In a first of its kind global research initiative, a team of scientists will analyse more than 94,000 brain scans from 257 research centres across 27 countries to investigate how eight mental health conditions affect brain function.
The five-year study will include participants aged four to 95 and examine serious mental illnesses, including schizophrenia, bipolar disorder, major depression, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder and anorexia nervosa.
The aim is to understand why different mental illnesses sometimes share similar symptoms while also identifying patterns that distinguish one condition from another.
For India, where mental health disorders affect millions and access to timely diagnosis and treatment remains a challenge, the findings could eventually open new avenues for research and more personalised care.
Led by researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of the University of Southern California, the five-year project is supported by a $3.2 million grant from the US National Institutes of Health (NIH).
According to the investigators, it will be the largest functional magnetic resonance imaging (fMRI) study of its kind, bringing together an unprecedented number of scans, research centres and psychiatric conditions under a common analytical framework.
“Each of these conditions has been studied mostly on its own, with each group using its own tools,” said Paul M. Thompson, associate director of the Stevens INI, director of the ENIGMA Consortium and principal investigator of the project.
“When every lab processes its scans the same way, we can finally discover which brain abnormalities are shared across disorders and which are specific. Our new global effort will have enormous power to identify brain signatures that are the most sensitive to each illness to help us target treatments and predict treatment response.”
Mental illnesses can affect mood, attention, memory, motivation, behaviour and a person's ability to function in everyday life. Some symptoms overlap, making diagnosis and treatment complex. However, the conditions are not interchangeable, and a symptom such as poor concentration or disturbed sleep can have several causes.
The new project aims to examine how different parts of the brain communicate and coordinate their activity, rather than looking at each disorder in isolation.
Researchers will use resting-state fMRI, a technique that measures changes in blood oxygen levels associated with brain activity while a person lies quietly in a scanner. When activity in two brain regions rises and falls in a coordinated way, researchers interpret this as a sign of functional connectivity.
These connections form networks involved in functions such as attention, planning and the regulation of thoughts and emotions. Studies have reported differences in these networks among people with psychiatric conditions, but findings have often been difficult to compare because research teams use different scanners, processing methods and analytical approaches.
Frank Hillary, professor of psychology and neurology at Pennsylvania State University, said many psychiatric conditions were believed to share some roots in brain biology, but research had largely developed along separate tracks.
“One critical goal of this project is to develop shared methods for studying how brain networks function so that different areas of psychiatry can be examined side by side to better understand their similarities and differences,” he said.
The project expands the work of the ENIGMA Consortium, an international network of more than 2,500 scientists across 47 countries studying the brain in health and disease.
Eight international research groups, each focused on one of the disorders, will use the same standardised processing pipeline — a common set of software procedures to clean the scans and measure connections and changes in brain activity.
This matters because an apparent difference between two studies may sometimes reflect how the scans were analysed rather than a genuine difference between the conditions. Applying a shared method should make it easier to identify patterns that can be compared across diagnoses, said the researchers.
They also plan to use artificial intelligence to examine the combined dataset. Large datasets can help AI systems detect subtle patterns that smaller studies may miss, although any resulting markers would need independent testing before they could be used in clinical practice.
The team will also investigate whether brain-function patterns reflect groupings suggested by earlier genetic research, including mood and psychotic disorders, developmental conditions and compulsive disorders. It will examine how medicines such as lithium and antipsychotics relate to differences in brain connectivity and activity.
Clara Moreau, assistant professor of psychiatry at the Université de Montréal and co-chair of the ENIGMA functional MRI working group, said the shared approach would help researchers compare findings across conditions more fairly.
“Agreeing on a targeted multiverse approach, which is used across the world and across disorders, lets us identify distinctive features of these conditions for the first time,” she said.
The need for better mental health research is particularly important in India, where the scale of the problem is substantial and many people do not receive timely care.
The National Mental Health Survey of India, conducted in 2015-16 by the National Institute of Mental Health and Neurosciences (NIMHANS), estimated that 10.6% of adults had a current mental disorder, while the lifetime prevalence was 13.7%. The survey also found treatment gaps ranging from 70% to 92%, depending on the condition.
The implications extend beyond the number of people affected. Untreated or inadequately treated mental illnesses majorly disrupt education, employment, relationships and family life. Families in many cases spend years trying to understand changes in a person's behaviour, arranging consultations and managing care, sometimes without access to specialist services nearby.
In conditions such as schizophrenia, symptoms can include hallucinations, delusions and difficulties with thinking or everyday functioning, while depression may affect mood, sleep, energy and concentration. Similarly, while bipolar disorder involves episodes of depression and mania or hypomania, autism and ADHD are neurodevelopmental conditions. OCD is characterised by intrusive thoughts and repetitive behaviours. Although there may be overlapping features, each condition requires its own careful assessment, said the experts.
