Genetic testing could greatly benefit patients with depression, save health system millions
A special kind of genetic test that helps determine the best antidepressant for patients with moderate-to-severe depression could generate substantive health system savings and greatly improve patient outcomes, according to new research from the University of British Columbia.
The study, published today in CMAJ, shows that in B.C. alone, implementing pharmacogenomic testing could save the provincial public health system an estimated $956 million over 20 years.
“Pharmacogenomic testing aims to match patients with medications that are more likely to be effective and cause less side effects, based on their genetic profile,” said co-senior author Dr. Stirling Bryan (he/him), professor at UBC’s school of population and public health, and senior scientist at Vancouver Coastal Health Research Institute (VCHRI). “Our findings show that the benefit to patients in B.C. could be enormous, including increased remission rates and better quality of life, while generating significant cost savings by keeping people out of hospitals and more intensive treatment pathways.”
One in 10 Canadians will experience major depression at some point in their lives, making it one of the largest public health burdens. While more than 35 antidepressant medications are available in Canada, over half of patients don’t respond to the antidepressant they are initially prescribed and roughly 27 per cent report adverse effects.
Previous studies have shown that up to 42 per cent of the variation in how patients respond to these medications is due to genetic factors. Pharmacogenomic testing uses genetic information, typically obtained using a cheek swab, blood test or saliva sample, to help guide medication selection and dosing.
“Genes play an important role in how our bodies metabolize different antidepressants, which ultimately influences their efficacy,” said co-senior author Dr. Jehannine Austin, professor of medical genetics and psychiatry at UBC. “The genetic insights provided by pharmacogenomic testing can help physicians make more informed treatment decisions and reduce the lengthy trial-and-error process that many patients experience in finding an effective medication.”
For the study, the researchers worked with patient partners, clinicians and health system and government partners to develop a simulation model that mimics the experience of patients with major depression, from diagnosis through to treatment, recurrence and recovery. By incorporating B.C. health administrative data, clinical trial data and defined treatment strategies, the model compared the projected journey of 194,149 adults with and without pharmacogenomic testing over a 20-year period.
The model showed that pharmacogenomic testing would result in 37 per cent fewer patients experiencing treatment-resistant depression, a situation in which the patients’ depression does not improve despite trying several kinds of treatment. Pharmacogenomic testing would also result in patients spending 15 per cent more time without depression symptoms, resulting in an anticipated 1,869 fewer deaths and 21,346 fewer hospital admissions over 20 years.
“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we are able to carefully simulate the treatment journey of people with major depression,” said first author Dr. Shahzad Ghanbarian, a mathematical modeler and health economist at the Centre for Clinical Epidemiology and Evaluation, a research group within the VCHRI and affiliated with UBC. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond B.C., where we might expect to see similar benefits, particularly within a comparable Canadian context.”
Linda Riches, who lives in Salmon Valley, B.C., has been living with major depression for over 30 years and was one of the patient partners who helped undertake the study.
“All people with major depression deserve to feel hopeful about their life. Genetic testing may give them the opportunity to know what treatment they need, not the 10 they didn’t need,” said Riches.
Pharmacogenomic tests are not currently offered through the public health systems across Canada, but patients can pay for them through private companies.
The researchers say their analysis makes a strong case for including pharmacogenomic testing as part of routine, publicly-funded health care for people with major depression in B.C., but more work is needed to determine how such testing could be put into practice.
“We’ve shown here this can be effective, and our next step is to figure out the best way to do it, with input from patients, physicians, government and health sector partners,” said Dr. Bryan. “Exploration of implementation strategies, such as which health-care professionals are best-suited to deliver pharmacogenomic testing, is the natural next step and remains unexplored in Canada.”
This study was funded by Genome BC, Genome Canada and Michael Smith Health Research BC.
Interview language(s): English
JOURNAL
Canadian Medical Association Journal
METHOD OF RESEARCH
Computational simulation/modeling
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Cost-effectiveness of pharmacogenomic-guided treatment for major depression
ARTICLE PUBLICATION DATE
14-Nov-2023
COI STATEMENT
Christian Schuetz reports research funding from Provincial Health Service Authority, Health Canada, Canadian Institutes of Health Research, Canadian Centre on Substance Use and Addiction (CCSA) and Clairvoyant; consulting fees from CCSA; and travel support from Suchtmedizin. He is chair of the addiction and psychosis committee of the International Society of Addiction Medicine; research lead, Mental Health and Addiction with the Provincial Health Service Authority; division head, Substance Use and Concurrent Disorders with the University of British Columbia; and sits on the scientific committee of the World Association on Dual Disorders. Jehannine Austin is vice president of the International Society for Psychiatric Genetics and associate editor with the Journal of Genetic Counseling. No other competing interests were declared.
Women with depression have 20% lower taurine concentration in the hippocampus
Precise observation using ultra-high magnetic field 7T MRI
Peer-Reviewed PublicationIMAGE:
(A) BRAIN REGIONS WHERE SPECTRA WERE MEASURED (YELLOW BOX) (B) 1H MR SPECTRUM IN THE HIPPOCAMPUS: HIPPOCAMPAL TAURINE SIGNAL SHOWN AT 3.4 PPM (ARROW). BLACK LINE: ACTUAL MEASURED SPECTRUM. RED LINE: LCMODEL FITTING SPECTRUM.
