The 5-HT agonist drug mCPP contributed to a 5-HT hypothesis of obsessive-compulsive disorder (OCD), but the effects of the drug in human and animal studies have been inconsistent. The objective of this thesis was to shed light on the behavioural and neurobiological effects of mCPP using the quinpirole sensitization rat model of OCD and in a reciprocal manner, to use the drug to further reveal behavioural and neurobiological components of the animal model. The utility in using the quinpirole model is that the process of analysis by experimentation can be employed to observe effects of the drug on three separate behavioural components identified to underlie the model compulsive behaviour: vigor, focus and satiety. Four original studies were designed to address this objective, and the findings yielded novel contributions to the literature. We suggest that mCPP attenuates compulsive checking by attenuating the exacerbated vigor and satiety characteristic of compulsive behavior, but this effect may not have been captured in previous clinical studies because OCD was measured as a unitary phenomenon across different symptom subtypes. We also reveal that separate systems underlie the development and performance of compulsive behaviour in the animal model, and mCPP reduces its performance but not its development. Hence, the animal model findings suggest that mCPP can attenuate performance of OCD behavior but the drug does not reverse the pathology of OCD or arrest the pathogenesis of OCD. Neurobiologically, we hypothesize that the underlying mechanism mediating the response to mCPP is mediated downstream of the nucleus accumbens core (NAc), at the substantia nigra pars reticulata, based on the finding that the effects of mCPP on vigor and satiety are present in NAc lesioned animals. Finally, although findings of this thesis indicate that 5-HT2A/C receptors do not mediate the response to mCPP, an oppositional role for DA and 5-HT on the model of compulsive behaviour is proposed, consistent with a security motivation theory of OCD. Overall, this thesis shed new light on the effects of mCPP on OCD, and reveals novel neurobiological and behavioural correlates of the quinpirole model. / Thesis / Doctor of Philosophy (PhD)

No description available.

This study aimed to characterize and assess the subjective impact of the COVID- 19 pandemic on symptom severity and psychosocial experiences of youth with chronic tic disorders (CTD), obsessive-compulsive disorder (OCD), and co-occurring tic and OCD (Tics+OCD) through the use of Likert scales and validated measures. Children and adolescents aged 6 to 18 and their parents were asked to complete an online survey from July 2020 to April 2021. Overall, youth in the study reported negative pandemic-related impact on several domains, particularly after-school activities, relationships with friends, and family and community gatherings. Though limited by the small sample size of the group, youth with OCD appeared to report more negative impact compared to the other diagnostic subgroups. The median screen use for youth in this study was 3-8 hours a day; youth who reported >8 hours of screen time per day on weekends trended towards a 13x greater odds of depression compared to those with <8 hours per day although not statistically significant. If future public health emergencies were to ensue, supports aimed at helping these particularly vulnerable youth navigate the impact of those restrictions would be welcome and important to their mental health and general well-being.

The primary purpose of this study was to examine the role of motivation in the treatment of individuals hospitalized for severe OCD, specifically, the extent to which an individual’s motivation for treatment and motivational orientation (intrinsic or extrinsic motivation) predict OCD treatment response. The sample consisted of 142 individuals diagnosed with severe treatment-refractory OCD participating in an intensive treatment program. Patients completed a measure assessing overall motivation and motivational orientation at admission (TSRQ), and measures assessing depressive severity (BDI) and OCD symptom severity (Y-BOCS) at admission and discharge. Hierarchical multiple regression analyses were performed in which admission levels of overall motivation, intrinsic motivation, and extrinsic motivation were examined as predictors of OCD treatment response when controlling for length of treatment and baseline levels of OCD and depressive symptoms. Results indicate that a high initial level of extrinsic motivation was associated with poorer treatment outcome when controlling for other variables. Furthermore, findings suggest intrinsic motivation appears to have an interactive effect with OCD symptom severity, such that a high level of intrinsic motivation at the outset of treatment may predict positive treatment outcome when OCD symptoms are more severe. Overall initial level of motivation was not found to be a significant predictor of OCD treatment outcome. Treatment implications and suggestions for future research are discussed.

Historically, racial and ethnic minority (REM) communities have faced reduced access to resources for mental and emotional health issues. While research has placed a greater emphasis on REM experiences, there is still a need to further understand the unique contextual factors surrounding mental health challenges among these marginalized groups. Research on Obsessive Compulsive Disorder (OCD) among REM communities is one area in need of further evaluation. Therefore, this study is a content analysis of literature analyzing the current research focused on the intersection of REM communities and OCD experiences. The purpose of the study is to analyze OCD research among REM communities in the United States in order to support researchers and clinicians with the tools and direction needed to provide greater representation, more effective treatment, and higher quality of life for these underserved populations. Across a 21 year-span analyzed (2000-20), 47 articles were found with a focus on OCD among REM populations, with African Americans having the largest proportion of focus (27 articles, 57.4%). 8 of the 47 articles (22%) utilized ethnic identity measures, and none of the articles assessed acculturation. 11 of the articles included clinical samples, and 28 of 47 (60%) articles were funded. Utilization of OCD measures, common research topics, and implications for clinical work and future research are also examined and discussed.

