Is epidemiology the key to predicting and intervening in mental disorders?

Professor Michael Meaney recently gave a series of lectures at Harvard University as part of the institution's Mind Brain Behavior Interfaculty Initiative (MBB). In the second of this two-part series, he shares how the adaptive nature of the human brain complicates our ability to identify predictive markers of common mental disorders and the role epidemiology plays in developing effective interventions.

Mental Health

There is a global crisis in mental health that existed long before the ravages of COVID-19. So where are we with respect to prevention and intervention? As a benchmark, over the last 50 years, clinical medicine has achieved a 75 percent decrease in the rate of premature death from heart disease. This remarkable achievement occurred as a function of a) the discovery of risk factors to identify the most vulnerable, b) definition of the processes that link risk to disease, c) interventions that target these processes to reduce risk, and d) personalising the intervention to the specific needs of the individual.

I fear that with respect to the most common forms of mental disorders, we are still in the starting blocks – unable to effectively identify high-risk individuals. This is frustrating because mental disorders are preventable. So why? One reason is that unlike heart disease, we haven’t much time. Common forms of mental illness show a peak age on onset over the peripubertal period and some, such as ADHD and anxiety, even earlier. Effective prevention requires assessment of risk in childhood and the identification of operative targets for intervention. My impression is that we continue to embrace perspectives suggesting that brain circuitry and function are crystalised in early childhood. And children do vary in social, emotional and cognitive function early in life.

But in the case of the most common mental disorders – including depression, anxiety and ADHD – these overt measures of brain function do not predict outcomes at the level of the individual?  There are certainly statistical associations between measures such as "temperament" in early childhood and later mental health outcomes. But the associations are generally weak and apparent only at the level of group analyses. Prediction at the level of the individual is poor.

Likewise, genome-wide association studies report significant associations, but account for only a small fraction of the variation in mental health status. The same can be said even for measures of environmental adversity. Poverty, harsh parenting and abuse in childhood all predict an increased risk for mental disorders, but with remarkable variability. Here as well, there is poor prediction at the level of the individual. 

The very nature of the highly plastic and adaptive brain – especially in youth – complicates our ability to identify predictive markers of common mental disorders. The transitions from family to school life and peer groups, puberty to emerging adulthood, all drive experience-dependent plasticity with the potential for considerable discontinuity from one stage to another. The normal transitional challenges of development drive the dynamic, plastic brain and will frustrate our search for predictive "markers" of risk for certain mental disorders at the level of the individual. 

But there is an alternative perspective. Our studies of child development employ the methods of epidemiology, which statistically associates measures of exposures or conditions with health status in populations. Epidemiology is the science of public health, not individual developmental trajectories. I suggest we can capture the existing knowledge for the sake of interventions at the level of the group rather than the individual. There are examples of "psychosocial" interventions targeting emotional (or self) regulation in classes of preschool children as an approach that is consistent with developmental science and they are effective. If common forms of mental disorders are a population health issue, perhaps we should consider a population health solution. 

(Adapted from Harvard University's MBB Distinguished Lecture)

Besides serving as Programme Director for the Translational Neuroscience programme at the Singapore Institute for Clinical Sciences (SICS), Professor Michael Meaney is also a James McGill Professor in the departments of Psychiatry and Neurology, and Neurosurgery at McGill University. Renowned for his research on stress, maternal care and gene expression, his scientific work focuses on epigenetics and the mechanisms by which adversity in early life might alter neural development and render certain individuals at risk of mental illnesses and/or learning disabilities later in life. One of the world’s most cited scientists, he has been invited to present his findings at research institutes, government health agencies, and scientific meetings globally. Through his work, he hopes to holistically depict what vulnerability to mental illnesses looks like, what constitutes resilience or risk, and what interventions can help stop these debilitating conditions before they take root in adolescence and early adulthood.

Harvard University's Mind Brain Behavior Interfaculty Initiative (MBB) was introduced in 1993 to encourage an interdisciplinary community of faculty from across the University to engage in research and other academic activities aimed at elucidating the structure, function, evolution, development, ageing, and pathology of the brain in the context of human behaviour, genetics, and society.