PHD, Kent State University, 2016, College of Arts and Sciences / Department of Psychological Sciences

Anxiety disorders are the most common mental disorder with nearly 30% of individuals meeting criteria for an anxiety disorder over the course of their lifetime, generating significant personal, financial and emotional burden. Additionally, women are 60% more likely than men to be diagnosed with an anxiety disorder, such as PTSD. Inappropriate fear that occurs in normally safe environments, or fear generalization, is a key symptom of many anxiety disorders. The current set experiments explores sex differences in the generalization of fear and identifies mechanisms by which estradiol affects fear generalization. Results demonstrate that females generalize fear at a faster rate than males, and this process is driven, in part, by estradiol. However, in males, estradiol acts to attenuate generalization rather than to induce generalization. In fact, testosterone also attenuates generalization in gonadectomized males and does so through conversion into estradiol via aromatase. Estradiol impacts generalization through effects on memory retrieval rather than memory acquisition/consolidation. In females, estradiol acts through activation of cytosolic ERß within the dorsal CA1 region of the hippocampus and the anterior cingulate cortex (ACC), but not the ventral CA1 region of the hippocampus. Finally, estradiol-induced generalization in females appears to be a result of augmented glutamatergic signaling within the dorsal CA1 and ACC; blocking glutamate receptor activation attenuates estradiol-induced generalization. These mechanisms can help explain the discrepancies in prevalence rates for anxiety disorders between males and females, and are also crucial for development of more effective, and potentially sex-specific, treatments for anxiety disorders such as PTSD.

Committee: Aaron Jasnow Ph.D (Advisor); David Riccio Ph.D (Advisor); Stephen Fountain Ph.D (Committee Member); Karin Coifman Ph.D (Committee Member); John Johnson Ph.D (Committee Member); Heather Caldwell Ph.D (Committee Chair) Subjects: Animals; Behavioral Psychology; Biology; Endocrinology; Experimental Psychology; Neurobiology; Pharmacology

Doctor of Philosophy (PhD), Ohio University, 2017, Clinical Psychology (Arts and Sciences)

Negative interpretations of ambiguously threatening stimuli and over-generalized fear responding to benign situations are important cognitive mechanisms in the etiology and maintenance of anxiety-related disorders (e.g., Hirsch & Mathews, 2000; Lissek et al., 2008). These cognitive abnormalities may derive from over-active associative cognitive processes and under-active executive processes. Overarching assumptions of transdiagnostic cognitive phenomena have been proposed within the field of anxiety pathology. However, these assumptions have been largely based on disorder-specific studies, using disorder-specific stimuli. The current study: (a) implemented a novel transdiagnostic task to measure threat interpretation and fear response; and (b) tested the relations between over-generalized fear responding and trait anxiety severity. In addition, relations between executive functioning performance and threat interpretation styles were explored. Participants were 64 undergraduates (72% female, 80% Caucasian). Results indicated that high trait anxious individuals exhibited fear over-generalization, evidenced by higher perceived threat of benign stimuli and greater difficulty in stimulus discrimination over time, compared to low anxious individuals. High trait anxious individuals also responded faster to stimuli—suggesting less involvement of executive processing in potential threat response. However, counter to hypothesis, high and low anxious participants demonstrated similar skin conductance response throughout the task. Preliminary exploratory analyses indicated that trait anxiety was not significantly related to executive functioning performance. Cognitive flexibility was related to higher accuracy in threat perception, but lower accuracy for ambiguous stimuli. Also, response inhibition and concept detection/description were related to faster responses to the stimuli. The current results provide additional support for transdiagnostic abnormalities in fear learning a (open full item for complete abstract)

Committee: Julie Suhr Ph.D. (Committee Chair) Subjects: Clinical Psychology

PHD, Kent State University, 2013, College of Arts and Sciences / Department of Psychological Sciences

