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Environmental and genetic factors contribute to schizophrenia etiology, yet few studies have demonstrated how environmental stimuli impact genes associated with the disorder. Immediate early genes (IEGs) are of great interest to schizophrenia research because they are activated in response to physiological stress from the environment, and subsequently regulate the expression

Environmental and genetic factors contribute to schizophrenia etiology, yet few studies have demonstrated how environmental stimuli impact genes associated with the disorder. Immediate early genes (IEGs) are of great interest to schizophrenia research because they are activated in response to physiological stress from the environment, and subsequently regulate the expression of downstream genes that are essential to neuropsychiatric function. An IEG, early growth response 3 (EGR3) has been identified as a main gene involved in a network of transcription factors implicated in schizophrenia susceptibility. The serotonin 2A receptor (5-HT2AR) seems to play an important role in schizophrenia and the dysfunction of the 5-HT2AR encoding gene, HTR2A, within the prefrontal cortex (PFC) contributes to multiple psychiatric illnesses including schizophrenia. EGR3's role as a transcription factor that is activated by environmental stimuli suggests it may regulate Htr2a transcription in response to physiological stress, thus affecting 5-HT2AR function in the prefrontal cortex (PFC). The aim of this study was to examine the relationship between Egr3 activation and Htr2a expression after an environmental stimulus. Sleep deprivation is an acute physiological stressor that activates Egr3. Therefore to examine the relationship between Egr3 and Htr2a expression after an acute stress, wild type and Egr3 knockout mice that express EGFP under the control of the Htr2a promoter were sleep deprived for 8 hours. We used immunohistochemistry to determine the location and density of Htr2a-EGFP expression after sleep deprivation and found that Htr2a-EGFP expression was not affected by sex or subregions of the PFC. Additionally, Htr2a-EGFP expression was not affected by the loss of Egr3 or sleep deprivation within the PFC. The LPFC subregions, layers V and VI showed significantly more Htr2a-EGFP expression than layers I-III in all animals for both sleep deprivation and control conditions. Possible explanations for the lack of significant effects in this study may be the limited sample size or possible biological abnormalities in the Htr2a-EGFP mice. Nonetheless, we did successfully visualize the anatomical distribution of Htr2a in the prefrontal cortex via immunohistochemical staining. This study and future studies will provide insight into how Egr3 activation affects Htr2a expression in the PFC and how physiological stress from the environment can alter candidate schizophrenia gene function.
ContributorsSabatino, Alissa Marie (Author) / Gallitano, Amelia (Thesis director) / Hruschka, Daniel (Thesis director) / Maple, Amanda (Committee member) / Barrett, The Honors College (Contributor)
Created2014-05
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ABSTRACT
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates

ABSTRACT
Environmental and genetic factors influence schizophrenia risk. Individuals who have direct family members with schizophrenia have a much higher incidence. Also, acute stress or life crisis may precede the onset of the disease. This study aims to understand the effects of environment on genes related to schizophrenia risk. It investigates the impact of sleep deprivation as an acute environmental stressor on the expression of Htr2a in mice, a gene that codes for the serotonin 2A receptor (5-HT2AR). HTR2A is associated with schizophrenia risk through genetic association studies and expression is decreased in post-mortem studies of patients with the disease. Furthermore, sleep deprivation as a stressor in human trials has been shown to increase the binding capacity of 5-HT2AR. We hypothesize that sleep deprivation will increase the number of cells expressing Htr2a in the mouse anterior prefrontal cortex when compared to controls. Sleep deprived that mice express EGFP under control of the Htr2a promoter displayed anteroposterior gradients of expression across sagittal sections, with concentrations seen most densely within the prefrontal cortex as well as the anterior pretectal nucleus, thalamic nucleus, as well as the cingulate gyrus. Htr2a-EGFP expression was most densely visualized in cortical layer V and VI pyramidal neurons within the lateral prefrontal cortex of coronal sections. Furthermore, the medial prefrontal cortex contained significantly cells expressing Htr2a¬-EGFP than the lateral prefrontal cortex. Ultimately, the hypothesis was not supported and sleep deprivation did not result in more ¬Htr2a-EGFP expressing cells compared to basal levels. However, expressing cells appeared visibly brighter in sleep-deprived animals when compared to controls, indicating that the amount of intracellular Htr2a-GFP expression may be higher. This study provides strong visual representations of expression gradients following sleep deprivation as an acute stressor and paves the way for future studies regarding 5H-T2AR’s role in schizophrenia.
ContributorsSchmitz, Kirk Andrew (Author) / Gallitano, Amelia (Thesis director) / Stout, Valerie (Committee member) / Maple, Amanda (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels

