Browsing by Author "MacMaster, Frank"
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- ItemEmbargoAddition of Repetitive Transcranial Magnetic Stimulation to Intensive Interdisciplinary Pain Treatment for Youth with Chronic Pain(2024-02-09) Epp, Spencer Daniel; Miller, Jillian Vinall; Rasic, Nivez; MacMaster, Frank; Birnie, KathrynBackground: Pediatric chronic pain is highly prevalent. The current gold standard of treatment are Intensive Interdisciplinary Pain Treatment (IIPT) programs, providing a multimodal range of therapies over a short time frame. Repetitive transcranial magnetic stimulation (rTMS) of the middle frontal gyrus (MFG) has been shown to be a safe and effective treatment for adults with chronic pain but has not yet been used in youth chronic pain populations. Justifying the use of rTMS to the MFG and determining the safety and tolerance of this application in a pediatric population is critical to advancing pediatric chronic pain management. Methods: 20 youth with chronic pain aged 12-18 years underwent fMRI task-based neuroimaging and completed pain questionnaires before and after IIPT at the Alberta Children’s Hospital. These patients were assessed for changes in brain response to emotional stimuli following treatment in absence of rTMS, and these brain changes were compared to changes to pain interference. 15 further patients completed the IIPT program with the inclusion of rTMS as an additional therapy and were assessed for their tolerance of rTMS and attitude towards the treatment. Results: The non-rTMS group demonstrated a significant positive correlation between a reduction in pain interference and a decrease in MFG activity over the course of treatment. The rTMS group reported similar reductions in pain interference and no major adverse events. Although uncommon, headache, light-headedness, and neck pain were the most frequently reported adverse symptoms. Neck pain was the only symptom found to be consistently exacerbated by rTMS. Pre-IIPT, participants generally expected rTMS to provide great benefit, but post-IIPT reported physio- and psychotherapies as most helpful to their recovery. Conclusions: The fMRI results from the non-rTMS group help justify the use of rTMS in the IIPT. rTMS does not appear to influence established outcomes of the IIPT positively or negatively at this time, though greater sample sizes are needed for more powerful analyses. Action should be taken to minimize minor adverse symptoms during stimulation, however, rTMS is shown to be broadly safe and tolerable for this youth chronic pain population. Future analyses should focus on the magnitude and longevity of influence of rTMS on IIPT outcomes.
- ItemOpen AccessAerobic Exercise and Hippocampal Plasticity in Young Adults with Depression(2014-06-26) Courtright, Allegra; MacMaster, Frank; Culos-Reed, S. NicoleMajor depressive disorder (MDD) is a significant public health problem. Exercise has shown promise in reducing symptoms and promoting brain plasticity in MDD. A relationship between symptom severity, hippocampus volume and N-acetyl-aspartate (NAA) concentration, a marker of neuron density/viability, has been shown. The relationship of these variables to fitness (as assessed by volume of oxygen uptake - VO2 max) is underexplored. In this study, unmedicated, inactive young adults with MDD and healthy controls underwent neuroimaging, fitness and clinical assessments at baseline and after 12-weeks. After 12-weeks of aerobic exercise, VO2max increased and depression scores decreased relative to baseline in participants with MDD. No changes in hippocampal volume or NAA levels were observed, compared to controls. This finding may have resulted from small samples and high variability on the measures of interest. Depression symptom decreases were not related with VO2max changes or exercise compliance.
- ItemOpen AccessBrain Structure and Mental Health Symptoms in Children and Adolescents with Prenatal Alcohol Exposure(2023-06-12) Nakhid, Daphne Kristen Mitchell; Lebel, Catherine; McMorris, Carly; Gibbard, Ben; MacMaster, FrankPrenatal alcohol exposure (PAE) can impact brain development, leading to an increased risk of cognitive difficulties and mental health challenges. Mental health challenges affect many people with PAE, however, associations with brain structure remain unknown. In unexposed populations, mental health symptoms are closely linked to brain volume of subcortical structures and limbic subregions. Whether there is a similar association in individuals with PAE is unknown. Beyond brain volume, iron is a key component of healthy brain development; PAE lowers fetal brain iron and may be associated with the development of mental health symptoms. Whether increased mental health symptoms in youth with PAE are associated with alterations in brain volume or brain iron of subcortical brain structures is yet to be determined. This dissertation used quantitative susceptibility mapping (QSM) and T1-weighted magnetic resonance imaging (MRI) to assess differences in brain iron and brain volume of limbic and subcortical brain regions in youth with and without PAE. Additionally, associations between brain structure and mental health symptoms were assessed within and between groups. Multiple subcortical brain structures and limbic subregions were smaller in the PAE group, but only limbic subregion volume showed associations with mental health symptoms. I found minimal group differences in magnetic susceptibility, a marker of brain iron, but many associations between brain iron and mental health symptoms within and between groups. Furthermore, PAE moderated the association between internalizing symptoms for both brain iron and subnuclei volumes in the thalamus, suggesting that the thalamus may be a unique correlate of mental health symptoms in youth with PAE. This research provides greater insight into limbic subregions that may be affected by PAE that are not observed when looking at the whole volume of a brain region. As the first study to examine magnetic susceptibility in humans with PAE, it provides important information to help understand mental health symptoms in exposed and unexposed populations. This study highlights brain structures and regions that are uniquely associated with mental health symptoms in youth with PAE. Implications of this work include increasing awareness around mental health and promoting appropriate interventions to support youth with PAE.
