Two symbolic events marked the start and the conclusion of the committee 's work on this report. First, the study's inception followed closely the conclusion of the Decade of the Brain, which yielded tremendous new insights into the development and workings of the nervous system. Second, the final stage of the preparation of this report for publication coincided with the publication of the two versions1 of the full sequence of the human genome, a landmark achievement that heralds a new era in our conceptualization of human biology and in our capacity to prevent and treat disease. Against this background of historic scientific breakthroughs, the enormous disparities between the developed and developing worlds in the understanding, prevention, and treatment of brain disorders become dramatically apparent. These disorders, which frequently lead to death and long-term disability, are undermining the development of low-income countries, despite the fact that many low-cost preventive and treatment interventions are known and feasible to implement. Brain disorders are highly prevalent in settings characterized by persistent poverty-driven conditions, such as malnutrition and AIDS, which also adversely affect the nervous system. The hidden epidemic of children's disabilities and the fact that 50 percent of the population in many developing countries is under 12 years of age add to the importance of placing brain disorders high on the agenda as a public health problem in all nations. This report seeks to provide evidence that it is in the self-
F.S. Collins and V.A. McKusick. Implications of the Human Genome Project for Medical Science. Journal of the American Medical Association Feb7;285(5):540-544, 2001.
interest of all governments to make a commitment to addressing brain disorders, building on the investments in health care they have already made.
ESTABLISHING NATIONAL AND LOCAL PRIORITIES FOR ADDRESSING BRAIN DISORDERS
In developing countries, the design and implementation of programs must be tailored to each country's needs and resources. The specific health needs of at-risk groups, resource constraints, the cultural context, and the local capacity to implement and sustain an intervention must all be taken into account. Building on evidence derived from programs in a variety of settings, this report highlights the need for rigorous operational research in conjunction with the provision of care. Several strategies for reducing the burden of brain disorders in the developing world emerged as this report was being prepared. Each requires further research for effective implementation based on consideration of the local resources and the community's health priorities.
THE POTENTIAL FOR PREVENTION
Prevention is critical in reducing the impact of brain disorders and in many instances is more cost-effective than treatment. Once established, impairment caused by these disorders is often irreversible. However, many potentially disabling disorders are now preventable. Examples include iodine supplementation to prevent mental retardation due to iodine deficiency; immunization against polio; folic acid supplementation and food fortification to reduce the number of children born with neural tube defects; and control of cysticercosis to prevent epilepsy. Appropriate, affordable treatment for other disorders, such as providing antidepressants or anticonvulsants, can prevent a lifetime of disability.
It is therefore essential to overcome existing barriers in developing countries to recognition of the public health importance of brain disorders and the development of strategies and programs for their prevention and treatment. Multifaceted research is needed to address these gaps, develop new prevention strategies, and assess the cost-effectiveness and sustainability of preventive strategies in specific settings. Multidisciplinary research involving collaboration between the health and social sciences and aiming to understand and remove these barriers should be targeted for increased funding.
INCREASING THE CLINICAL AND RESEARCH PROFESSIONAL CAPACITY IN DEVELOPING COUNTRIES
For a variety of historical, social, and economic reasons, many developing countries have a severe shortage of trained professionals with expertise in the
assessment, treatment, and rehabilitation of brain disorders. Increasing the clinical and research professional capacity in developing countries is key to developing sustainable local programs. The approaches to addressing these deficits highlighted in this report include the following:
Capacity building through on-site education, exchange programs, and distance learning using modern information technology;
Development of local networks that link centers with the requisite expertise to their surrounding community and creation of regional networks linking such centers through joint training programs, staff exchanges, and collaborative research; and
Partnerships between lead institutions in high-income countries and such collaborative networks in low-income countries.
