Sickle Cell Disease and Food Addiction as Potential Contributors to the Racial Disparity in Cognitive and Behavioral Deficits in Young and Middle-Aged Black Americans Restricted; Files Only
Hardy, Raven (Fall 2021)
Abstract
Cognitive and behavioral disparities have been observed in Black Americans when compared to non-Hispanic Whites. Black Americans have higher rates of chronic illness which, in part, contribute to the observed cognitive and behavioral disparities. While chronic disorders, such as cardiovascular disease and sickle cell disease (SCD), have been suggested to contribute to cognitive and behavioral impairments for Black Americans, other disorders that potentially contribute to the observed cognitive and behavioral disparity, such as eating disorders, have been understudied. Food addiction, an unspecified eating disorder, is associated with cognitive and behavioral impairments in general populations, but it is unclear whether this disorder contributes to cognitive and behavioral impairments in Black Americans. Additionally, there is limited data on the mechanisms contributing to disorders that disproportionately impact Black Americans and are associated with cognitive and behavioral abnormalities, such as SCD, which could serve as drivers for observed cognitive and behavioral disparities. This dissertation aims to determine whether two disparate disorders, SCD, and food addiction, potentially contribute to the cognitive and neurobehavioral disparity observed in Black Americans and to understand potential mechanisms underlying these disparities. We examined the contribution of SCD and food addiction to the development of cognitive and behavioral abnormalities utilizing a mouse model of SCD and a Black American population, respectively. SCD and food addiction were associated with cognitive and behavioral impairments, specifically higher levels of depression and anxiety and executive function impairments. We next examined whether age, neuroinflammation, and neuroplasticity (dendritic alterations) contributed to cognitive and behavioral impairments in SCD. In comparison to controls, cognitive and behavioral impairments associated with SCD were age-dependent and were associated with higher levels of neuroinflammation and abnormal neuroplasticity. Given that high levels of neuroinflammation and abnormal plasticity were observed to contribute to cognitive and behavioral impairments in SCD, we administered a pharmacologic intervention, a minocycline treatment, to determine whether treatment could impact neuroplasticity and neuroinflammation processes and improve cognitive and behavioral impairments. Minocycline treatment in SCD restored observed cognitive and behavioral impairments, reduced neuroinflammation, and improved neuroplasticity. These results provide evidence that SCD and food addiction contribute to cognitive and behavioral impairments and potentially contribute to the cognitive and behavioral disparity observed in Black Americans. The results also provide evidence that neuroinflammation and abnormal neuroplasticity contribute to the development of cognitive and behavioral impairments and could serve as potential drivers for cognitive and behavioral disparities observed in Black Americans.
Table of Contents
CHAPTER 1. INTRODUCTION 1
INTRODUCTION 2
1.1 SICKLE CELL DISEASE AND EATING DISORDERS ARE CHRONIC CONDITIONS THAT ARE ASSOCIATED WITH COGNITIVE AND NEUROBEHAVIORAL IMPAIRMENTS
IN BLACK AMERICANS 2
1.2 SICKLE CELL DISEASE 3
1.2.1 PREVALENCE AND BURDEN OF SICKLE CELL DISEASE 3
