“Genomic medicine is opening new possibilities for clinical psychiatry. Through whole genome sequencing, we can better understand the genetic factors that contribute to mental illness, with the hope of providing personalised diagnosis and medication strategies to patients while reducing medication side effects.”
Dr Fong Chun-ho
Associate Consultant (Psychiatry), Kwai Chung Hospital
Awardee of the 2023/24 HKAM-HKGI
Research Excellence Grants in Genomic Medicine 2023/24
Mental Illness and the Genetic Connection
The causes of mental illness have long been an important area of medical research. As Dr Fong Chun-ho introduced, “The vast majority of mental illnesses relate to both genetic and environmental factors. These conditions are typically influenced by multiple genes rather than a single gene.”
Through genome-wide association study (GWAS), researchers have identified an increasing number of genetic variants associated with mental disorders. “For example, schizophrenia maybe connected to genes that affect the immune system and neurotransmission, while bipolar disorder is associated with genes that control how brain cells communicate. Understanding these genetic variants helps us predict disease mechanisms and enriches our knowledge of these conditions,” explained Dr Fong.
Genomic Breakthroughs in Psychiatric Diagnosis
The rapid development of genomic medicine in recent years has the potential to open new pathways for the diagnoses of mental disorders. “Genetic screening allows us to identify high-risk population before symptoms appear,” Dr Fong said. “We now know that chromosomal and genetic conditions such as Fragile X syndrome, Down syndrome, and DiGeorge syndrome are associated with increased risks of autism, Alzheimer’s disease, and schizophrenia respectively. These discoveries enable us to conduct disease screening, diagnoses, and treatments more efficiently.”
This is only the start of realising the potential of genomic medicine. Dr Fong added, “Leveraging advancements in medical technologies, scientists have already been assessing the combined impact of hundreds of genetic variants alongside environmental risk factors to develop screening models for mental illnesses. In time, the establishment of polygenic risk scores will enable more accurate prediction of risks of developing mental disorders, facilitating early intervention or even prevention.”
Personalised Medicine Becoming Reality
With its valuable insights into the genetic foundations of mental health disorders, genomic medicine is also driving new momentum in disease treatment and patient care. Pharmacogenomics, which studies how genes affect drug responses, has become an essential tool in transforming future psychiatric medication strategies, allowing doctors to predict both medication effectiveness and potential adverse reactions based on a patient’s genetic profile. Dr Fong explained, “For example, before prescribing the mood stabiliser Carbamazepine, we must conduct genetic screening for the HLA-B*1502 variant. Patients carrying this gene face high risks of developing severe, potentially fatal skin reactions like Stevens-Johnson syndrome when taking this medication, with symptoms including widespread skin peeling and tissue death.”
Dr Fong believes that as this new sphere of modern science and medicine continues to flourish, such approach of personalised medicine can be further expanded. The goal of pharmacological research in genomic medicine is to analyse patients’ genetic profiles to predict their responses to different psychiatric medications, thereby optimising treatment outcomes while minimising side effects. It is anticipated that in the near future, applications of genomic medicine will further enhance the precision of psychiatric treatments and inspire research and development of new drugs, bringing benefits to patients.
“Although mental illnesses are often associated with environmental and social factors such as childhood trauma and stress, and we still have much to learn about the relationship between genetics and mental health, genomic medicine holds tremendous promise,” Dr Fong concluded. “It will enable more effective diagnoses and treatments for psychiatric patients, ultimately enhancing their quality of life. This is the belief that drives me as a clinician and researcher.”
Genomics Research on Tardive Dyskinesia and Antipsychotic Medications
Dr Fong’s research focuses on tardive dyskinesia (TD) caused by antipsychotic medications. TD is a serious and often irreversible medication side effect affecting approximately 10% – 20% of antipsychotic drug users. Symptoms include uncontrolled movements of muscles in the mouth, tongue, or other body parts. The pathological mechanisms of this condition remain incompletely understood.
Dr Fong’s research explores the association between IL-10 genetic variations and the risk of developing TD. IL-10 is an important anti-inflammatory cytokine that helps regulate the immune and antioxidant systems. Through this research project, Dr Fong aims to examine three specific genetic variants of IL-10, and compare the differences between 160 patients and non-patients to gain a deeper understanding on the relationship between IL-10 and the mechanisms underlying TD.
For patients who need antipsychotic medications, tailored prescriptions could alleviate symptoms, reduce the risk of side effects, and enhance medication adherence, thereby improving their quality of life and facilitating progress towards recovery. This research is anticipated to deepen our understanding of applications of genomic medicine in mental health care, from predicting disease risk to enhancing diagnostic accuracy and ultimately enabling personalised treatment plans.