The largest psychiatric genetics study ever done in Africa is increasing the diversity of data on mental illness, training a new generation of geneticists, and chipping away at the genetic underpinnings of schizophrenia and bipolar disorder.
By Tom Ulrich
It was not quite noon yet, but Mirembe had already had a long day. She had come to Butabika Hospital in Uganda early that morning, first to see a nurse and a doctor, and now stepped into a warm, sparsely-furnished office. Sitting down across the table from a research assistant, she wondered how long she was going to be there. But she was curious. The nurse had told her a little about a research study on mental illness and that she was eligible to participate if she agreed to sign up. She was full of questions.
Mirembe (not her real name) is one of tens of thousands of outpatients seen every year at Butabika, the national mental health hospital for all of Uganda, located on a hill on the outskirts of the capital city, Kampala. Over the next two hours, she would learn in detail what the research study was about and decide whether to participate. If she said yes, she would then answer more than 150 questions about her health, provide some of her saliva for DNA, and become one of more than 19,000 people across four African countries who, over the last two years, have signed on to help scientists in Africa, the United States, and beyond better understand the genetic roots of schizophrenia, bipolar disorder, and other psychiatric illnesses.
That effort, the Neuropsychiatric Genetics of African Populations-Psychosis (or NeuroGAP-Psychosis) project, is the largest study of psychiatric genetics ever conducted in Africa. Bringing together scientists and doctors from Uganda, Kenya, Ethiopia, South Africa, and the United States, the four-year-long project seeks to engage 35,000 Africans in a quest to gain a deeper biological understanding of schizophrenia and bipolar disorder across a diversity of populations.
We could be the first people to have 35,000 DNA samples in Africa. That’s huge.
Current genetic data on mental illness are mostly from people of European ancestry, and NeuroGAP-Psychosis aims to change that, by ensuring that African science and people are represented in the search for genetic markers for these diseases.
“The world is moving towards precision medicines,” said Dr. Dickens Akena, a psychiatrist and the NeuroGAP-Psychosis lead investigator in Uganda, and a psychiatry lecturer at Makerere University in Kampala. “If we’re going to make medications or diagnostics that are tailored towards certain genetic variations, then we need to include populations from Africa in the genetic data. If we don’t do that, the African continent and its inhabitants will be left behind.”
Until recently in Uganda, most children with sickle cell disease (SCD) never celebrated their fifth birthday—only 30% lived past this milestone. This low survival rate was mainly due to inadequate health care interventions for these children, plus lack of widespread newborn screening, explains Dr. Sarah Kiguli, a professor at Makerere University College of Health Sciences. Things are different today. Over the past decade, the East African nation has instituted a policy of screening newborns while strengthening strategies to manage their health. This means more children with SCD are growing into adolescence and adulthood.
Challenges still exist, says Kiguli. For example, the community and district facilities where many Ugandan children are born cannot provide comprehensive services, including newborn screening. Another issue: the risk of SCD complications related to kidneys, lungs, heart—almost all organs—grows higher as patients grow older, yet scientific research in Uganda hasn’t caught up with the reality of these longer lives. As a result, teens and adults with SCD don’t get “the care they deserve,” says Kiguli.
“It’s very painful for us pediatricians to see our patients encounter challenges and problems when they transition to adult care.”
Renewed research focus
Despite years devoted to children’s health, Kiguli believes it’s time to prioritize studies exploring appropriate SCD management in teens and adults. “We need solutions that address all the patients’ needs, including reproductive health, as they transition out of childhood.” She’s spearheaded a multidisciplinary research training program for researchers focused on the needs of people with SCD at all ages: Enhancing Research capacity for Sickle Cell Disease and related NCDs across the Lifespan in Uganda (ENRICH).
“Among our PhDs, we don’t have anyone from pediatrics—and that’s fine,” says Kiguli. Importantly, the researchers are trained as a group to amplify the benefits of multidisciplinary collaboration. “We’ve been working in silos—pediatricians alone, physicians alone, social scientists alone—that won’t help us address the comprehensive needs of these patients.”
