Browsing by Author "Vorderstrasse, Allison A"
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Item Open Access Neurobiology of Insight in Schizophrenia: Interrelationships with Symptom Domains and Genetic Influences(2017) Xavier, Rose MaryProblem: Insight in schizophrenia broadly defined as an awareness into illness, symptoms and need for treatment, is a clinically important phenomenon because it is associated with a range of adverse outcomes such as longer duration of untreated psychosis, poor treatment adherence, frequent hospitalizations, increased risk for involuntary commitments, increased risk for violence towards self and others, and risk for treatment resistance. Such outcomes significantly add to the morbidity in patients with schizophrenia. Both good insight and impaired insight contribute to adverse clinical outcomes which imposes significant challenges in the clinical management of such patients. There is also a lack of clarity in insight’s complex relationship with other psychopathology symptoms and cognitive domains which adds to the challenges. Thus, a neurobiological approach examining the etiological mechanisms of insight that lead to insight variations and the clinical outcomes associated with it, is critical to develop precise, effective and clinically meaningful interventions.
A systematic review of the neurobiological basis of insight identified a number of neuroimaging studies that examined the etiology of insight. Such studies identified shared and unique neural correlates for different insight dimensions. Only three studies examined insight at a cellular level and found that impaired insight was associated with reduced oligodendrocytes clusters in parietal lobe regions. No studies had examined a genetic or molecular basis of insight despite evidence supporting the heritable and trait like properties of insight. The goal of this dissertation was to develop knowledge on the neurobiological basis of insight in schizophrenia. Specifically, we examined (1) the interrelationships among insight, psychopathology symptoms and cognitive domains (2) associations of a validated schizophrenia polygenic risk score with insight, psychopathology symptoms and cognitive domains and (3) associations of candidate gene associations with insight, psychopathology symptoms and cognitive domains.
Methods: We first conducted a cross sectional analyses (N=1391) of clinical data to examine interrelationships among insight dimensions (illness and treatment insight), psychopathology symptom dimensions (positive, negative disorganized, excited and depressed) and cognitive domains using baseline data from the Clinical Antipsychotics Trial of Intervention Effectiveness (CATIE). Structural equation modeling was implemented to examine the direct and indirect effects among variables to identify causal relational paths. Next, in the sample of CATIE patients with genetic data (N= 741) we tested if genetic susceptibility to schizophrenia measured as a schizophrenia polygenic risk score (PRS) could predict insight, psychopathology symptoms and cognitive performance. Finally, we tested if there were specific candidate genes within the well validated schizophrenia autosomal loci associated with insight, psychopathology symptoms and cognitive performance. Given the association of reduced oligodendrocyte cell clusters with insight, we also examined whether a set of 11 schizophrenia related oligodendrocyte genes were associated with insight.
Results: From our cross-sectional analysis of clinical data we found that positive, depressed and disorganized symptoms were associated with illness insight, with the strongest effect for disorganized symptoms. Illness insight exerted a mediation effect between these symptoms and treatment insight. A small mediating effect of neurocognition was observed between (1) disorganized symptoms and treatment insight and (2) depressed symptoms and treatment insight. Contradictory to previous studies we did not see a relationship between negative symptoms and insight dimensions.
We found strong evidence for polygenic burden predicting insight. PRS associations were significant for overall insight (R2 = 0.005), treatment insight dimension (R2 = 0.005) and the poor insight group (Nagelkerke’s R2 = 0.032) in our analyses. We also found significant association of variants rs320073, an intergenic variant and rs1479165 in the SOX2-OT gene for poor insight. Five of the top hit SNPs among 2487 SNPs tested were in the SOX2-OT gene.
PRS associations were significant only for negative and positive symptoms explaining 0.5% and 0.7% of the variance respectively. We did not identify any significant candidate genes associated with symptoms. PRS did not predict neurocognitive composite measure and social cognitive measure in our sample. However, neurocognitive subdomains of working memory (R2= 0.006) and vigilance (R2 = 0.008) was significantly predicted by PRS but these did not survive permutation correction.
Conclusion: In our clinical data we have clarified some of the complexity of insight’s relationship with symptom and cognitive domains. Our findings suggest shared and unique paths for insight dimensions and highlights the mediation effects of neurocognition on specific symptoms and treatment insight. Further studies designed to examine these potential causal relationships are needed.
In our genetic data, we found a strong polygenic signal and a specific candidate gene association with SOX2-OT for poor insight. Polygenic signal for treatment insight but not illness insight suggests differences in biological mechanisms for different insight dimensions. To the best of our knowledge, this is the first study to provide molecular genetic evidence for insight variations in schizophrenia.