- ItemOpen AccessDeveloping a provincial patient support network for children and families affected by Tourette syndrome and/or obsessive–compulsive disorder: results of a stakeholder consultation(2021-06-16) Fletcher, Julian; Dimitropoulos, Gina; Martino, Davide; Wilcox, Gabrielle; MacMaster, Frank; Arnold, Paul; Pringsheim, TamaraAbstract Background Tourette syndrome and OCD are disorders that frequently occur in children and cause a high level of disability. In Alberta there is a huge delivery gap in providing healthcare services for children with TS and OCD. A stakeholder consultation was performed to ascertain how service delivery could be improved across the province and to inform the development of a provincial information and support organization, the Tourette OCD Alberta Network. Methods A mixed-methods study was employed: 10 parents were recruited for interview and 140 parents responded to a survey. Results Qualitative data showed there was often an absence of a clear pathway to access healthcare for people with TS and OCD. The negative impact of not receiving treatment, information, and resources in a timely and prompt manner was also revealed. Good clinical practice existed across the province but too often it was hindered by a shortage of knowledge about TS and OCD. In schools, learning for students with TS and OCD was also impaired by educators’ lack of knowledge and preparedness in relation to the disorders. Conclusions This study identified ways that challenges with healthcare access, school learning, and seeking information can be overcome. Skills-based training webinars, educational outreach in schools, and peer support were recognized as actions for improving healthcare outcomes for people with TS and OCD. The aim of the Tourette OCD Alberta Network is to provide services and support that directly address the healthcare service delivery shortfalls shown in this study.
- ItemOpen AccessDevelopment of topographical orientation skills in seven to ten year old children(2017) Liu, Irene; Iaria, Giuseppe; Graham, Susan; MacMaster, Frank; Drefs, Michelle; Uttal, David; Iaria, GiuseppeIn this dissertation, I investigated children’s development of topographical orientation skills. Specifically, I examined children’s performance on a navigation task in a virtual museum. In Chapter 2, I described the methodology used in this experiment. The computer task comprised of an interactive game that consisted of three sections: a practice motor task, a guided tour around a virtual museum, and a testing phase. After children were introduced to the environment, they were required to navigate from one location of the museum to a goal location as quickly as possible. Game performance was assessed by how much time and travel distance were required to reach a target location. In order to assess different cognitive domains supporting topographical orientation skills, a neuropsychological battery was administered. Finally, both children and parents completed self-rated questionnaires of the children’s general spatial behaviours. In Chapter 3, the main experimental results were described. Game performance was significantly correlated with age and several neuropsychological measures with emphasis on visual spatial processing. Game performance was also correlated with history of gaming experience and technology use. A multiple linear regression analysis revealed that game performance was best explained by performance on spatial working memory and visual-spatial organization tasks, once video game experience was accounted for. Only children’s self-reported ratings of their spatial orientation and navigation skills were correlated with one of two measures of game performance, whereas parents’ ratings were not. When compared to adult performance on the computer game, even the oldest group of children tested was still not as efficient as adults in solving the task, suggesting that development of topographical orientation skills continue well into adolescence and young adulthood. Chapter 4 summarized and explored the aforementioned findings in greater detail. Additional statistical analyses and discussion regarding the pilot study, a group of children who participated in a repeat session of the computer game, and a group of younger children tested are described in Appendix B.