1.2.2 SICKLE CELL DISEASE - A GROUP OF INHERITED DISEASES 4
1.2.3 PATHOPHYSIOLOGICAL MECHANISM OF SICKLE CELL DISEASE 5
1.3 FOOD ADDICTION - AN UNSPECIFIED EATING DISORDER 7
1.3.1 EATING DISORDERS IN BLACK AMERICANS 7
1.3.2 FOOD ADDICTION 8
1.3.3 PATHOBIOLOGY ASSOCIATED WITH FOOD ADDICTION 10
1.4 NEUROBEHAVIORAL IMPAIRMENT IN SICKLE CELL DISEASE AND FOOD ADDICTION 12
1.5 COGNITIVE IMPAIRMENTS IN SICKLE CELL DISEASE AND FOOD ADDICTION 13
1.6 NEURONAL CHANGES ASSOCIATED WITH COGNITIVE AND NEUROBEHAVIORAL IMPAIRMENTS IN SICKLE CELL DISEASE 15
1.6.1 ASSOCIATIONS BETWEEN STROKE WITH SICKLE CELL DISEASE AND FOOD ADDICTION 16
1.6.2 WHITE MATTER CONNECTIVITY - SICKLE CELL AND FOOD ADDICTION 17
1.7 NEUROINFLAMMATION IN SICKLE CELL DISEASE AND FOOD ADDICTION 19
1.8 SICKLE CELL DISEASE AND FOOD ADDICTION: DISPARATE DISORDERS CONTRIBUTING TO COGNITIVE AND BEHAVIORAL IMPAIRMENTS 21
1.9 DISSERTATION OVERVIEW 23
CHAPTER 2: ROLE OF AGE AND NEUROINFLAMMATION IN THE MECHANISM OF COGNITIVE DEFICITS IN SICKLE 26
ACKNOWLEDGEMENT OF REPRODUCTION 27
2.1 ABSTRACT 28
2.2 INTRODUCTION 30
2.3 METHODS 33
2.3.1 ANIMAL PREPARATION 33
2.3.2 STUDY DESIGN AND OVERALL METHODS 34
2.3.3 MINOCYCLINE TREATMENT 36
2.3.4 NOVEL OBJECT RECOGNITION (NOR) TEST 36
2.3.5 FEAR CONDITIONING TEST 37
2.3.6 IMMUNOHISTOCHEMISTRY 38
2.3.7 QUANTIFICATION OF DENDRITE ARBORS, DENDRITIC SPINE DENSITY AND SPINE MORPHOLOGY 42
2.3.8 STATISTICAL ANALYSIS 43
2.4 RESULTS 44
2.4.1 AGED SICKLE CELL MICE DISPLAYED SIGNIFICANT COGNITIVE AND BEHAVIORAL DEFICITS COMPARED TO CONTROL MICE 44
2.4.2 AGED SICKLE CELL MICE DISPLAYED SIGNIFICANT COGNITIVE AND BEHAVIORAL DEFICITS THAT WERE NOT SEEN IN YOUNGER SICKLE CELL MICE 44
2.4.3 AGED SICKLE CELL MICE HAVE MORE EVIDENCE OF NEUROINFLAMMATION COMPARED TO CONTROLS 45
2.4.4 AGED SICKLE CELL MICE HAVE LOWER DENDRITIC SPINE DENSITY COMPARED TO CONTROLS 45
2.4.5 TREATMENT WITH MINOCYCLINE RESTORED COGNITIVE AND BEHAVIORAL DEFICIT IN AGED SICKLE CELL MICE 46
2.4.6 TREATMENT WITH MINOCYCLINE ATTENUATES NEUROINFLAMMATION IN SICKLE CELL MICE 47
2.4.7 SICKLE CELL MICE TREATED WITH MINOCYCLINE SHOWED IMPROVEMENT IN NEUROPLASTICITY AND POTENTIALLY NEUROGENESIS 48
2.4.8 COGNITIVE AND BEHAVIORAL DEFICITS BEGIN TO EMERGE AT 11-MONTHS AND BEGIN TO PLATEAU AT 18-MONTHS 50
2.5 DISCUSSION 53
CHAPTER 3: FOOD ADDICTION AND SUBSTANCE ADDICTION IN BLACK WOMEN: COMMON CLINICAL CHARACTERISTICS 66
ACKNOWLEDGEMENT OF REPRODUCTION 67
3.1 ABSTRACT 68
3.2 INTRODUCTION 69
3.3 METHODS 72
3.3.1 SUBJECTS 72
3.3.2 MEASURES 72
3.3.2.1 DEMOGRAPHIC INFORMATION 72
3.3.2.2 MALADAPTIVE EATING ASSESSMENTS 73
3.3.2.3 TRAUMA ASSESSMENTS 73
3.3.2.4 BEHAVIORAL ASSESSMENTS 74
3.3.2.5 COGNITIVE ASSESSMENTS 75
3.3.2.6 ASSESSMENTS FOR SUBSTANCE USE DISORDER 78
3.3.3 STATISTICAL ANALYSIS 78
3.4 RESULTS 79
3.4.1 DEMOGRAPHICS 79
3.4.2 EMOTIONAL EATING AND PSYCHOPATHOLOGY 79
3.4.3 EMOTIONAL DYSREGULATION 80
3.4.4 DISSOCIATIVE SYMPTOMOLOGY 80
3.4.5 TRAUMA EXPOSURE 81
3.4.6 COGNITION 82
3.5 DISCUSSION 83
CHAPTER 4: DISCUSSION 102
DISCUSSION 103
4.1 SUMMARY OF RESULTS 104
4.1.1 SUMMARY OF CHAPTER 2 104
4.1.2 SUMMARY OF CHAPTER 3 107
4.2 INTEGRATION OF RESULTS 108
4.3 CONCLUSIONS AND FUTURE DIRECTIONS 112
4.3.1 SICKLE CELL DISEASE - COGNITIVE AND NEUROBEHAVIORAL CLINICAL GAPS AND FUTURE DIRECTIONS 114
4.3.2 CONTRIBUTION TO HEALTH DISPARITIES FOR BLACK AMERICANS 115
4.4 LIMITATIONS 117
CHAPTER 5: REFERENCES 119
APPENDIX 1: SUPPLEMENTARY INFORMATION FOR CHAPTER 1 208
APPENDIX 2: SUPPLEMENTARY DATA FOR CHAPTER 2 210
ABBREVIATIONS LIST 218
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