A relationship between schizophrenia and coeliac disease (CD) has long been postulated. However, despite the substantial genetic contribution defined for both conditions, the possibility of shared genetic risk factors has not previously been addressed. In this study, key CD-associated loci were tested in a schizophrenia cohort. Where association was found, functional studies were performed; including gene expression analysis, screening for functional variants, and correlation of alleles with antibody and cytokine levels. Two principle findings were drawn from the data produced. Firstly, there was no statistically significant association between schizophrenia, and the CD-associated loci; MY09B, IL-2/21, or HLA-DQ2. Secondly, a robust association was found for 3 SNPs located in the 5' region of the gene encoding TGM2; the gluten-modifying enzyme targeted by autoantibodies in CD. Functional studies provided evidence of decreased serum IL-2, in correlation with a schizophrenia-associated SNP located in the TGM2 gene. In addition, cell culture work showed altered expression of the TGM2 gene, following treatment with 1 I-Lg/ ml of the neuroleptic drug clozapine. This study concludes that the major genetic factors underlying schizophrenia and CD are distinct, and that the gluten response observed in schizophrenia does not follow the classical CD pathway. Furthermore, this study provides evidence of a novel candidate gene for schizophrenia, TGM2, and explores how it may contribute to neurological aspects of the disease.

The Tolerance/Intolerance of Ambiguity literature is plagued by conceptual confusion and methodological inadequacies. In particular, formulations of the construct and the instruments constructed to measure it suffer from a number of faults, including (1) incomplete and logically inconsistent definitions, (2) confusion regarding the relation between Tolerance/Intolerance of Ambiguity and Rigidity, (3) test confounds such as verbal ability and reactivity, (4) problems of item interpretation due to their verbal nature, (5) low estimates of internal consistency, and (6) questionable construct validity. In this study, a reconceptualization of Tolerance/Intolerance of Ambiguity was distinguished from the construct of Rigidity, and a non-verbal measure was developed which employs ambiguous figures as item stimuli and reaction statements as a response format for each item. Figural stimuli were utilized in order to circumvent confounding factors such as verbal ability, reactivity, and "fakeability." Analysis of 142 ambiguous figures yielded five categories which served as subscales of the test. After pilot testing and refinement, the psychometric properties of the resultant 30-item test, the Figural Measure of Ambiguity Tolerance (FMAT), were investigated by including it as part of battery of tests administered to high school, college, and university students (N=160). This battery included verbal and non-verbal tests of Authoritarianism, Intolerance of Ambiguity and Cognitive Ability chosen so as to allow for an evaluation of construct validity via examination of a Multi-Trait, Multi-Method correlation matrix. A second matrix, generated by adjusting for verbal and non-verbal Cognitive Ability, was also examined. In addition, a criterion-group referencing approach was used to examine construct validity. The Figural Measure of Ambiguity Tolerance showed evidence of good internal consistency reliability at the subscale and total scale levels. The a priori subscale structure was well-supported by factor-analytic results. Results of the validation portion of the study were inconclusive in that evidence of construct validity was minimal for all the measures involved. Given the limitations of previous conceptualizations and current verbal tests of Tolerance/Intolerance of Ambiguity, however, the results support the viability of this non-verbal measurement approach. / Education, Faculty of / Educational and Counselling Psychology, and Special Education (ECPS), Department of / Graduate