- ItemOpen AccessEffects of Repetitive Transcranial Magnetic Stimulation and Possible Predictors of Response in Youth with Treatment Resistant Depression(2016) Jasaui, Yamile; MacMaster, Frank; Hill, Matthew; Patten, ScottAdolescents with treatment-resistant depression (TRD) do not respond to conventional antidepressant interventions. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapeutic technique to treat TRD. The left dorsolateral prefrontal cortex (DLPFC), important in emotion regulation and the excitatory neurotransmitter glutamate, are altered in TRD. rTMS applied to the left DLPFC can increase glutamate concentrations in this area. Adolescents (aged 12-21) underwent 3 weeks of rTMS, pre and post magnetic resonance spectroscopy (MRS) to measure glutamate concentrations and weekly Ham-D depression rating scale applications. A 50% reduction in depression scores indicated response to treatment. Depression scores decreased in all participants but declined significantly in responders whose glutamate concentrations pre-treatment were considerably lower. Thus, low glutamate concentrations pre-treatment might be a biomarker of response to rTMS. One explanation for this result is that rTMS stimulates glutamate release, which activates the left DLPFC’s emotional regulation function, which in turn reduces depressive symptomatology.
- ItemOpen AccessEfficacy of Connectivity-Based Targeting in TMS for Adolescents with Treatment-Resistant Depression(2021-04-29) Tapia Palacio, Clara; MacMaster, Frank; Bray, Signe; Rittenbach, Katherine; Kopala-Sibley, DanielBackground. Thirteen percent of 12- to 17-year-old adolescents suffer from depression, but only half respond to antidepressants and psychotherapy. Recent studies have successfully employed repetitive Transcranial Magnetic Stimulation (rTMS) to treat depression. However, there is a need to precisely determine the rTMS site of stimulation. A recent study in adults with depression (Fox et al., 2012) proposes that using the connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate to define the site of stimulation for rTMS results in increased clinical efficacy. To date, no studies have investigated this phenomenon in the pediatric population. Methodology. Functional magnetic resonance imaging (fMRI) scans of 37 adolescents with treatment-resistant depression (TRD) and 18 controls were analysed. TRD individuals underwent 15 consecutive rTMS sessions and were assessed for depression before and after treatment by the Hamilton Depression Rating Scale (Ham-D). We calculated the DLPFC-Subgenual connectivity for the seven different rTMS targeting approaches described in Fox et al. (2012). Then, we measured the DLPFC-Subgenual connectivity from the individual stimulation sites and explored any correlation with clinical efficacy. Results. Contrary to Fox et al. (2012), four and three targeting approaches presented a positive correlation for the TRD and control groups respectively. Moreover, more positive values of DLPFC-Subgenual connectivity were significantly associated with a higher decrease in Ham-D scores (p = 0.025, one-tailed). Limitations. We used coordinates for the targeting approaches and subgenual cingulate that had been originally defined in adults. Furthermore, small changes in the noise reduction procedure causes great divergence in the outcomes. Conclusions. Since adolescents showed a distinctive and stronger functional connectivity between DLPFC and the subgenual cingulate, depression treatments have to be directly adjusted to pediatric population. Additionally, higher DLPFC-Subgenual positive connectivity predicted a higher clinical efficacy. This suggests that future work should consider defining the stimulation site at the DLPFC location with the strongest positive connectivity with the subgenual cingulate. However, the novelty of this research and the differences in outcomes with the literature in adult population indicates that reanalysing this association is necessary.
- ItemOpen AccessExamining Associations Between Severity of Parental Depression and Anxiety Symptoms and Offspring Grey Matter(2022-07-18) Kemp, Jennifer Victoria Anne; Kopala-Sibley, Daniel; Pittman, Quentin; MacMaster, FrankThe aim of this thesis was to explore associations between severity of parental depression and anxiety symptoms, and offspring brain structure. Additionally, to see whether certain brain regions in offspring were uniquely associated to parental depression versus anxiety. One hundred and twenty-four adolescents aged 11-18 years (M= 13.64, SD= 1.51) were included in the final analysis. Each adolescent had to have at least one parent with a diagnosed mood disorder as per the Mini International Neuropsychiatric Interview (MINI). Adolescents themselves were to be free of any psychopathology at baseline as per the MINI-Kid. Parents filled out the Beck Depression Inventory (BDI-II) and the Generalized Anxiety Disorder Assessment (GAD-7) to assess current symptom severity and youths underwent magnetic resonance imaging on a 3 Tesla magnet to obtain brain structure data. Bivariate correlations revealed that higher parental depression scores were associated with greater cortical thickness in the left middle temporal gyrus, and that higher parental anxiety scores were associated with greater cortical thickness in the right middle temporal gyrus. After controlling for offspring age and intracranial volume (ICV), the left middle temporal gyrus remained significantly associated with parental depression and the right middle temporal gyrus was no longer significantly associated with parental anxiety. Higher parental anxiety scores were significantly associated with cortical thinning in the left inferior parietal region when controlling for offspring age and ICV. Greater cortical thickness in the left middle temporal gyrus was uniquely associated with higher parental depression scores, and reduced cortical thickness in the left inferior parietal region was uniquely associated with higher parental anxiety scores. These findings suggest that even within a group of high-risk adolescents, there may be elevated risk for altered grey matter volume and thickness depending on parent symptom severity.
