially assessed, sites of GABAergic signaling plasticity evoked by chronic ethanol in VTA GABA neurons have yet to be thoroughly assessed. In Chapter 2, we utilized slice electrophysiology to identify several forms of GABAergic plasticity. Firstly, VTA GABA neurons exhibit a significant reduction in presynaptic GABA release that was dependent on the action of GABABR's, implicating plasticity in GABABR-dependent presynaptic regulation of GABA release. We surprisingly found no effect in GABAAR- dependent currents, suggesting that postsynaptic GABAAR signaling may be largely unaffected. On the other hand, postsynaptic GABABR/GIRK-dependent currents were significantly diminished, which was found to be associated with increased intracellular localization of the GABABR1 subunit as well as GIRK2. Utilizing a constitutive knockout approach as well as VTA GABA specific CRISPR/Cas9 mediated ablation, we identified GIRK3 as necessary for this plasticity in postsynaptic GABABR/GIRK signaling. These data, in conjunction with existing evidence, suggest that GABAergic signaling plasticity in VTA GABA neurons following chronic ethanol exposure could contribute to the expression of symptoms associated with AUD. Utilizing VTA GABA specific CRISPR/Cas9 mediated ablation of GIRK2, we found that loss of GABABR/GIRK currents was sufficient to induce anxiety symptomatology, suggesting a role of VTA GABA neurons in ethanol withdrawal-induced anxiety. Stress has been demonstrated to increase the activity of VTA GABA neurons, as well as evoke plasticity that suggests VTA GABA neurons exhibit enhanced excitability. Interestingly, enhanced activity of VTA GABA neurons is required for restraint stress-induced anhedonia, suggesting a role of VTA GABA neurons in other stress-induced affective symptoms. In Chapter 3, we utilized an unpredictable footshock (uFS) protocol to assess the effect of stress on VTA GABA neurons due to its ability to reliably evoke anxiety symptomatology. uFS was sufficient to enhance the excitability of VTA GABA neurons, as assessed via increased baseline firing, increased input resistance, and decreased rheobase. Furthermore, this hyperexcitability was associated with enhanced presynaptic glutamate release, as well as diminished postsynaptic GABAAR and GABABR signaling, suggesting that stress evokes several mechanisms of intrinsic and extrinsic plasticity of VTA GABA neurons. Utilizing a chemogenetic approach, we found that enhanced excitability of VTA GABA neurons in behaviorally-naïve mice was sufficient to evoke anxiety, while diminishing excitability of VTA GABA neurons was sufficient to block the expression of uFS-induced anxiety. These data posit that VTA GABA neuron excitability is necessary for stress-induced affective symptomatology, suggesting that VTA GABA neuron dysfunction may underlie disorders associated with this symptomatology. Altogether, this work contributes to a growing body of evidence identifying the functional role of VTA GABA neurons, as well as provides insights into novel therapeutic targets for the treatment of anxiety in the context of AUD and stress-related anxiety disorders. Furthermore, this work positions VTA GABA neurons as an overlapping site of plasticity between chronic ethanol and stress that could contribute to reciprocal exacerbation of each disease state.