Global study pinpoints genes for depression across ethnicities
University of Edinburgh
New genetic risk factors for depression have been identified across all major global populations for the first time, allowing scientists to predict risk of depression regardless of ethnicity.
The world’s largest and most diverse genetic study ever into major depression has revealed nearly 300 previously unknown genetic links to the condition, experts say.
100 of the newly discovered genetic variations – small differences in the DNA sequence that makes up a gene – were identified due to the inclusion of people of African, East Asian, Hispanic and South Asian descent, the study found.
Previous research into the genetics of depression has focused primarily on white populations that originally descended from people living in Europe. Therapies developed using genetic approaches may therefore not be effective in other ethnicities, widening existing health inequalities.
Each single genetic variant has a very small effect on the overall risk of developing depression. If a person has multiple variants, these small effects can add up, increasing their risk.
The research team were able to more accurately predict an individual’s risk of depression by taking into account the newly identified variants.
The international team of scientists, led by the University of Edinburgh and King’s College London, looked at anonymised genetic data from more than five million people in 29 countries worldwide. One in four individuals included in the study were from non-European ancestries.
Researchers identified a total of 700 variations in the genetic code of individuals linked to the development of depression, almost half of which had never been associated with the condition before, implicating 308 specific genes.
The identified genetic variants were linked to neurons - a type of brain cell - across multiple brain regions, including areas which control emotion.
The findings offer new insight into depression’s impact on the brain and present possible new targets for treatment, experts say.
The research team highlight the existing drugs pregabalin and modafinil – used to treat chronic pain and the sleeping condition narcolepsy, respectively – which could potentially be repurposed for the treatment of depression, based on the study findings.
However, the team caution that further studies and clinical trials are needed to explore the potential of the drugs in patients with depression.
The study, funded by NIH, Wellcome and the National Institute for Health and Care Research Maudsley Biomedical Research Centre, is published in the journal Cell: https://www.cell.com/cell/fulltext/S0092-8674(24)01415-6 [URL will become active after embargo lifts].
The research team from the Psychiatric Genomics Consortium involved scientists from all continents, including studies from South Africa, Brazil, Mexico, the USA, Australia, Taiwan and China.
Professor Andrew McIntosh, study co-lead, from the University of Edinburgh’s Centre for Clinical Brain Sciences, said: “There are huge gaps in our understanding of clinical depression that limit opportunities to improve outcomes for those affected. Larger and more globally representative studies are vital to provide the insights needed to develop new and better therapies, and prevent illness in those at higher risk of developing the condition.”
Professor Cathryn Lewis, study co-lead, from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said: “Depression is a highly prevalent disorder and we still have a lot to learn about its biological underpinnings. Our study identifies hundreds of additional genetic variants that play a role in depression. These findings show depression is highly polygenic and open up downstream pathways to translate these findings into better care for people with depression.”
Journal
Cell
Article Title
Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell-types and pharmacotherapies
85% of Mexican Americans with dementia unaware of diagnosis, outpacing overall rate
Physicians may not be sharing the diagnosis promptly, if at all
More than three-quarters of older adults with dementia may be unaware of their diagnosis, a University of Michigan study finds.
That number is even higher — up to 85% — among Mexican Americans, who make up the largest share of the U.S. Hispanic and Latino population.
Fewer than 7% of all study participants, who live in Nueces County, Texas and were classified as having probable dementia based on a cognitive assessment, did not have a primary care provider.
The results are published in the Journal of General Internal Medicine.
“Dementia diagnosis unawareness is a public health issue that must be addressed,” said senior author Lewis Morgenstern, M.D., professor of neurology, neurosurgery and emergency medicine at University of Michigan Medical School and professor of epidemiology at the U-M School of Public Health.
“The diagnosis of dementia provides the opportunity to seek out treatment and home care services to help both patients and caregivers. If the diagnosis is not given, or the understanding of the diagnosis is unclear, it is a missed opportunity.”
Investigators found no link between access to primary care and awareness of dementia diagnosis. In other words, they weren't in the dark about their diagnosis for lack of communication with their doctor.
In fact, researchers suspect that the nature of patient-physician relationships is a central reason the awareness gap.
“The physician may not be diagnosing the patient or may be withholding the diagnosis of dementia,” said first author Josh Martins-Caulfield, a graduate of the U-M School of Public Health and medical student at the Icahn School of Medicine at Mount Sinai.
“In practice, physicians often hesitate to diagnose dementia, citing reasons such as insufficient time with individual patients to conduct the screening process or not having dementia-specific training. The discomfort of providing the diagnosis may also lead them to wait for patients or family members to raise concerns about memory issues rather than initiating discussions proactively.”
Several studies have found that the majority of older adults in the U.S. with probable dementia go either undiagnosed or are unaware of a diagnosis. One 2018 report revealed that Hispanic and Latino adults were more likely to be undiagnosed.
“Cultural competence is crucial in treating all patients, especially when dealing with a heavily stigmatized disease,” Morgenstern said.
Despite the lack of dementia awareness found in the study, having a formal diagnosis did not reduce a caregiver’s perceived burden.
This could be, researchers suggest, because the diagnosis forces caregivers to quickly confront the increased responsibilities that come with the diagnosis of dementia in a loved one, including decision making and managing daily care.
“Caregiving can be immensely taxing, particularly when balancing one’s own family responsibilities and personal life,” said Darin B. Zahuranec, M.D., M.S., co-author and a professor of neurology at U-M Medical School.
“Effective care necessitates accurate diagnosis combined with comprehensive emotional support and guidance for caregivers to access essential resources.”
Additional authors: Roshanak Mehdipanah, Ph.D., Emily M. Briceño, Ph.D., Wen Chang, M.S., Steven G. Heeringa, Ph.D., Kenneth M. Langa, M.D., Ph.D., Darin B. Zahuranec, M.D. and Nelda Garcia, all of University of Michigan, and Xavier F. Gonzales, Ph.D., of Texas A&M University, Corpus Christi.
Funding/disclosures: This study was funded by the National Institute of Neurological Disorders and Stroke (R01NS100687) and National Institute on Aging (R01AG069148), both of the National Institutes of Health.
Journal
Journal of General Internal Medicine
Article Title
Dementia diagnosis unawareness and caregiver burden in a multi-ethnic cohort
Article Publication Date
14-Jan-2025
COI Statement
This study was funded by the National Institute of Neurological Disorders and Stroke (R01NS100687) and National Institute on Aging (R01AG069148), both of the National Institutes of Health.
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