Intolerance of uncertainty (IU) has been proposed as an important transdiagnostic variable within various anxiety and mood disorders. It has been suggested that individuals high in IU may interpret ambiguous information in a more threatening manner. A parallel line of research has begun to show that interpretive biases can be modified through cognitive training. Specifically, previous research aimed at modifying negative interpretations through Cognitive Bias Modification (CBM-I) has yielded promising results. Despite the suggested negative interpretation bias for ambiguous information among those high in IU, and the emerging evidence for CBM-I protocols, no research to date has examined the efficacy of an IU focused CBM-I paradigm. The current study investigated the impact of a brief IU focused CBM-I on reductions in IU. The sample comprised 79 undergraduate individuals who were randomly assigned to the active (IU CBM-I) or control CBM-I condition. Results indicated no significant differences in IU in individuals in the control versus active condition from pre-intervention to one month follow-up. Furthermore, change in interpretation bias did not mediate the relationship between condition and reductions in IU (pre-intervention to one month follow-up) through change in interpretation bias. Exploratory analyses found a significant interaction between condition and time from pre- to post-intervention, suggesting that individuals in the active (versus the control) condition evidenced significantly lower IU from pre- to post-intervention. Results of the present study are discussed in terms of theoretical models of IU and directions for future research. / A Thesis submitted to the Department of Psychology in partial fulfillment of the Master of Science. / Spring Semester 2016. / April 5, 2016. / anxiety, interpretation bias, intolerance of uncertainty / Includes bibliographical references. / Norman B. Schmidt, Professor Directing Thesis; Jesse R. Cougle, Committee Member; Michael P. Kaschak, Committee Member.

Distress intolerance (DI) is a transdiagnostic individual difference variable reflective of the capacity to withstand aversive psychological states. DI is typically measured with self-report questionnaires or behaviorally via quit latency on distressing persistence tasks. Although both measurement methods have demonstrated predictive validity with respect to theoretically-related clinical problems, cross-method convergence of DI measures is generally not found, which may be due to the lack of theoretically-derived behavioral indicators of DI. Extant persistence tasks are face valid measures of DI, but they do not directly assess a theorized central feature of DI: the ability to inhibit prepotent responses to negative reinforcers under distress. The primary aim of the present study was to evaluate the relations between a novel behavioral measure of this ability (i.e., Negative-Escape stop-signal reaction time (SSRT) on a modified stop-signal task) and DI self-report/persistence measures as well as DI-linked clinical problems (i.e., perseverative thought, :coping motives for substance use, stress-elicited substance use problems) in a large non-clinical sample (N = 199). Consistent with most prior literature, self-report and persistence measures of DI were non-significantly correlated, but, contrary to predictions, Negative-Escape SSRT was also unrelated to DI and associated clinical problems. However, exploratory analyses revealed that DI measured via self-report but not task persistence was associated with faster reaction time (RT) on Go trials with negative reinforcement relative to neutral stimuli (i.e., facilitated ΔEscapeRT). Further, facilitated ΔEscapeRT was related to some DI-linked clinical problems (i.e., perseverative thought, depression coping motives for alcohol use) and moderated the effect of stressful life events on change in alcohol use-related problems over a one-month follow-up period. Theoretical and clinical implications are discussed. / A Dissertation submitted to the Department of Psychology in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2017. / June 6, 2017. / Includes bibliographical references. / Jesse Cougle, Professor Directing Dissertation; Heather Flynn, University Representative; Brad Schmidt, Committee Member; Walter Boot, Committee Member; Rick Wagner, Committee Member.

Background: Intolerance of uncertainty (IU) is a cognitive vulnerability implicated in the etiology and maintenance of pathological anxiety. Research has yet to examine IU during the course of treatment for anxious youth to inform whether IU may be an important construct to target to improve the effectiveness of available interventions. The current study evaluated whether IU mediates the relationship between anxiety severity pre- to post-treatment while controlling for levels of IU at pre-treatment. Methods: Participants were 69 youth aged 7 to 17 who participated in cognitive behavioral therapy (CBT) for anxiety. Youth and their caregiver(s) completed a diagnostic interview administered by an Independent Evaluator (IE) and self- and parent-report measures pre- and post-treatment. Multiple regression mediation analyses examined the degree to which mid-treatment IU mediates the relationship between anxiety severity pre- to post-treatment while controlling for pre-treatment IU. Multiple regression mediation analyses also examined the degree to which post-treatment IU mediates the relationship between anxiety severity pre- to post-treatment while controlling for pre-treatment IU. For both analyses, three separate models were estimated to measure anxiety severity (a) by IE-report, (b) by youth self-report and (c) by parent-report. Results: There were no significant indirect effects for IE-, youth-, or parent-report models when mid-treatment IU or post-treatment IU were tested as potential mediators. Discussion: Additional work is needed to explore other potential mediators of CBT outcomes as well as the role of IU before attempts are made to target IU directly to improve current interventions. Study limitations and future directions are discussed. / Psychology