Contextual fear conditioning involves pairing a novel context (conditioned stimulus) with several footshocks (unconditioned stimulus) that serve to condition fear to that context. As the retention interval between training and testing increases context specificity is lost. In other words, the fear memory is no longer precise or context-specific, but has generalized to novel contexts at remote time points. In an attempt to investigate the neural pattern of an imprecise contextual memory trace as a function of time, we used fluorescent in situ hybridization to for Arc mRNA as a measure of neuronal activation following expression of a precise vs. imprecise context fear memory. Expression of a contextually precise memory involved increased Arc mRNA expression in both the dorsal and ventral CA1 regions of the hippocampus as well as the ACC and IL. Expression of a contextually imprecise fear memory involved Arc mRNA expression in the ventral CA1, ACC, IL, and the PL suggesting that both the hippocampus and prefrontal cortex are involved in the expression of a remote contextually imprecise memory. Further, inactivation of the ACC at remote time points returned the context memory to a precise state, but had no effect on memory for the training context. Taken together, these data suggest that as a context fear memory ages, both the hippocampus and prefrontal cortex interact in the expression of the memory trace resulting in the loss of precision. Preventing this interaction through inactivation of the ACC allows the hippocampus to express the contextually precise memory. In addition to the systems investigation of fear generalization, we also investigated a potential synaptic mechanism of the phenomenon. Specifically, we discovered that mice lacking a GABAB1 receptor subtype, GABAB1a, exhibit a loss of context discrimination compared to wild-type animals. Animals lacking GABAB1a receptors showed a significant, but not complete loss of context specificity 24 hours post-train (open full item for complete abstract)

Committee: David Riccio PhD (Advisor); Aaron Jasnow PhD (Advisor); Stephen Fountain PhD (Committee Member); Jeffrey Ciesla PhD (Committee Member); John Johnson PhD (Committee Member); Sean Veney PhD (Other) Subjects: Psychology

Master of Science (MS), Ohio University, 2008, Psychology (Arts and Sciences)

According to the fear-avoidance model, kinesiophobia (pain-related fear) is an important factor in the development of chronic pain and disability. The current research project investigated the extent to which expectancy corrections (i.e., the tendency to bring expected pain/harm in line with experienced pain/harm) following exposure to one movement generalize to identical movements of increased intensity in chronic low back pain patients with high versus low levels of kinesiophobia. Additionally, the study addressed the impact of increased exposure on generalization. Participants were asked to consecutively perform four adaptations of a reaching task, each introducing a discrete element of increased intensity. Expected and experienced pain and harm ratings were collected for each trial. It was predicted that highly kinesiophobic participants will demonstrate greater overprediction of pain and harm relative to their low-kinesiophobic counterparts. It is also predicted that in highly kinesiophobic participants, expectancy corrections evidenced in the later trials of a given movement will show less generalization to the subsequent movement performed.

Committee: Christopher R. France PhD (Committee Chair); Kenneth Holroyd PhD (Committee Member); Kathi Heffner PhD (Committee Member) Subjects: Psychology

MA, Kent State University, 2013, College of Arts and Sciences / Department of Psychological Sciences

Anxiety disorders are the most prominent mental disorder in the United States, and women are 60% more likely than men to have an anxiety disorder. One hypothesis for this sex difference is faster fear generalization rates in females. In previous studies using male subjects, context change disrupted a fear response at a short, but not long retention interval. An incidental observation suggested that females would show a different temporal pattern of fear generalization. In Experiment 1, male and intact female rats displayed disrupted fear responses in a novel context at 1 day. Males displayed context discrimination at all intervals, whereas females exhibited generalization by 5 days. In Experiment 2, ovariectomized females were given an empty capsule or a capsule containing 17ß-estradiol to determine the role of estrogens in fear generalization. Female rats with no hormone replacement displayed context discrimination at 5 days, whereas those receiving estradiol generalized their fear response to a novel context. These results demonstrate that fear generalization for contextual cues occurs faster in female rats and that this effect is mediated, in part, by estrogens. Understanding the sex differences in fear generalization is likely to be critical to developing effective treatments for anxiety disorders.

Committee: David Riccio (Advisor); Aaron Jasnow (Committee Member); Stephen Fountain (Committee Member); Beth Wildman (Committee Member) Subjects: Psychology