Goldie S. Byrd

Recruiting intergenerational African American males for biomedical research studies: A major research challenge

The health and well-being of all individuals, independent of race, ethnicity, or gender, is a significant public health concern. Despite many improvements in the status of minority health, African American males continue to have the highest age-adjusted mortality rate of any race-sex group in the United States. Such disparities are accounted for by deaths from a number of diseases such as diabetes, human immunodeficiency virus (HIV), cancer, and cardiovascular disease, as well as by many historical and present social and cultural constructs that present as obstacles to better health outcomes. Distrust of the medical community, inadequate education, low socioeconomic status, social deprivation, and underutilized primary health care services all contribute to disproportionate health and health care outcomes among African Americans compared to their Caucasian counterparts. Results of clinical research on diseases that disproportionately affect African American males are often limited in their reliability due to common sampling errors existing in the majority of biomedical research studies and clinical trials. There are many reasons for underrepresentation of African American males in clinical trials, including their common recollection and interpretation of relevant historical of biomedical events where minorities were abused or exposed to racial discrimination or racist provocation. In addition, African American males continue to be less educated and more disenfranchised from the majority in society than Caucasian males and females and their African American female counterparts. As such, understanding their perceptions, even in early developmental years, about health and obstacles to involvement in research is important. In an effort to understand perspectives about their level of participation, motivation for participation, impact of education, and engagement in research, this study was designed to explore factors that impact their willingness to participate. Our research suggests that: (1) African American males across all ages are willing to participate in several types of research studies, even those that require human samples; (2) their level of participation is significantly influenced by education level; and (3) their decision to participate in research studies is motivated by civic duty, monetary compensation, and whether they or a relative has had the disease of interest. However, African American males, across all age groups, continue to report a lack of trust as a primary reason for their unwillingness to participate in biomedical research. There is an ongoing need to continue to seek advice, improve communication, and design research studies that garner trust and improve participation among African American males as a targeted underrepresented population. Such communication and dialogues should occur at all age levels of research development to assess. current attitudes and behaviors of African American males around participation.

Repeat expansions in the C9ORF72 gene contribute to Alzheimer's disease in Caucasians

Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimers disease (AD), we hypothesized that C9ORF72 expansions might contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a proportion of 0.76% in AD cases versus 0 in control subjects (p = 3.3E-03; 1182 cases, 1039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0-23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological re-evaluation of identified C9ORF72 expansion carriers revealed 9 clinical and/or autopsy confirmed AD and 2 FTD final diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD.

Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

Less is known about the genetic basis of Alzheimers disease (AD) in African Americans (AAs) than in non‐Hispanic whites.

African American Participation in Health-Related Research Studies: Indicators for Effective Recruitment

OBJECTIVE To elucidate factors that influence African American willingness to participate in health-related research studies. METHODS The African American Alzheimer disease research study group at North Carolina A&T State University designed an in-person questionnaire and surveyed more than 700 African American adults on their willingness to participate in health-related research studies. The questionnaire was distributed and collected in a nonclinical setting during the years 2008 and 2009. This study was approved by the North Carolina A&T State University Institutional Review Board. RESULTS Of the 733 valid respondents, 16% had previously participated in a health-related research study. Of these, more than 90% were willing to participate again in future research studies. Of the 614 who had never participated in a research study, more than 70% expressed willingness to participate. The majority (75%) of experienced research study participants (RSP) were older than 40 years compared with 45% of non-research study participants. Experienced research participants were also twice as likely to have a college degree compared with non-research study participants. Seventy-three percent of non-research study participants were willing to participate in research studies in the future. The factors that were probable impediments to participation included lack of time and trust. Men with knowledge of the Tuskegee Syphilis Study were 50% less likely to be willing to participate compared with those who had not heard of Tuskegee Syphilis Study. CONCLUSIONS African Americans are willing to participate in health-related research studies. Several factors such as the appropriate incentives, community trust building, outreach, and community partnership creation are necessary for engaging minority participants. Incorporating factors that target African American enrollment in research design and implementation, such as increased training of minority health ambassadors and African American researchers and public health specialists, are needed to better engage minorities across generations, in research.

Depression, Suicidal Ideation, and Attempts in Black Patients With Sickle Cell Disease

There is a strong relationship between suicidal ideation, suicide attempts, and depression. Rates of successful suicides are relatively high among the chronically ill compared to other populations but are reduced with treatment. Depression and suicide rates also often differ among blacks as compared to other populations. Using survey methods, we evaluated self-reported rates of depression, suicidal ideation, and suicide attempts in 30 male and 37 female black patients with sickle cell disease (SCD). SCD is a condition characterized by chronic, unpredictable pains and psychosocial distress. Thirty-six percent of the sample self-reported depression in the past 30 days, while 22 percent of the sample exhibited scores on the Beck Depression Inventory indicative of mild or greater depression (mean BDI, 8.31 +/- 7.79). Twenty-nine percent of patients indicated an episode of suicidal ideation and 8%, a suicidal attempt in their lifetime. Thirty-three percent reported treatment by a mental health professional. We conclude that there is a continuing need for mental health services in the management of depressed affect and risk for suicide among patients with SCD. Standards of clinical care must remain flexible to accommodate the mental health needs of this population of patients.