Egr3 is an immediate early gene transcription factor that shows genetic association with schizophrenia, and is found in decreased levels in the brains of schizophrenia patients. Schizophrenia patients also exhibit cognitive and memory deficits, both of which Egr3 has been shown to play a crucial role in. Additionally, high levels of DNA damage are found in the brains of schizophrenia patients. A recent study has shown that DNA damage occurs as a result of normal physiological activity in neurons and is required for induction of gene expression of a subset of early response genes. Also, failure to repair this damage can lead to gene expression in a constitutive switched on state. Egr3 knockout (Egr3-/-) mice show deficits in hippocampal synaptic plasticity and memory. We were interested in characterizing downstream targets of EGR3 in the hippocampus. To determine these targets, electroconvulsive seizure (ECS) was carried out in Egr3 -/- versus wild type (WT) mice, and a microarray study was first done in our lab. ECS maximally stimulates Egr3 expression and we hypothesized that there would be gene targets that are differentially expressed between Egr3 -/- and WT mice that had been subjected to ECS. Two separate analyses of the microarray yielded 65 common genes that were determined as being differentially expressed between WT and Egr3 -/- mice after ECS. Further Ingenuity Pathway Analysis of these 65 genes indicated the Gadd45 signaling pathway to be the top canonical pathway, with the top four pathways all being associated with DNA damage or DNA repair. A literature survey was conducted for these 65 genes and their associated pathways, and 12 of the 65 genes were found to be involved in DNA damage response and/or DNA repair. Validation of differential expression was then conducted for each of the 12 genes, in both the original male cohort used for microarray studies and an additional female cohort of mice. 7 of these genes validated through quantitative real time PCR (qRT-PCR) in the original male cohort used for the microarray study, and 4 validated in both the original male cohort and an independent female cohort. Bioinformatics analysis yielded predicted EGR3 binding sites in promoters of these 12 genes, validating their role as potential transcription targets of EGR3. These data reveal EGR3 to be a novel regulator of DNA repair. Further studies will be needed to characterize the role of Egr3 in repairing DNA damage.
ContributorsBarkatullah, Arhem Fatima (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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This study examines how a 2013 Arizona law on shared parenting would affect living arrangements, and thus mental health measures. There were two hypotheses. According to the Law Change Hypothesis, it was hypothesized that parenting time in Arizona would be more equal following the 2013 Arizona law change while there

This study examines how a 2013 Arizona law on shared parenting would affect living arrangements, and thus mental health measures. There were two hypotheses. According to the Law Change Hypothesis, it was hypothesized that parenting time in Arizona would be more equal following the 2013 Arizona law change while there would be no change in parenting time in other states following the 2013 Arizona law change. It was further hypothesized that child mental health would be better after the law change in Arizona with no change being seen in other states. Results of this study were almost completely inconsistent with the hypothesis. According to the Law Reflect Hypothesis, the law is actually reflecting the behavior of the community and their thoughts on equal parenting time becoming more favorable, and therefore a change towards more equal parenting time would be found prior to 2013 in Arizona with no change seen in other states. Furthermore, as the Arizona community’s behavior changed, child mental health would be better with no change being seen in other states. Regressions found that a small change toward more equal parenting and closeness with father was prior to 2013 for Arizona students, compared to out-of-state students, although it did not find that the year of divorce resulted in less anxiety, stress, and depression. This partially agrees with past research that the 2013 law is working as intended, even if it started working earlier than we thought. This does not agree with previous research stating there is a connection between equal parenting and better mental health. This is important because this study questions the efficacy of an important and controversial policy. If future studies are consistent with this one, the effectiveness of the Arizona 2013 law change on mental health will need to be further evaluated.

