A Meeting of Minds: How Singapore is Building a New Model for Mental Health Research

For the 1 in 7 Singaporeans who experience a mental health condition over the course of their lifetimes, these questions are anything but theoretical. “We need to remember that behind all these statistics are real individuals and real families that are struggling,” said Professor Patrick Tan, Executive Director of Precision Health Research, Singapore (PRECISE), speaking at the Gut Linked Outcomes in Wellbeing (GLOW) and University of Wisconsin–Madison (UW–Madison) symposium ↗ (opens in new tab) held on 22 May 2026.

In addition to the social stigma, which leads four in five ↗ (opens in new tab) Singaporeans with depression or anxiety to avoid seeking professional help, mental health is challenging to address because of its inherent complexity. “Diet, environment, life experiences, stress and social factors all play a role,” Tan explained, adding that emerging evidence also implicates the gut microbiome, trillions of microorganisms that colonise the digestive tract. By bringing together researchers from fields as diverse as epidemiology, psychiatry, genomics, microbiome science, data science and digital health, the GLOW UW–Madison partnership aims to not only come up with answers but to develop a new paradigm for mental health research.

The scale of the effort is considerable. The project builds on foundations already established through the PRECISE SG100K population cohort, which has assembled genomic and health data from more than 100,000 participants representing the country's diverse ancestral groups. Researchers aim to recruit more than 6,000 participants across Singapore and the United States. Participants will contribute stool and saliva samples, undergo psychological assessments, and share information about lifestyle and health behaviours. Many will also participate in digital phenotyping, allowing researchers to measure aspects of daily life through smartphone applications and wearable devices.

My microbes made me do it?

The rationale behind this interdisciplinary approach is a biological reality that challenges brain-centric psychiatry: the gut-brain axis. The gut and brain are so interconnected by a dense network of nerves and shared signalling molecules that the gut is sometimes called the second brain, said Professor Jo Handelsman, a lead collaborator from the University of Wisconsin-Madison and a former White House Office of Science and Technology Policy advisor. 

Mounting evidence points suggests that what happens in the gut can impact what is traditionally thought to be controlled by the brain, including Handelsman’s own research. In an ongoing study with collaborator Ryan Herringa, Handelsman found that when microbes from depressed adolescents were transferred to germ-free mice, the mice showed signs of depression including anhedonia and lowered persistence. “The idea that you could transfer a microbiome to a completely different mammalian species and see the kinds of changes that parallel human behaviour was pretty extraordinary,” Handelsman said. “It made me think that perhaps we are not fully in control of our moods or behaviours but are influenced by our microbes.”

Similarly, Handelsman’s other work on the Healthy Minds Program suggests that interventions such as meditation may alter both mood and microbial communities, hinting at complex feedback loops between behaviour and biology. Participants pre-screened for depression were assigned either to standard care or to an app-based intervention involving either a mini-lecture on awareness and purpose or the lecture and a guided meditation. The researchers found that after an average of five minutes of meditation a day for four weeks, about half of the participants showed a decrease in depression scores. 

Looking at their microbes, however, revealed another surprise. Even though those with the “lecture- only” and those who also meditated showed relatively similar scores on depression, they had dramatically different changes to their microbiomes. “There are some very specific genera that change in the community and we are very interested in the nature of those bacteria, what they may do for the human body, and how they affect mood,” Handelsman said.

Going global

GLOW, which brings together PRECISE, Duke-NUS Medical School, the Agency for Science, Technology and Research, the Genome Institute of Singapore, the Institute of Mental Health, NHG Health Polyclinicis, Tan Tock Seng Hospital, the Lee Kong Chian School of Medicine at Nanyang Technological University and the National University of Singapore, aims to test the idea that the gut microbiome can influence mental health at population scale, and then take things even further by comparing local findings with US data. GLOW is paired with a sister project in Wisconsin known as Lucida ↗ (opens in new tab). Together, the studies form the WisSing collaboration, creating comparable cohorts in two very different populations. For researchers, this presents a rare opportunity to distinguish universal biological mechanisms from factors shaped by culture, geography or ancestry.

Citing the example of how Europeans have a 1% risk of diabetes at a body mass index (BMI) of 30 while South Asians have the same risk at a much lower BMI of 20, Chief Scientific Officer of PRECISE, Professor John Chambers stressed the need to take this genetic diversity into account. “Unless you make international comparisons across ancestral groups, you will fail to appreciate what ‘healthy’ looks like in your own population,” he said.

“We want to be able to juxtapose what we find in Singapore against Western populations; this is not just representation for the sake of representation,” said Tan. “If we want global precision health to be successful, we need to understand what is unique among different populations, but also what is generalisable. Partnerships like WisSing are key, bringing together complementary strengths that are stronger than the sum of our parts."