Methodology has also been given sufficient consideration. “We provide both individual and team mentorship from the beginning,” said Kiguli. Monthly meetings help trainees develop personal development goals and career path plans in the hope they will continue in the field. The program also provides research training to health professionals, such as medical doctors, laboratory personnel, and nurses, who are not necessarily doing degree programs, “so those who manage patients routinely might also benefit,” said Kiguli.
South-to-South unity
For the project, Makerere University has partnered with Busitema University, located in eastern Uganda, where “prevalence of the sickle cell trait is as high as 20%,” says Kiguli. (Sickle cell trait refers to when a person has inherited one mutated allele of the sickle cell gene, not two.) This local prevalence contrasts with about 13% prevalence elsewhere in the country. Studying the disease in a high burden locale is highly relevant, because results may influence policy and treatment guidelines.
Kiguli has other reasons for collaborating with Busitema University, which is less than 15 years old. “We want to build capacity at this young institution since our colleagues there have less chance of doing research than we at Makerere do.” Working and supervising trainees together will give Busitema’s faculty much-needed experience, while providing opportunities for faculty at both universities to learn from each other. Kiguli also hopes the new collaboration will advance progress made as result of the universities’ past partnerships. “Capacity must be built in a sustainable way,” says Kiguli.
“It’s important to work collaboratively and not competitively—this is just as important for Makerere University as it is for Busitema University.”
ENRICH trainees talk about their projects
Dr. Jackline Akello
Dr. Jackline Akello, PhD candidate
My project is “Sickle cell disease in pregnancy: Experiences in provision and access to care and adverse pregnancy outcomes at Mbale and Kawempe Referral Hospitals.” As an obstetrician and gynecologist, I work as a lecturer at Makerere University and provide clinical care at the two national referral hospitals. I have encountered significant challenges in managing pregnant women with sickle cell disease (SCD) due to a number of healthcare navigation challenges. Additionally, the diverse cultural beliefs associated with SCD in Uganda affect access to care and ultimately outcome and quality of life for the patient.
By October, I will have started the enrolment of 161 pregnant women with confirmed SCD for my project. These participants will be followed throughout their pregnancies to track maternal and fetal complications, including stillbirths and low birth weight. Their experiences with the healthcare system will also be explored. As a Safe Motherhood champion, I have been focusing on hypertensive disorders in pregnancy, including pre-eclampsia, but this October at the Safe Motherhood Conference I will discuss the effects of SCD during pregnancy with the Ministry of Health. One of the endpoints of my study is to improve care for pregnant women who have SCD to enhance their pregnancy experience and outcomes.
Dr. George Paasi
Dr. George Paasi, PhD candidate
My project is “The Clinical Epidemiology, Spatiotemporal Patterns and Disease Modifiers of Severe Malaria among Children with Sickle Cell Disease in Eastern Uganda.” Uganda ranks fourth among countries with high burden of SCD and is in the top 10 with respect to malaria burden. Eastern Uganda has the highest burden of both diseases. My project addresses this dual burden of SCD and malaria in eastern Uganda—I want to decipher the SCD-malaria syndemic in this region.
I’m a medical doctor, I have a master’s in public health, and I just finished a fellowship in infectious disease, epidemiology, and biostatistics. I’ve worked at Mbale Clinical Research Institute for the last 10 years. Previously, I worked on an NIH-funded trial in Africa called Realizing Effectiveness Across Continents with Hydroxyurea (REACH) as a medical officer, and now I’m embarking on this PhD training. My hope is that the findings from my study will improve the identification of patients with SCD at risk of adverse outcomes when they get malaria. I also want to identify, through spatial temporal analysis, hotspot locations that require priority interventions. I also want to gain skills as an independent researcher in SCD and make a meaningful contribution to this field.
Dr. Anita Arinda
Dr. Anita Arinda, PhD candidate
My project is “Prevalence, associated factors, course and impact of major depressive disorder in adolescents with SCD in Mulago National Referral Hospital.” We have limited data on mental health of adolescents with SCD, so that’s why my project mainly looks at depression in adolescents (ages 10 to 17).
