Last month, stories reporting on Minority Mental Health Awareness Month focused mainly on minority access to healthcare or addressing stigma that exists in some minority communities in treating psychiatric problems. In the end, mental health and physical health are joined at the hip, and failing to address either can exacerbate problems in the other.
While social challenges to address mental health in minority communities is very important, the media generally missed that a federal priority for improving minority mental health is to include more participants across diverse racial backgrounds in research. Broadening the genetic pool in psychiatric studies will increase our understanding of the biological mechanisms that might be leading to disparities in mental health outcomes in different groups. This research can then be leveraged to ensure that future mental health interventions are evidence based and tailored to all Americans.
At the Lieber Institute for Brain Development, we study the brains of deceased people, examining specific brain regions for genetic and molecular differences that can explain why some people have psychiatric diseases such as depression, schizophrenia or PTSD. Because comparing genetic differences across racial groups can be useful in uncovering these biological mechanisms, we have begun expanding our brain bank to add specimens from individuals of diverse ethnic backgrounds.
Although most of the brains in our collection come from people with European ancestry, more than 700 have been donated from African Americans, making us the brain repository with a uniquely large collection of African-American donors. This happened mostly by chance. To collect donations, we work with families and medical examiners, and most of the donations come from Maryland, which has a high population of African Americans. To ensure we have a more diverse collection from other racial groups, we also have collaborations with groups in other parts of the country. From Kalamazoo Michigan, a site we established in 2016, we receive donations mainly from individuals of European ancestry.
In late 2017, we established two new collection sites. From a site in North Dakota, we expect that around 10% of the donations we gather there will come from the indigenous continental population. Our fourth site is a collaboration with the medical examiner in Santa Clara County in California which serves a diverse population, with large numbers of East Asians, South Asians, and Hispanics.
While we don’t yet have psychiatric therapies that target different genetic groups, we know that genetic difference can be important in medicine. Genetics explain why Europeans from the north are taller than those from the South and why Whites in America are more likely to suffer from multiple sclerosis than Blacks, while the opposite is true about end-stage kidney disease and Alzheimer’s Disease. Multiple diseases caused by recessive genes have been identified as founder effects in South Asia. Only now have researchers begun to understand that within one billion people in India, there are dozens of distinct genetic groups, offering .opportunities for individualized medicine even within a seemingly single population
Similar issues hold true for alcoholism — which some people still do not acknowledge is a mental health disorder, like all addictions. Research by the National Institutes of Health has found that two key enzymes — alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) — play a key role in how alcohol is metabolized. Genetic differences in these enzymes vary in Asians and may help to explain why some groups have higher or lower rates of alcohol-related problems. For example, relatively high rates of alcohol dependence have been found among Korean Americans, whereas relatively low rates have been found in Chinese Americans.
It is becoming increasingly clear that failing to acknowledge genetic differences can affect patient treatment. In 2014, the state of Hawaii sued drug manufacturers for not disclosing that the blood thinner Plavix was less effective for some patients of East Asian or Pacific Islander descent. The drug’s label now warns Chinese patients that they are more likely to have a gene variant that makes the drug ineffective. In a second example, researchers discovered that a commonly used asthma medication is less effective for African-American and Puerto Rican children as for European American or Mexican children.
Hopefully, the NIH’s requirement to include more minorities in research will help us better understand how genetic differences might be causing differences in health outcomes. In 2014, the FDA also began supporting industry efforts to improve diversity in clinical trials, and the agency now publishes a breakdown of clinical trial participants by sex, race and age subgroups.
Less than 16 percent of the world’s population is of European descent, yet other racial groups remains highly underrepresented in current genetic and medical research. Just three years ago, researchers found that 81 percent of genome wide association studies were of people of European descent. A study that same year examined tumor samples in the Cancer Genome Atlas repository and found seventy-seven percent of the samples were from whites, 12 percent from blacks, and 3 percent from Asians. Even more remarkably, a recent study of the African-American genome found that 10% of that genome is missing from the reference human genome that is the foundation of personalized medicine.
The genetic revolution in medicine has shown us that there is profound genetic variation in the human population. In order to fully exploit this seminal information and improve and personalize the outcome of medical treatments, the research enterprise must expand its efforts to incorporate this human diversity in its portfolio.