- ItemOpen AccessExploring the experience of boarded psychiatric patients in adult emergency departments(2021-09-27) Major, Daniel; Rittenbach, Katherine; MacMaster, Frank; Walia, Hina; VandenBerg, Stephanie D.Abstract Background This study quantifies the frequency of adverse events (AEs) experienced by psychiatric patients while boarded in the emergency department (ED) and describes those events over a broad range of categories. Methods A retrospective chart review (RCR) of adult psychiatric patients aged 18–55 presenting to one of four Calgary EDs (Foothills Medical Centre (FMC), the Peter Lougheed Centre (PLC), the Rockyview General Hospital (RGH), and South Health Campus (SHC)) who were subsequently admitted to an inpatient psychiatric unit between January 1, 2019 and May 15, 2019 were eligible for review. A test of association was used to determine the odds of an independent variable being associated with an adverse event. Results During the study time period, 1862 adult patients were admitted from EDs (city wide) to the psychiatry service. Of the 200 charts reviewed, the average boarding time was 23.5 h with an average total ED length of stay of 31 h for all presentations within the sample. Those who experienced an AE while boarded in the ED had a significantly prolonged average boarding time (35 h) compared to those who did not experience one (6.5 h) (p = 0.005). Conclusions The length of time a patient is in the emergency department and the length of time a patient is boarded after admission significantly increases the odds that the patient will experience an AE while in the ED. Other significant factors associated with AEs include the type of admission and the hospital the patient was admitted from.
- ItemOpen AccessMeasurement of the Cerebellar Vermis in Bipolar Disorder and the Effect of Lithium Treatment(2014-05-01) Mahnke, Devin; MacMaster, Frank; MacQueen, GlendaPrevious studies have suggested that the cerebellar vermis may be smaller in individuals with bipolar disorder, but these findings are inconsistent and have not considered the potential impact of medication. To address these knowledge gaps, the cerebellar vermis was measured using structural magnetic resonance imaging in both an adolescent and an adult sample. Analysis of variance was performed on the cross-sectional area of the three vermal lobes and on the total area. There were no significant differences between adolescent or adult bipolar subjects compared to healthy controls in any region, regardless of lithium treatment. In addition, a medication-naïve subset of the adult population underwent a two-year course of lithium treatment and was then reassessed. No changes in vermis area were found within subjects across the treatment. These results, combined with literature meta-analysis, indicate no clear effect of either bipolar disorder, or lithium treatment, on the size of the cerebellar vermis.
- ItemOpen AccessOutdoor Air Pollution in Canada: Associations with Major Depressive Episodes and Depressive Symptoms(2021-07-08) Dores, Ashley Katherine; Patten, Scott; Fick, Gordon; MacMaster, FrankObjective: The objective of this thesis was to assess whether exposure to increased levels of outdoor air pollution is associated with an increased prevalence of major depression. Methods: The prevalence of major depressive episode (MDE) from 2011 to 2014 and moderate-severe depressive symptoms of major depression from 2015-2016 were derived from six consecutive survey years of the annual Canadian Community Health Survey (CCHS). The Canadian Urban Environmental Research Consortium provided estimates of the annual average concentration of fine particulate matter ≤2.5 micrometers (µm) in diameter (PM2.5) (2012-2015), ozone (O3) (2013-2015), sulfur dioxide (SO2) (2011-2015), and nitrogen dioxide (NO2) (2012). Outdoor air pollution data was linked with the annual CCHS survey data via 6-digit residential postal codes. Long-term exposure to increased levels of residential outdoor air pollution was defined by the upper quartile of the annual average concentration of PM2.5, O3, SO2, and NO2. Log-binomial models were used to estimate prevalence ratios with corresponding 95% confidence intervals. Single outdoor air pollutant models included adjustment for age, sex, marital status, income, education, employment status, urban versus rural households, cigarette smoking, and chronic illness. Results: Overall, these findings did not suggest that exposure to increased levels of outdoor air pollution is associated with an elevated prevalence of MDE or moderate-severe symptoms of major depression. No evidence of modification or confounding was observed. Conclusions: The analysis did not find evidence that outdoor air pollution is associated with major depression in Canada. Although outdoor air pollution was not identified as a neighbourhood-level determinant of major depression, these results should be generalized to other countries with caution. The null results that we observed may be due to the relatively low levels of outdoor air pollution in Canada. Air pollution at these levels may not be sufficient to activate the relevant mechanisms of major depression (e.g., inflammation, aggravation of chronic conditions, production of depressive symptoms). Future research should examine whether outdoor air pollution is linked to major depression in regions with higher levels of outdoor air pollution or during intervals of elevated exposure such as those that may occur during natural disasters.
