Medically reviewed by Fountain Chief Medical Officer, Doreen Zarfati, MD
Last reviewed: August 10, 2026

This article discusses emerging approaches in biological psychiatry and ketamine therapy. It is intended for educational purposes and does not replace individualized medical evaluation or treatment.

For a long time, psychiatry has been organized around symptoms.

Are you depressed?
Are you anxious?
Can you sleep?
Can you concentrate?
Do you have energy?
Are you functioning?

Oftentimes, these questions are difficult to answer. Anyone who has lived through a severe depressive episode knows that getting out of bed, sleeping through the night, concentrating at work, or feeling pleasure again can be a profound change. But there is another question that deserves equal attention:

What is happening underneath the symptoms, and what needs to change for recovery to last?

Depression, anxiety, cognitive problems, fatigue, sleep disruption, and emotional dysregulation do not exist independently of the body. They emerge from an interaction among the brain, immune system, metabolism, endocrine function, stress physiology, sleep, behavior, environment, and individual experience. Depression itself is now understood as a complex disorder with biological, psychological, and environmental contributors rather than a single underlying cause.

It doesn't mean that there's a blood test for depression. The meaning of the modern findings and research is that the brain exists within a biological system, and that system can increasingly be observed and measured.

We can measure metabolic and endocrine markers. We can examine inflammatory signaling. We can assess sleep and autonomic function. We can track symptoms and functioning over time. None of these measurements, taken alone, explains a person's mental health. But together with clinical history and careful observation, they can add information that a symptom questionnaire cannot provide by itself.

This is the emerging territory of precision psychiatry rooted in biology.

What We Have Observed at Fountain

The following observations are drawn from Fountain Health's clinical experience. They are not presented as research findings, population-level conclusions, or evidence that any particular intervention produces these outcomes.

In practice, we have observed that improvement in one dimension of mental health does not always mean that every other dimension has normalized at the same time. A patient may report meaningful improvement in mood while continuing to struggle with poor sleep, low physical activity, persistent stress, cognitive fatigue, or other factors that remain relevant to overall health. The observation is not that psychiatric treatment has failed. It is that recovery is multidimensional, and the different dimensions do not necessarily move at the same speed.

We have also observed that psychiatric care often evolves after the acute problem begins to improve. A person may initially seek treatment because of severe depression, anxiety, or another destabilizing condition, but once that immediate burden begins to recede, other questions become clinically important: How is the patient sleeping? Has cognitive function returned? Is energy improving? Is the person able to exercise, work, maintain relationships, and respond to ordinary stress? What factors might make another decline more likely? In that sense, the clinical problem can change even when the diagnosis has not.

Finally, we have observed that meaningful symptom relief can create something that was difficult to access during the worst part of an episode: capacity. A person who was previously unable to engage may become more capable of participating in psychotherapy, changing routines, exercising, reconnecting with other people, or addressing other aspects of health. We do not regard that period as proof of recovery. We regard it as an opportunity to build recovery, and then to determine whether the changes persist.

Ketamine offers an especially interesting example. Its rapid antidepressant effects have changed scientific thinking about how depression can be treated and have drawn attention to glutamatergic signaling, synaptic function, and neuroplasticity.

But ketamine may ultimately be important for a reason that extends beyond the drug itself. It raises a broader possibility:

What if some treatments are most valuable not simply because they relieve symptoms, but because they create an opportunity for the person to change? And if that opportunity exists, what should happen next?

I. Mental Health Is Biological: What We Can Measure, and What We Still Don't

The idea that mental health has a biological basis is hardly new. What has changed is how much of that biology we can investigate.

Depression is not one biological disorder. Two people can have nearly identical symptoms while arriving there through very different combinations of factors. One may be sleeping four hours a night while living under sustained stress. Another may have significant metabolic or endocrine issues. A third may have a history of trauma combined with social isolation and disrupted sleep. Another may have no obvious abnormality on routine laboratory testing at all.

The diagnosis may be the same in two patients, but there are different humans. That is one reason the old shorthand of a “chemical imbalance” is inadequate. The brain is not an isolated organ. It is part of an interconnected biological system.

The systems beneath mental health

Several biological systems are increasingly relevant to psychiatric research and clinical thinking.