ContributorsTselos, Zoe Rebecca (Author) / Fabricius, William (Thesis director) / Corbin, William (Committee member) / Spinrad, Tracy (Committee member) / Department of Psychology (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / School of Social Transformation (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded

"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded the alarm regarding social media’s unavoidable global impact. He is only one of social media’s countless critics. The more disturbing issue resides in the empirical evidence supporting such notions. At least 95% of adolescents own a smartphone and spend an average time of two to four hours a day on social media. Moreover, 91% of 16-24-year-olds use social media, yet youth rate Instagram, Facebook, and Twitter as the worst social media platforms. However, the social, clinical, and neurodevelopment ramifications of using social media regularly are only beginning to emerge in research. Early research findings show that social media platforms trigger anxiety, depression, low self-esteem, and other negative mental health effects. These negative mental health symptoms are commonly reported by individuals from of 18-25-years old, a unique period of human development known as emerging adulthood. Although emerging adulthood is characterized by identity exploration, unbounded optimism, and freedom from most responsibilities, it also serves as a high-risk period for the onset of most psychological disorders. Despite social media’s adverse impacts, it retains its utility as it facilitates identity exploration and virtual socialization for emerging adults. Investigating the “user-centered” design and neuroscience underlying social media platforms can help reveal, and potentially mitigate, the onset of negative mental health consequences among emerging adults. Effectively deconstructing the Facebook, Twitter, and Instagram (i.e., hereafter referred to as “The Big Three”) will require an extensive analysis into common features across platforms. A few examples of these design features include: like and reaction counters, perpetual news feeds, and omnipresent banners and notifications surrounding the user’s viewport. Such social media features are inherently designed to stimulate specific neurotransmitters and hormones such as dopamine, serotonin, and cortisol. Identifying such predacious social media features that unknowingly manipulate and highjack emerging adults’ brain chemistry will serve as a first step in mitigating the negative mental health effects of today’s social media platforms. A second concrete step will involve altering or eliminating said features by creating a social media platform that supports and even enhances mental well-being.

ContributorsGupta, Anay (Author) / Flores, Valerie (Thesis director) / Carrasquilla, Christina (Committee member) / Barnett, Jessica (Committee member) / The Sidney Poitier New American Film School (Contributor) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The COVID-19 pandemic has generated alarming increases in psychological distress and alcohol use behaviors and has caused the greatest increases in depression and anxiety symptoms among college students. Prior studies have examined the impact of COVID-19 broadly on mental health and alcohol use outcomes; however, few studies have examined these

The COVID-19 pandemic has generated alarming increases in psychological distress and alcohol use behaviors and has caused the greatest increases in depression and anxiety symptoms among college students. Prior studies have examined the impact of COVID-19 broadly on mental health and alcohol use outcomes; however, few studies have examined these impacts in college students. Previous studies have examined individual factors that could moderate the relation between COVID-19 related stressors and mental health and alcohol use outcomes, but knowledge is lacking regarding the role of emotion regulation. The present study aimed to examine the role of emotion regulation in the relation between both COVID-19 stressful experiences and COVID-19 related worry and mental health and alcohol use outcomes, and to explore racial/ethnic differences in their associations. Four hierarchical multiple regression models were conducted to assess main effects of COVID-19 stressors and emotion regulation, as well as moderation of the effect of emotion regulation on depression symptoms, anxiety symptoms, alcohol consumption, and alcohol use disorder (AUD) symptoms during the past year. COVID-19 related worry was associated with greater symptoms of both mental health outcomes, whereas COVID-19 related stressful experiences were associated with both mental health outcomes, more alcohol consumption, and more AUD symptoms. Difficulties in emotion regulation had significant main effects on mental health outcomes and AUD symptoms, but not alcohol consumption. Hispanic/Latinx students reported higher experiences of both COVID-19 related stressors, but consumed less alcohol than did White/European students. This study provides further insight into the nature of COVID-19 related stressors and their subsequent impacts. Implications for prevention and intervention on college campuses are discussed.