In our setting, we are fortunate that children with SCD live past their fifth birthday thanks to improved health care, but this presents new challenges. During adolescence, patients enter a crucial stage where they’re trying to develop their identity, yet they’re also beginning to understand the implications of their condition—that having this serious health condition cuts their life short. I want to understand their experiences. How does depression in adolescents with SCD differ from depression in adolescents without SCD? We know that sickle cell disease causes inflammation, so does that contribute to their depression? How does depression affect clinical outcomes, if at all?
If we can understand the underlying mechanisms of depression in teens with SCD, then we might find new ways to manage their care (as opposed to conventional treatment with antidepressants). I’ll do my research at Mulago National Referral Hospital, which has a clinic dedicated to children and teens with sickle cell disease. The clinic provides many services, but unfortunately no specialized mental health services. One day I hope that changes, so that children with SCD and depression can get help early.
Makerere University seeks to fill the position of Principal, College of Health Sciences. The College of Health Sciences is a semi-autonomous academic unit, which consists of Schools, Academic Institutes, Departments and Centers that carry out general and professional training, teaching, outreach and research in various disciplines.
Job description The Position is a Senior Post in the University created to give leadership to a College of Makerere University.
The Principal is the Chief Administrative, Academic and Financial Officer of the College and is responsible to the Vice Chancellor, University Senate and the University Council for promoting and maintaining academic excellence, efficiency and order of the College. Eligibility The person eligible for appointment should possess the following minimum attributes:
Hold a PhD or other academic Doctorate in one or more of the disciplines taught at the College;
Be at least at the rank of Associate Professor at the time of application;
At least four ( 4) years managerial expenence as a Head of an academic Department, Programmes Coordinator or a Research Project Manager in a University, Tertiary Institution or a reputable National Research Institution
Teaching experience of at least Six ( 6) years in one of the disciplines offered in the College he/she intends to lead;
Applicants who are at the rank of Associate Professor should not be above 61 years at the time of application.
Applicants who are at the rank of Professor should not be above 66 years at the time of application
Applicants must have demonstrable expenence of networking, research and resource mobilization. Applicants must attach evidence of resource mobilization and research conducted in the last five years.
Be a citizen of Uganda.
Tenure The Principal is appointed to hold office for a term of four years. Salary: Scale PU3 Mode of application:
i) Interested individuals should submit a letter of application accompanied with Curriculum Vitae, copies of relevant Academic Credentials and naming three referees;
ii) Applicants should make sure that at least two of the three referees have forwarded references concerning their application and suitability by the stated deadline;
iii) The deadline for submission of applications is 7th October 2024 at 5:00p.m. East African time.
Applications should be submitted to:
The University Secretary Makerere University Frank Kalimuzo Building, Study Room 4.1 P.O. Box 7062 Kampala, Uganda Or search.principals@mak.ac. ug
A very special welcome to the first edition of our newsletter of Makerere University’s Impact research capacity building program. The program is funded by a generous grant from the NIH Fogarty International Center to reduce the impact of rheumatic heart disease across all affected ages. For more than a decade Uganda has been at the fore front of rheumatic heart disease (RHD) research in sub-Saharan Africa. Building on that Foundation Makerere University College of Health Sciences decided it was opportune time to strengthen collaboration with Uganda Heart Institute and US partners: Cincinnati Children’s Hospital Medical Centre (CCHMC) and Children’s National Hospital (CNH) to uplift Uganda’s research capacity to innovate and generate knowledge critical for elimination of rheumatic fever and rheumatic heart disease in the long run.
Whereas doctoral training of doctors and nurses is the main focus of our capacity strengthening initiatives, other levels are not left behind. Training is concurrently ongoing at master’s degree level and in-service for health professionals to better their research careers. The training spots were nationally advertised publicly and recruitment of trainees was competitive. Major research activities are taking place in rural communities in which rheumatic fever is relatively common. The program puts emphasis on community engagement so that the public can understand the importance and centrality of their actions in the control and elimination of rheumatic fever and achieving better quality of life and survival of those having rheumatic heart disease and its complications. The program pays special attention to gender issues in the research we do.
Prof. Emeritus Nelson Sewankambo PRINCIPAL INVESTIGATOR