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Despite major advances in the development of evidence-based practices (EBPs) for child anxiety, there remains a critical need to improve upon current treatments. Identifying common, transdiagnostic processes underlying child anxiety disorders offers a promising avenue to refine conceptualizations of the etiology and maintenance of child anxiety disorders, to enhance the efficacy of interventions, and to facilitate the dissemination of EBPs. Distress intolerance (DI), defined as the perceived inability to tolerate negative somatic and emotional states or experiential discomfort (Simons & Gaher, 2005), is a transdiagnostic factor contributing to multiple forms of mental illness. Emerging research suggests that DI may be associated with elevated anxiety in community samples of youth; however, associations between DI and child anxiety have yet to be evaluated in a clinical population. The present multimodal investigation (N = 56) examined patterns and correlates of DI in a treatment-seeking sample of anxious youth (ANX, n = 28) relative to community controls (COM, n = 28). The aims of the study were to examine differences in DI between ANX and COM youth on self-report and behavioral measures of DI, and to determine the extent to which DI mediates links between child anxiety and associated behavioral avoidance. Youth ages 10-17 completed self-report measures assessing child anxiety symptoms, behavioral avoidance, and DI. Next, participants completed a behavioral task intended to provoke mild levels of distress that assessed behavioral persistence in the face of that distress. Consistent with hypotheses, ANX participants demonstrated higher levels of self-reported DI than COM participants, and greater anxiety-disorder severity was associated with higher levels of self-reported DI. Contrary to hypotheses, there were no between-group differences in behaviorally assessed DI. Mediation analyses revealed that a composite summary score of three self-report DI measures significantly mediated the link between anxiety status and behavioral avoidance. These findings provide compelling preliminary support that self-perceived DI may underlie the behavioral avoidance that is a cardinal feature across anxiety disorders. Results can inform the optimization of EBPs for child anxiety such that clinicians might directly target DI within treatment to better alleviate symptoms and yield more enduring treatment gains in anxiety-disordered youth.

Intolerance of uncertainty (IU) is commonly defined as the tendency for one to interpret uncertainty as negative or threatening. Most general or non-specific measures of IU show a strong relationship with worry and generalized anxiety; however, a specialized measure of intolerance of uncertainty in social situations could provide insight into the role of IU in social anxiety. This study's purpose was to develop and validate the Intolerance of Uncertainty in Social Interactions Scale, a comprehensive measure designed to assess intolerance of uncertainty in social situations. Participants consisted of a non-referred, adult undergraduate sample (N=456). Based on an exploratory factor analysis, a two-factor solution was retained, with factors labeled 'Social Ambiguity' and 'Need to Reduce'. Both subscales were found to have good reliability, construct validity, incremental validity, and internal validity. For example, in terms of incremental validity, the IU-SIS predicted up to 16% of the variance in score on measures of social anxiety after controlling for variance explained by well-established, general measures of IU. The IU-SIS shows great promise as a tool to further investigate the relationship between intolerance of uncertainty and social anxiety.

A study was conducted to test Tomkins' Polarity theory (1963) on the psychological basis for being ideologically liberal or conservative and its relationship with intolerance of ambiguity and gender differences. Normativism, the conservative orientation, was found to have a positive relationship with intolerance for ambiguity. Males were found to be generally less humanist than females. Theoretical background and relevant research is discussed. Suggested applications of this study are to political persuasion, voting behavior, and the psychology of partisanship. This study intends to contribute to the literature on the psychology of ideology, political behavior and ideological differences between men and women.

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