ABBREVIATION: TAU, TAURINE; CHO, CHOLINE; TCR, TOTAL CREATINE (CREATINE + PHOSPHOCREATINE); GLN, GLUTAMINE; GLU, GLUTAMATE; GLX, GLN+GLU; MLNS, MYO-INOSITOL, TNAA, TOTAL N-ACETYL ASPARTATE (N-ACETYL ASPARTATE + N-ACETYL ASPARTYL GLUTAMATE); MM, MACROMOLECULE.
view moreCREDIT: KOREA BASIC SCIENCE INSTITUTE (KBSI)
For the first time, a research team in Korea has discovered there is a significant relationship between depression and the taurine concentration in the hippocampus, an area of the brain responsible for memory and learning functions. This discovery provides the opportunity to publicize the role and importance of taurine in future prevention, diagnosis, and treatment of depression.
Using ultra-high magnetic field 7T human MRI (7T MRI), researchers (Drs. Youngkyu Song, Jee-Hyun Cho and Chaejoon Cheong) in the Korea Basic Science Institute (KBSI, President Seong-Kwang Yang) Biochemical Analysis Team have confirmed that the taurine concentration was significantly lower in the hippocampus of young females suffering from depression.
The study, conducted in collaboration with research teams led by Dr. Hyungjun Kim at the Korea Institute of Oriental Medicine (KIOM) and Prof. Jin-Hun Sohn at Chungnam National University (CNU), is the result of comparing two groups of female participants, a group of 36 female patients with major depressive disorder, and a control group of 40 healthy females. All participants were aged 19 to 29.
Depression is a disease that causes serious damage and loss, not only personally, but also socially and economically. According to the World Health Organization (WHO), there are more than 260 million people suffering from depression around the world, and more than 800,000 people take their own lives every year. In Korea, the increase in depression among young people is notable. Of the total 1,000,744 patients with depression, 185,942 individuals in their 20s accounted for the largest demographic, and the rate of increase has more than doubled in five years.
MRI is widely used in brain disease research as it can precisely scan specific locations in the body and obtain a variety of quantitative information. Previous MRI studies on depression have focused on revealing changes in metabolites mainly limited to the cerebral cortex area, at the edge of the brain. This study is the first to disclose the relationship between metabolites and depression in the hippocampus, located inside the brain.
To identify substances closely related to depression, the research team measured and compared concentrations of seven metabolites, taurine, choline, creatine, glutamine, glutamate, myo-inositol, and N-acetyl aspartate, present in the frontal, occipital, and hippocampus regions of young women.
When performing MRI scans, there are technical limitations in measuring metabolite concentration in the hippocampus due to its location in the brain. Also, it is particularly difficult to obtain a magnetic resonance spectroscopy (MRS) signal for taurine because it has a low concentration compared to other metabolites. Using 7T MRI, which achieves high signal sensitivity and resolution, and sLASER pulse sequence designed to reduce chemical shift displacement errors, the research team successfully measured the subtle differences in taurine signals in the hippocampus of the patient and control groups.
The concentrations of metabolites were also accurately measured with consideration to the precise distributions of the constituents, white matter, gray matter, and cerebrospinal fluid (CSF) which are dependent on the individual. In the future, it is expected these measurements will be applied to customized brain disease research, tailored to individual characteristics.
The leader of KBSI’s research team, Dr. Jee-Hyun Cho declared, “This study will promote research on the role of taurine in the hippocampus and its relationship with depression, and contribute to the pathogenesis research and diagnosis development of depression.” She added, “By using KBSI’s cutting-edge research equipment, we plan to conduct follow-up research on changes of taurine concentrations in the brain via long-term observation of depression patients, as well as the effect of taurine intake as a treatment for depression.”
The research team at KBSI proposed the initial research idea of the relationship between depression and taurine concentration in the hippocampus, conducted measurement of brain metabolites using 7T MRI, and carried out analysis of the resulting data. The KIOM and CNU research teams participated in recruiting depression patient and healthy control groups, conducted psychological tests and clinical interviews, and managed demographic information.
Taurine concentrations in the hippocampus, frontal cortex (anterior cingulate cortex, ACC) and occipital cortex (OCC) (red: depression patient group, blue: healthy control group). The average taurine concentration in the hippocampus is 0.91 mM for the depression patient group and 1.13 mM for the healthy control group.
CREDIT
Korea Basic Science Institute (KBSI)
The Korea Basic Science Institute (KBSI), a government-funded research institution established in 1988, conducts research and development, research support and joint research, related to high-tech research equipment as well as advanced analytical science technology. With the aid of cutting-edge research equipment and outstanding human resources infrastructure, KBSI aims to provide a global platform for domestic and international researchers to achieve creative and harmonious research outcomes.
This study was supported by the KBSI, KIOM, and National Research Foundation of Korea, and was published in the latest online edition of Biological Psychiatry, a renowned academic journal in the field of psychiatry.
JOURNAL
Biological Psychiatry
ARTICLE TITLE
Association between taurine level in the hippocampus and major depressive disorder in young women: a proton magnetic resonance spectroscopy study at 7 tesla
No comments:
Post a Comment