ContributorsConroy, Isobel (Author) / Su, Jinni (Thesis director) / Corbin, William (Committee member) / Doane, Leah (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor)
Created2021-12
Description

Suicide is a significant public health problem, with incidence rates and lethality continuing to increase yearly. Given the large human and financial cost of suicide worldwide alongside the lack of progress in suicide prediction, more research is needed to inform suicide prevention and intervention efforts. This study approaches suicide from

Suicide is a significant public health problem, with incidence rates and lethality continuing to increase yearly. Given the large human and financial cost of suicide worldwide alongside the lack of progress in suicide prediction, more research is needed to inform suicide prevention and intervention efforts. This study approaches suicide from the lens of suicide note-leaving behavior, which can provide important information on predictors of suicide. Specifically, this study adds to the existing literature on note-leaving by examining history of suicidality, mental health problems, and their interaction in predicting suicide note-leaving, in addition to demographic predictors of note-leaving examined in previous research using data from the National Violent Death Reporting System (NVDRS, n = 98,515). We fit a logistic regression model predicting leaving a suicide note or not, the results of which indicated that those with mental health problems or a history of suicidality were more likely to leave a suicide note than those without such histories, and those with both mental health problems and a history of suicidality were most likely to leave a suicide note. These findings reinforce the need to tailor suicide prevention efforts toward identifying and targeting higher risk populations.

ContributorsCarnesi, Gregory (Author) / O'Rourke, Holly (Thesis director) / Brewer, Gene (Committee member) / Corbin, William (Committee member) / Chassin, Laurie (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Watts College of Public Service & Community Solut (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor)
Created2022-05
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ContributorsCarnesi, Gregory (Author) / O'Rourke, Holly (Thesis director) / Brewer, Gene (Committee member) / Corbin, William (Committee member) / Chassin, Laurie (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2022-05
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ContributorsCarnesi, Gregory (Author) / O'Rourke, Holly (Thesis director) / Brewer, Gene (Committee member) / Corbin, William (Committee member) / Chassin, Laurie (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2022-05
Description
Hispanic/Latinx college students are at a greater risk for developing problematic alcohol use and negative mental health outcomes such as depression and anxiety because they experience contextual stressors (i.e., financial stress, academic stress, peer pressure) and cultural stressors (i.e., bicultural stress, acculturative stress, discrimination). Bicultural stress may be a risk

Hispanic/Latinx college students are at a greater risk for developing problematic alcohol use and negative mental health outcomes such as depression and anxiety because they experience contextual stressors (i.e., financial stress, academic stress, peer pressure) and cultural stressors (i.e., bicultural stress, acculturative stress, discrimination). Bicultural stress may be a risk factor for depressive, anxiety, and alcohol use disorder (AUD) symptoms. The cultural value of familism may play a protective role in Hispanic/Latinx college students. The purpose of this study was to investigate the effects of bicultural stress on depressive, anxiety, and AUD symptoms in first-year Hispanic/Latinx college students, and the role familism plays on moderating the relationship between bicultural stress and the outcomes. The sample was taken from the Pathways to College Health Study (N = 264; Female = 74.9%), which was survey administered via Qualtrics to first-year, Hispanic/Latinx college students at Arizona State University. The survey captured the participants’ levels of bicultural stress, familism, depressive, anxiety, and AUD symptoms. IBM SPSS Statistics was used for data analyses where three hierarchical regression models were run investigating the main effects and interaction effect of bicultural stress and familism. Results showed that higher levels of bicultural stress were associated with higher levels of mental health but were not associated with higher levels of AUD symptoms. Additionally, familism was not significantly associated with mental health or AUD symptoms suggesting familism may not play a substantial role in Hispanic/Latinx college students. There was no interaction found between familism and bicultural stress on the outcomes. These findings may aide in informing Hispanic/Latinx college students, universities, and clinicians on the impact bicultural stress may have on mental health outcomes.
ContributorsGhazoul, Marilyn (Author) / Su, Jinni (Thesis director) / Corbin, William (Committee member) / Cruz, Rick (Committee member) / Barrett, The Honors College (Contributor) / School of Art (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2023-12