- ItemOpen AccessThe Effects of Prenatal Cortisol Concentrations on Working Memory Performance in Preschool Children(2016) Cameron, Emily; Tomfohr-Madsen, Lianne; Giesbrecht, Gerald; Goghari, Vina; Campbell, Tavis; MacMaster, FrankWorking memory has been shown to predict future cognitive and academic outcomes, making the successful development of working memory crucial. Extensive animal literature has reported a relationship between elevated maternal cortisol in utero and poorer working memory performance in offspring, while this association has not been replicated in humans. The current study aims to investigate the effect of maternal cortisol exposure on working memory development in preschool aged children. Maternal salivary cortisol was collected over two consecutive days at three prenatal assessments. Child working memory was assessed at age 3-4 years. Results indicated that there was no association between a working memory composite score and maternal cortisol; however, the current study was underpowered. Individual subtest analyses revealed significant three-way interactions for two subtests with infant biological sex and gestational age. Future research should investigate the relationship between prenatal cortisol and working memory under varying conditions of stress in children.
- ItemOpen AccessThe Progression of Serious Mental Disorders to Mortality in Primary Care(2016) Vallerand, Isabelle; Patten, Scott; Bulloch, Andrew; Duffy, Anne; Addington, Donald; MacMaster, Frank; Lesage, AlainSerious mental disorders (schizophrenia, bipolar disorder and major depressive disorder (MDD)) have been associated with an excess risk of mortality. However, most datasets used to study these associations have been limited by small sample sizes, use of specialized clinical samples, and few covariates recorded, thereby impeding proper assessments of mortality risks. Electronic medical records databases such as The Health Improvement Network (THIN) directly address these limitations by offering a large primary care population for study, with inclusion of numerous clinically-relevant covariate data over a long follow-up period. To date, THIN has not been used to study mortality in serious mental illness. As such, this thesis had the following objectives: i) estimate annual prevalence of serious mental illness; ii) determine the covariate-adjusted and unadjusted risk of all-cause mortality in serious mental illness and iii) demonstrate the feasibility of using THIN to study the excess mortality associated with serious mental illness. THIN was used to define schizophrenia, bipolar disorder and MDD cohorts between the years of 1986-2012, where annual prevalence estimates in 2012 were 0.23%, 0.26% and 9.49% respectively. Survival analyses adjusted for important covariates revealed that in the schizophrenia cohort (n=6,056), the risk of all-cause mortality was more than double (HR=2.36, 95%CI: 1.83 – 3.04) the risk in the referent cohort (n=6,137,760). Similarly, patients with bipolar disorder (n=9,425) were found to have twice the risk of all-cause mortality (HR=2.00, 95%CI: 1.70-2.34) compared to the referent cohort (n=6,131,373). Patients with MDD (n=405,866) were also found to have a significantly greater risk of all-cause mortality (HR=1.28, 95%CI: 1.21-1.36) compared to the referent cohort (n=5,337,098). Annual prevalence estimates for schizophrenia and MDD were similar to previous reports, but estimates were lower for bipolar disorder, possibly due to issues in correctly identifying these patients in primary care. This study was the first to confirm the excess mortality associated with serious mental disorders using THIN, highlighting that studying mortality among patients with serious mental illness is feasible in THIN. As such, the work presented in this thesis can pave the way for future research using THIN to improve the health of patients with serious mental disorders.