Context maintenance, an aspect of cognitive control, is the internal representation and utilization of task-relevant information that helps achieve task goals. Alterations in context maintenance may be responsible for the cognitive difficulties seen in people with obsessive-compulsive disorder (OCD). We used two tasks designed to measure context maintenance: a) the cued-Stroop, a single-trial version of Golden’s Stroop test that varies the cue for each trial (color-naming or word-reading), and b) the AX-CPT task, a continuous performance task that has participants respond to an “A” only when followed by an “X,” with all other non-target trials labeled as AY, BX, and BY (and “Y” and “B” representing all non-X and non-A letters, respectively). Participants included 31 people with OCD and 30 psychiatrically-healthy controls that completed a neuropsychological test battery, self-report questionnaires measuring mood and symptom severity, and the computerized cued-Stroop and AX-CPT tasks. There was a 1s or 5s delay between the cue and probe for both tasks so as to vary the duration of context maintenance. We conducted a 2 (Group) x 2 (Delay) x 3 (Trial Type) repeated measures ANOVA for the cued-Stroop and a 2 (Group) x 2 (Delay) x 4 (Trial Type) repeated measures ANOVA for the AX-CPT. Dependent measures included median reaction times (RT) and mean error rates (ER). Both groups showed a congruency effect for the cued-Stroop, with slower RTs and greater ERs for the incongruent trials than the neutral and congruent trials, as well as lower ERs for BY trials compared to BX and AY trials of the AX-CPT task. There were no significant differences in RTs or ERs between groups for delay or condition for the cued-Stroop (ps > .45) or for the AX-CPT (ps > .07). The present study shows that people with OCD did not show deficits in context maintenance in two separate tasks. Limitations include low power, higher functioning participants with OCD, and the presence of comorbid depression and anxiety in some participants with OCD.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is considered the “gold standard” for measuring symptoms for Obsessive-Compulsive Disorder (OCD) due to the high reliability and validity of the measure. Originally, the Y-BOCS was divided into Obsessive and Compulsive factors; however, literature on the factor structure of the Y-BOCS is inconsistent. Models range from one global factor to different interpretations of bi-factor models to three-factor models. Inconsistencies between models may be attributed to sampling error, including participants with subclinical OCD in some samples, and measurement error. In addition, many researchers treat the Y-BOCS measurement as an interval or ratio scale when it likely reflects ordinal measurement. Our paper has two primary aims. First, we compare the fit of the models proposed in the literature using a large sample from multiple sites of patients diagnosed with OCD. We also evaluate how the models can be improved and whether those improvements show evidence for convergent validity. We treat the Y-BOCS observations as ordinal data. Second, we evaluate measurement and structural invariance between genders. Additionally, we examine convergent validity of the factor structure of the best fitting model with subscales of the OCI-R. Data from five separate samples were combined into one dataset with 288 total participants all formally diagnosed with OCD. We selected several Y-BOCS factor models from the literature and used confirmatory factor analysis to evaluate goodness of fit indices on our pooled sample. Only one model approached acceptable goodness of fit indices. We considered the factors in this model and proposed a new factor model with a global factor (OCD) and two sub-factors (Obsessions and Resistance to Symptoms). Our model exhibited the highest goodness of fit indices which we further improved with modifications to our factor model. On invariance analyses, our model exhibited measurement invariance between genders and partial structural invariance. Additionally, the latent factors of our model exhibited convergent validity with all of the OCI-R subscales (except Ordering). Our model exhibited stronger goodness of fit indices with our data than existing models in the Y-BOCS literature and measurement invariance and partial structural invariance between genders. We recommend that future studies replicate the efficacy of our factor model using the Y-BOCS as an ordinal measurement.

No description available.