Fear of movement (kinesiophobia), pain, and psychopathology in patients with sickle cell disease.

ObjectivesFear of movement (ie, kinesiophobia) has emerged as a significant predictor of pain-related outcomes including disability and psychologic distress across various types of pain (eg, back pain, headache, fibromyalgia, complex regional pain syndrome). However, no research has examined the prevalence of kinesiophobia in adults with sickle cell disease (SCD). The purpose of this study was to assess the degree of kinesiophobia reported by African American men and women with SCD and to determine whether kinesiophobia is related to pain and psychologic distress in this population. MethodsSixty-seven men and women with SCD recruited from a comprehensive sickle cell treatment program in a large academic medical center completed questionnaires that assess fear of movement, pain and pain interference, and psychologic distress. ResultsParticipants reported levels of kinesiophobia (M=30.48, SD=7.55) that were comparable to those obtained for patients with low back pain and fibromyalgia. Although pain levels did not differ by sex, men reported greater kinesiophobia than women (P=0.02). As hypothesized, higher levels of kinesiophobia were associated with greater psychologic distress, particularly Phobic Anxiety (r=0.35), Psychoticism (r=0.29), Somatization (r=0.45), Anxiety (r=0.35), Obsessive-compulsive (r=0.34), Interpersonal Sensitivity (r=0.25), Depression (r=0.29), and all 3 summary indices of the SCL-90-R (all Ps<0.05). DiscussionAlthough and historically, pain associated with SCD has not been considered in the context of fear of movement, findings suggest that both kinesiophobia and sex are relevant constructs for consideration in understanding pain-related outcomes in SCD. Though our results require replication, this study suggests that greater kinesiophobia is associated with greater pain and psychologic distress.

Neuropsychological effects and attitudes in patients following electroconvulsive therapy

The current study examined the effects of electroconvulsive therapy (ECT) on neuropsychological test performance. Forty-six patients completed brief neuropsychological and psychological testing before and after receiving ECT for the treatment of recalcitrant and severe depression. Neuropsychological testing consisted of the Levin Selective Reminding Test (Levin) and Wechsler Memory Scale-Revised Edition (WMS-R). Self-report measures included the Beck Depression Inventory (BDI), the Short-Term Memory Questionnaire (STMQ), and several other measures of emotional functioning and patient attitudes toward ECT. The mean number of days between pre-ECT and post-ECT testing was 24. T-test revealed a significant decrease in subjective ratings of depression as rated by the BDI, t(45) = 9.82, P < 0.0001 (Pre-BDI = 27.9 ± 20.2; post-BDI = 13.5 ± 9.7). Objective ratings of memory appeared impaired following treatment, and patients’ self-report measures of memory confirmed this decline. More specifically, repeated measures MANOVA [Wilks Lambda F(11,30) = 4.3, p < 0.001] indicated significant decreases for measures of immediate recognition memory (p < 0.005), long-term storage (p < 0.05), delayed prose passage recall (p < 0.0001), percent retained of prose passages (p < 0.0001), and percent retained of visual designs (p < 0.0001). In addition, the number of double mentions on the Levin increased (p < 0.02). This study suggests that there may be a greater need to discuss the intermittent cognitive risks associated with ECT when obtaining informed consent prior to treatment. Further that self-reports of cognitive difficulties may persist even when depression has remitted. However, patients may not acknowledge or be aware of changes in their memory functioning, and post-ECT self-reports may not be reliable.

ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD.

Transethnic genome-wide scan identifies novel Alzheimer's disease loci

Genetic loci for Alzheimers disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.

Opioid Management and Dependency Among Adult Patients with Sickle Cell Disease

While pain is one of the most debilitating symptoms of sickle cell disease, narcotics remain an effective although controversial widely practiced intervention. Vaso-occlusive crises are the most common cause for seeking pharmacological treatment. The influence of stigmatization and pseudo addiction in emergency departments and outpatient clinics was reviewed. We analyzed patterns of narcotic utilization in a sample of 63 adult patients with sickle cell disease to determine if their psychological functioning and reports of pain differed as a function of the primary narcotics they were taking for oral pain management. Fifty-one percent of patients reported treatment of Oxycodone, 35% OxyContin, 24% methadone and 11% morphine. Patients who were treated with Oxycodone reported greater sensory reactions to pain (p = 0.001), visual analog scale (VAS) (p = 0.02), and averaged weekly pain intensity ratings than patients who did not use this medication. There were no differences in pain or affective response in patients treated with OxyContin, methadone or morphine. We suggest there are clear differences between the reports of pain in patients with sickle cell disease taking short-acting narcotics for pain management as compared to those who are not, a pattern that does not distinguish patients who are managed with long-acting preparations. We discuss the relevance of addressing narcotic management in the context of the perception of health care providers and patients with sickle cell disease.