We also replicated known associations of schizophrenia PRS with negative symptoms and neurocognitive domains of working memory and vigilance in our sample of patients with chronic schizophrenia. A significant PRS prediction for positive symptoms in our chronic sample offers an avenue for further study. These findings have implications for future research and potentially clinical practice. The approach of investigating the biological basis of symptoms which are tied to long term adverse outcomes have the potential to help identify precise and effective treatments in patients afflicted with schizophrenia.
Item Open Access Renal Disease Risk and Risk Perceptions Among African-American Women with Type 2 Diabetes(2015) Migliore, Casey LynnAbstract
Problem: African Americans face a disparate risk for renal disease development secondary to type 2 diabetes (T2D), and African-American women have shown to be at the highest risk. Despite this, there is minimal research on African American's awareness of renal disease and existing renal disease risk perceptions, and none focused specifically on African-American women with T2D. Although the literature has shown that a portion of this disparate risk is due to modifiable social and cultural factors, there is still a significant amount of unexplained risk. Since past research has shown that risk perceptions can influence preventative behaviors, it is important to gain an in-depth understanding of renal disease beliefs and existing risk perceptions among high-risk African-American women with T2D. Once risk perceptions are better understood in this population, interventions can be developed to correct inaccurate beliefs and risk perceptions and aim to decrease renal disease risk.
Methods: Three different methods of analyses were employed in this dissertation, including: 1) a systematic review of the literature, 2) an exploratory, descriptive, qualitative study, and 3) a quantitative secondary analysis, including descriptive statistics, a cluster analysis and mixed modeling. The Common Sense Model guided all three studies and these three methods of evaluation helped us to gain a more complete understanding of renal disease risk perceptions in African Americans, particularly African-American women with T2D, and provided guidance for future intervention research in this population.
Conclusions: The findings of this dissertation illustrated there is a significant gap in the literature on African American's renal disease awareness and risk perceptions, yet the available research was used to guide the in-depth interviews with African-American women with T2D. Overall, African Americans underestimate their renal disease risk and lack an understanding of the disease, even in the presence of risk factors. African-American women, in particular, related renal disease directly to the end-stages of the disease, perceived a greater risk for other complications of diabetes, and exhibited significant fear related to their perceived consequences of the disease. This fear frequently initiated maladaptive coping mechanisms, which influenced risk perceptions negatively and hindered preventative behaviors. This study also found that health care providers rarely discussed the disease and often exhibited provider control. Therefore, these findings suggest an urgent need for clinical practice suggestions and intervention research aimed at correcting inaccurate risk perceptions. The secondary analysis findings showed that a culturally relevant intervention with coping skills training resulted in significant improvements in renal disease risk factors among high-risk African-American women with T2D; however, we cannot be sure which facets of the intervention or control care for equal attention may have influenced these outcomes, and renal disease beliefs and risk perceptions were not assessed in the parent study. Therefore, the knowledge gained from this dissertation can be used to guide intervention research that evaluates change over time in renal disease risk representations, risk perceptions, coping procedures and outcomes among participants at high-risk for renal disease.
Item Open Access Social Interaction and Support in a Type 2 Diabetes Computer-Mediated Environment(2017) Lewinski, Allison AnnProblem:
Type 2 diabetes (T2D) is increasing in incidence and prevalence in the United States, and T2D remains the 7th leading cause of death. Consistent T2D self-management delays the onset of co-morbidities associated with this disease; however rates of self-management in adults living with T2D remain sub-optimal. The literature indicates that frequent and sustained social interaction between an individual living with T2D, and other peers living with T2D and a healthcare provider, helps sustain critical self-management behaviors. Yet, an individual living with T2D may experience challenges in obtaining this helpful interaction and support due to temporal, geographical, or physical limitations.
Computer mediated environments (CMEs; programs via the Internet) facilitate the exchange of T2D-specific information and support, and may ameliorate limitations to obtaining support and information. CMEs facilitate the creation of an online community in which individuals can choose their participation and the amount of personal information they reveal to other individuals. These personal narratives facilitate the exchange of support and reinforcement as individuals reveal personal challenges and successes encountered during daily T2D self-management. Yet, interventions via CMEs aimed at increasing self-management in individuals living with T2D, have shown mixed results for sustained behavior change. One way to improve disease-specific CMEs is to understand how individuals interact with others in these CMEs.
