Mental Health Is Biological: Why Is That So Hard to Accept?

By Michael P. Milham, MD, PhD
Chief Science Officer, Child Mind Institute

For neuroscientists and mental-health professionals, it is not controversial that ADHD, autism, depression, PTSD, and related conditions have neurobiological roots. Decades of genetics, neurochemistry, and brain-imaging research confirm that neural circuitry and chemistry matter. The tricky part is that patterns are clear when we look at large groups, but much harder to spot in one person.

At the group level — when data from hundreds or thousands of people are analyzed — we detect reliable patterns confirming disruptions in brain function, suggesting that a brain pathway may run faster or slower, or that a cortical region is fractionally thinner. At the individual level, however, those same differences are often obscured by natural variation from one person’s brain to the next. It’s like knowing Steph Curry averages 24 points per game — you can detect a reliable pattern across many games—but it won’t tell you if he scored 10 or 50 on a particular night. Group-level brain findings work the same way: they show real, measurable effects, but they may not always be useful for pinpointing what’s going on in a single person at one point in time.

Consider asthma and air-quality research: we know airway inflammation underlies the condition, yet pollution, allergens, and stress govern who develops symptoms and when. There are no obvious lesions on a scan, and no single region lights up to explain everything. Mental health disorders are similar. We must hunt for multiple, subtle signatures — an endeavor that demands patience, sophisticated tools, large datasets, and replications. Fortunately, advances in high-resolution brain imaging, digital monitoring, machine-learning algorithms, and artificial intelligence are accelerating our ability to spot these subtle patterns. This is the modern face of the long-running “nature-versus-nurture” debate: biology provides the wiring, but experience fine-tunes how — and whether — those circuits spark when challenged.

Three key concepts from developmental science illustrate how biology and environment shape mental health across childhood and adolescence. This ongoing interaction between biology and experience is best understood through three complementary frameworks that scientists regard as cornerstones of developmental health — how brains and behaviors evolve from infancy through adulthood.

Differential susceptibility — sometimes called the “orchid-and-dandelion” model — shows that children differ in biological sensitivity to their surroundings. “Orchids” thrive spectacularly in nurturing conditions but can wither under stress; “dandelions” are less reactive, doing reasonably well in almost any soil.

Building on that idea of uneven sensitivity, the two-hit hypothesis explains how timing matters: a first “hit” (such as a genetic vulnerability or perinatal complication) may sit silently for years until a second “hit” (e.g., puberty, a head injury, sustained bullying) pushes the system past its tipping point and visible symptoms emerge.

Finally, stress-inoculation theory offers a hopeful counterbalance. It shows that brief, manageable challenges — speaking in front of a class, tackling a difficult project with support — can act like a training vaccine, fortifying the brain’s coping circuits for future adversity.

Together, these models clarify why the same life event can derail one child, barely register for another, and actually strengthen a third: Biology sets the reactivity dial, environment turns the knob, and timing shapes the final outcome.

The clinical categories outlined in the official Diagnostic and Statistical Manual — even though they often arise from meticulous bedside observation — do not map neatly onto separate neural circuits. As Tom Insel, former director of the National Institute of Mental Health, observed, “the brain didn’t read the DSM.” History shows that astute clinical clues can unlock biology: think of how Rett syndrome, Fragile X, or specific heart-rhythm patterns pointed researchers to the underlying genes and pathways. The challenge for psychiatry is similar, but the signals are subtler and more distributed. Moving from broad labels, like “ADHD” or “depression,” to precise brain-based subtypes will require not just patience but also innovation — richer, smarter, and more individualized brain imaging; real-time digital phenotyping; advanced analytics; and cross-disciplinary methods that can capture the brain’s complexity on an individual level.

Recognizing a brain basis for mental health disorders doesn’t erase the role of the environment. Brains are shaped by both genetics and life experience — by trauma and chronic stress, but also by stable communities, good nutrition, and supportive relationships. Biology and context continually interact, influencing not just whether someone develops symptoms, but how they cope, recover, or even grow.

• Conditions like ADHD, depression, and autism reflect real brain-based differences, and even subtle signs deserve attention.
• No single blood test or scan can diagnose these conditions today, but precision psychiatry is rapidly coming into focus.
• Continued research will clarify biomarkers and counter claims that we are “over-medicalizing” human behavior.

Sensational headlines that frame mental health as “over-medicalization” only serve to fuel confusion and stigma. Every stable difference in behavior rests on a biological substrate — even if that substrate is subtle and hard to detect in a single person.

When we say “Why Is That So Hard to Accept?” we’re issuing a wake-up call. Let’s anchor our understanding in the undeniable — if nuanced — reality that mental health and its disorders reside in the brain. Admitting complexity is not denying reality. With continued research and ever-improving tools, we can advance toward truly personalized, compassionate mental health care — free from buzzwords and grounded in biological truth.