COLLABORATIVE RESEARCH INTO GLOBAL HEALTH PROBLEMS
The demographic, cultural, and genetic diversity of populations in many developing countries offers unique opportunities for collaborative research addressing health issues of universal significance. For example, studies of Huntington's disease among a genetically unique population in Venezuela resulted in the identification of the responsible gene, an advance that will eventually lead to effective treatment. Similarly, epidemiological and genetic studies in Africa targeting the genetic basis of hypertension, conducted to complement similar studies in the United States and Europe, offer significant advantages in addressing the problem of stroke that will benefit all populations. A further example is research into the genetic basis and environmental factors associated with the good prognosis for schizophrenia in a substantial proportion of patients in developing countries. Both genetic (e.g., protective alleles) and environmental (psychosocial as well as dietary) factors may be involved, and collaborative research into this phenomenon holds promise for understanding key aspects of the etiology, treatment, and ultimate prevention of this debilitating disorder.
ACCESS TO AND AFFORDABILITY OF ESSENTIAL PHARMACEUTICAL PRODUCTS
In both the short and long terms, the availability and affordability of pharmaceutical products hold the key to important solutions for the treatment of brain disorders in the developing world. In most developing countries, the lack of adequate drug production facilities and the high prices of imported drugs restrict the availability of essential medicines. The medications needed to treat the disorders detailed in this report are simply not available on any scale in most low-income countries. However, the mere fact that the number of potential con-
sumers of pharmaceuticals in developing countries far exceeds those currently being treated should indicate to the major pharmaceutical and biotechnology companies that both major needs and major opportunities exist. Satisfactory ways can be found to reduce the disparities between the need and the severe economic limitations that deprive millions of people in developing countries of adequate treatment. Some options include the following:
Strengthening the research and development capacity in developing countries for local manufacturing of essential generic drugs that are cost-effective in the treatment of brain disorders.
Facilitating developing countries' access to, and ensuring the affordability of, newer central nervous system pharmaceuticals by linking price structure to per capita gross domestic product (GDP); utilizing subsidies from the World Bank, United Nations agencies, or other sources; and providing incentives for price reduction, such as extending the period of patent protection.
AN INVESTMENT IN FUTURE OPPORTUNITIES
There are many incentives for governments, research institutions, foundations, the World Bank, and nongovernmental organizations to make continued and sustained investments in ameliorating the impact of brain disorders in developing countries. While each of the disorders detailed in this report represents a highly significant problem, bipolar disorder, depression, developmental disabilities, epilepsy, schizophrenia, and stroke are just the tip of the iceberg. These and many other disorders have in common the fact that by severely affecting the ability of millions of people to function as productive members of their communities, they diminish the human and social capital of entire societies.
The contribution of good mental health and neurobehavioral functioning goes beyond the reduction of clinical symptoms and disability, improved workplace productivity, and the lost productivity of caregivers. There is evidence that individual and population-based interventions aimed at reducing brain disorders would enhance constructive social interaction and contribute to the building of social capital in a country. A particularly telling example is provided by recent research in Rwanda and Cambodia that demonstrated that an increase in individual attributes such as interpersonal communication, trust, and resilience is contributing to the rebuilding of the social fabric in the post-conflict development of these countries.
Brain disorders have a severe impact on the ability to earn, and they therefore contribute to the poverty cycle. It is important to consider both paid and unpaid work in this calculation, as both contribute to economic development. There is a gender differential, in virtually all countries with women carrying out the majority of unpaid work, but this differential is much more marked in developing as compared to developed countries. Since women tend to have a higher
prevalence of common disorders such as depression but are less likely to access treatment for such disorders, the actual negative impact of this gender disparity on the national economy is likely to be much greater than could be inferred from GDP and employment statistics.
Brain disorders also have an impact on key international health development targets, such as infant and child mortality. Child health improves when mothers are treated for depression, including postpartum depression. Reduced incidence of depression has proven links with better adherence to important health programs, such as antenatal care, vaccination, prevention and treatment of infectious diseases, and rehydration therapy for infant diarrhea.
Prevention and treatment of brain disorders can contribute significantly to the fundamental mission of a nation's health care system. Investment in these efforts proportional to the impact of brain disorders offers promise for building healthier, more productive communities and more prosperous nations. The success of innovative programs of treatment and research, coupled with recent initiatives and commitments from the international community, has created a favorable climate for meeting the challenge of brain disorders in developing countries.