This study used Strong/Weak Ties Theory and Social Penetration Theory to describe the frequency and content of social interaction and support in a CME. In Strong/Weak Ties Theory, tie strength is defined as time in which the relationship can develop and occur, the intensity of emotions within that relationship, the breadth and depth of intimacy, and whether the relationship is reciprocal and mutual. Social Penetration Theory purports that the perceived value of a relationship influences the breadth (number of topics discussed) and depth (degree of intimacy and personalization of discussed topics) of a relationship. This study defined social support using the four types of support commonly identified in the literature: emotional, instrumental, appraisal, and informational. Therefore, the overall purpose of this study was to develop knowledge to advance the science of social relationships in CMEs, with a focus on characterizing social interaction and social support as they relate to self-management in a chronic disease. In particular, knowledge was developed about how social interaction and social support among adults living with T2D was exchanged in a CME.
Materials:
This study was a secondary analysis of qualitative data collected from the Second Life Impacts Diabetes Education & Self-Management (SLIDES) study. The SLIDES study provided self-management knowledge and support via a CME to individuals living with T2D. These data included recorded synchronous (i.e., real-time) and asynchronous (i.e., delay present) conversations among study participants (n = 20) and diabetes educators and study investigators (n = 4). Diabetes educators offered two education sessions and one support session per week, and these sessions were opportunities for participants to ask questions, learn about T2D, and interact with other participants who had T2D. During the study, all conversational data (i.e., synchronous conversations and text-chat; asynchronous emails and discussion board posts) among study participants, diabetes educators, and study staff within the CME were recorded to MP3 files and stored on a secure server at the University.
The conversational data used in the analysis was prepared over a period of several months; this attention to detail enabled a rich description of social interaction and support in a CME. The researcher listened to the MP3 files and then transcribed several files (n = 164) in order to gain knowledge of the SLIDES CME. A professional transcription service transcribed the remaining MP3 files (n = 697). The researcher cleaned all transcribed conversations by simultaneously listening to the MP3 files (n = 861) and reading the transcribed text to verify accuracy. Then, a systematic approach was used to link each spoken word to a SLIDES participant by voice recognition or reference to names to determine which participants contributed to, and how much each participant engaged in, a conversation. Once the researcher reviewed all MP3 files and transcribed text for accuracy, the Microsoft Word document (n = 1,537 pages) was imported into Atlas.ti to support coding and analysis.
Methods:
The primary study used a qualitative study design to comprehensively describe conversational data from participants who engaged in a CME that focused on T2D. Qualitative content analysis guided the description of social interaction and social support. The researcher developed inductive and deductive codes to describe social interaction and social support based upon the guiding framework. A research team comprised of a PhD candidate and two research experts reviewed all emergent codes and themes during first and second level coding.
Results:
Findings from the primary study describe social interaction and social support among individuals who interacted in a CME. Four characteristics of a social interaction in a CME developed: (1) communication techniques, or how participants interact in real-time communication in a CME; (2) expressions of self-management, or the content of participants’ self-management discussions; (3) depth of conversation, or intensity of personal information shared; and (4) breadth of conversation, or the number of topics discussed among participants in a conversation. The findings illustrate that the four types of social support are present in a CME: (1) instrumental support, or the exchange T2D-specific tangible goods in the CME; (2) appraisal support, or the exchange of affirmational support for T2D self-management behaviors; (3) informational support, or the exchange of T2D-specific information; and (4) emotional support, or the exchange of empathy among participants in a conversation. Additionally, the findings illustrate the elicitation behaviors (i.e., prompts that individuals used to obtain support) and the support responses (i.e., the support provided) to further describe social support.
A social interaction in a CME is a multidimensional construct because the communication medium (i.e., the CME) influences the communication techniques individuals’ use when talking amongst themselves to exchange information and support. The findings indicated that participants will reveal personal information about themselves in a CME, and most of the topics discussed are salient to T2D. The primary study indicated that strong/weak ties between individuals exist in CME relationships, and these ties develop over time with the sharing of personal information. The ties developed among (1) diabetes educators and individuals living with T2D, and (2) individuals living with T2D. The findings from this study indicate that social interaction and social support are exchanged among peers and providers in a CME.
Conclusion:
Computer-mediated environments enable persons living with T2D to obtain valuable interaction and support at times and locations that are convenient. Type 2 diabetes self-management is person-specific and dynamic, which highlights the need for social support that is personalized and timely. One way participants received personalized support and information was through interactions with the diabetes educators and other participants. The interactions in a CME mirrored those in a face-to-face environment as participants asked questions of each other, responded to other participants, talked about personal challenges, and provided information. This study began to characterize the social interactions among persons living with T2D who interacted in a CME. Future research on the characterization of social interactions in a CME should focus on analyzing social interactions in a larger, more diverse sample that includes men and women of diverse ages, races, ethnicities, education levels, and income levels.