<p>The human brain is possibly the most complicated structure in the known world. It contains 100 billion neurons, each making contact with 1,000 to 10,000 other neurons. The neurons themselves have hundreds of excitatory and inhibitory neurotransmitters / receptors with which to use to activate or de-activate other neighbouring neurons. Ultimately these neurons are organized into locally defined functional neural networks, which in turn connect with other neural networks to create non-localized highly-complex brain circuits. These brain circuits are responsible for the higher order functions such as perception, emotions, learning, language and conscious thought. In healthy brain states, these networks and circuits are communicating and signalling appropriately. With mental illness, or in an intoxicated brain state, however, this network and circuit functioning can become disrupted: either in a very specific manner, or in a generalized form. Alcohol (in the form of ethanol) is one of the oldest and most widely used psychoactive drugs in the world. In recreational doses, it can have drastic effects on how a person thinks and behaves. Small doses will lead to feelings of euphoria, increased sociability, and impaired judgement, while larger doses will lead to impaired memory and comprehension, and at extreme doses will lead from confusion and stupor to coma and death. The current understanding of alcohol’s effects on the brain is that it acts in a very specific way on a variety of brain enzymes and receptors. This in turn affects specific brain circuitries, making alcohol intoxication a promising model of pharmacological neural network and brain circuit modulation. Obsessive-compulsive disorder (OCD) is a major psychiatric disorder that affects many (lifetime prevalence of between 1-2.5%) and can cause significant disability and impairment in one’s life. The onset of OCD is usually during childhood and adolescence, with more than 50% of adults with OCD reporting its onset occurring before the age of 18. The etiological origin of OCD lies ultimately in specific neuropathological processes, with current theories postulating either a neurochemical model that emphasizes the dysfunction of the serotonergic and possibly dopaminergic systems; or a neuroanatomical model that emphasizes the dysfunction of a specific corticostriatal pathway; or both. Magnetic resonance imaging (MRI), with its safe, non-invasive ability to image both anatomy, brain function and brain metabolism, provides a unique tool with which to probe brain circuit changes, such as in healthy subjects under a pharmacological challenge (ethyl alcohol), or in medication naïve children with OCD. In the ethanol intoxicated brain, functional MRI can be used to probe specific resting state networks (RSN; functionally connected networks that exhibit low frequency blood oxygen level dependent (BOLD) fluctuations), measure brain BOLD time-signal complexity using fractal analysis, and to correlate these findings with measured alcohol levels in the brain in vivo using magnetic resonance spectroscopy (MRS). In subjects with OCD, functional MRI can be used to once again probe RSNs, and as well, MRS can be used to look at potential differences in brain metabolites in axonal projections that connect OCD relevant brain circuits. It is the purpose of this thesis to show how brain circuits and neural networks in atypical brain states (such as intoxication or mental illness) can be probed and better understood using advanced MRI techniques, such as resting state fMRI. Over a series of three studies, one involving MRI scans of healthy male adults before and after drinking a substantial amount of ethanol, and two others comparing RSNs in children with OCD versus healthy matched controls, and MRS differences in prefrontal white matter between the same two groups, we examined brain circuit changes using advanced MRI techniques. In the alcohol study, evidence was found of brain signal complexity decreasing after 60min and 90min post alcohol consumption. Simultaneously, a mixture of increased and decreased functional connectivity in the default mode network was found after 60min post alcohol consumption, which became general decreased functional connectivity after 90min post alcohol consumption. These changes took place while alcohol in the brain increased substantially after 60min. These findings may help provide insight into the neurofunctional underpinnings of the cognitive and behavioural changes observed during acute alcohol intoxication. In the first study on medication naïve children with OCD, we observed increased connectivity (OCD>control) in the right section of Brodmann area 43 of the auditory cortex, as well as decreased connectivity in the right section of Brodmann area 8 and Brodmann area 40 in the cingulate network. In the second study looking at medication naïve children with OCD, we observed higher levels of N-acetyl-aspartate (NAA) and choline in the right prefrontal white matter (RPFWM) in children with OCD compared to healthy controls, as well as a positive correlation of creatine, NAA, and myo-inositol levels in the RPFWM and OCD symptom severity. Both studies lend further support to the cortico-striatal-thalamiccortical hypothesis of OCD, while the first study further implicates other regions of the brain outside of the CSTC. Both of these OCD studies further demonstrated the differences in brain circuits of neuropsychiatric disorders between children and adults.</p> / Doctor of Philosophy (PhD)

Given the high rates of treatment drop-out and non-compliance within empirically-based treatments for OCD, it is important to increase our understanding of factors that impact the treatment process. Two studies were conducted to evaluate the clinical utility of the Obsessive Compulsive Consequences Scale-Revised (OCCS-R) and increase understanding of the relationships between the prognostic factors of motivation, insight, treatment compliance and treatment outcome. Study 1 used maximum likelihood Confirmatory Factor Analysis to show the OCCS-R's four factor solution was an adequate fit in a sub-clinical college population. Study 2 evaluated the clinical utility of the OCCS-R for predicting treatment outcome and its relationship to identified predictor variables. The OCCS-R predicted treatment drop-out but did not predict symptom improvement. Some support was found for predicted relationships between the OCCS-R and its factors, a general measure of motivation and treatment compliance. No variables predicted symptom improvement. Insight and initial symptom severity predicted treatment motivation which in turn predicted treatment compliance. / Ph. D.