Metabolic health affects cellular energy, glucose regulation, insulin sensitivity, and other processes relevant to brain function.

Inflammatory and immune signaling interacts continuously with the nervous system. Associations between inflammation and depression have been observed across many studies, although individual inflammatory markers are not sufficiently specific to diagnose depression or determine treatment on their own.

Stress physiology influences sleep, metabolism, immune function, cognition, and emotional regulation. Chronic psychological stress can become a physiological burden, while physiological disruption can make a person more vulnerable to psychological stress.

Hormonal systems influence mood, energy, cognition, and behavior. Thyroid, reproductive, adrenal, and other endocrine disturbances can also produce symptoms that overlap with psychiatric conditions, which is one reason a comprehensive medical evaluation matters.

Sleep and circadian biology affect mood and cognition directly. Poor sleep can be both a consequence of psychiatric illness and one of the factors that perpetuates it.

Autonomic regulation influences arousal, cardiovascular function, stress response, and recovery.

It's critical to understand that none of these amount to a checklist for diagnosing depression.

Biomarkers are signals, not answers

There is a temptation in the emerging field of biological psychiatry to assume that every measurable number must have an actionable meaning. We are not there.

A laboratory result outside a reference range does not necessarily explain a patient's symptoms. A result within the reference range does not establish that everything is biologically optimal. And an association between a biomarker and depression does not mean that changing that biomarker will necessarily improve the depression.

The useful question is more nuanced:

What does this information tell us about this particular person, in this particular context, and how does it change over time?

That shift, from isolated numbers to patterns and trajectories, is important. It is also where the distinction between conventional laboratory testing and a more comprehensive biological approach becomes meaningful.

The aim is not to turn psychiatry into a laboratory exercise. It is to give clinicians more information with which to understand the person sitting in front of them.

What We Have Observed at Fountain

The following are clinical observations from Fountain Health's practice. They are not presented as research findings or evidence of treatment efficacy.

1. Symptom improvement does not always mean that a patient's overall health has normalized.

In clinical practice, it is possible to see meaningful improvement in mood while other aspects of a patient's health remain unchanged. Sleep may still be poor. Physical activity may remain limited. Stress may remain high. The patient may still feel cognitively slowed or physically depleted.

The observation is not that psychiatric treatment has failed. It is that the dimensions of recovery do not necessarily move at the same speed.

2. Patients often remain in treatment long after the acute problem has changed.

A patient may enter care because of a severe depressive episode and later remain in treatment for reasons that are less obvious from a symptom score alone. The clinical picture evolves.

What began as crisis management may become questions about sleep, cognition, energy, relationships, stress, medication burden, physical health, or preventing another decline.

This has reinforced a simple idea in our practice: Psychiatric care should evolve as the patient's state evolves.

3. The period immediately after meaningful symptom relief can be clinically important.

When someone has been severely depressed, the first improvement can create something that was missing before: capacity.

Capacity to engage in therapy. Capacity to exercise. Capacity to reconnect with other people. Capacity to make changes that felt impossible during the worst part of an episode.

We view that period as an opportunity rather than proof that a patient has recovered. The question becomes what can be built during that opportunity and whether the changes persist.

II. Feeling Better Is Not the Same as Being Well

Symptom relief matters, but it is not the same thing as recovery. A patient can experience a substantial reduction in depressive symptoms while still sleeping poorly, remaining physically inactive, living under sustained stress, feeling socially disconnected, or carrying patterns that make another episode more likely.

That's not to say that the treatment did not work. It means that the symptom and the system producing or sustaining vulnerability are not always the same thing.

Medicine already understands this distinction in other areas. A medication can lower blood pressure without eliminating every factor contributing to hypertension.

A GLP-1 medication can produce substantial weight loss without resolving every determinant of long-term metabolic health.

An inhaler can relieve asthma symptoms without eliminating every environmental or physiological factor involved in the disease.

The treatment can work, and there can still be more work to do. Psychiatry should be no different.

From symptom relief to durable recovery

A useful way to think about psychiatric recovery is as a progression:

Symptom relief
Are the symptoms improving?

Functional recovery
Is the person sleeping, working, thinking, exercising, relating, and participating in life differently?

Broader biological health
Are relevant physiological factors moving in a healthier direction?

Durability
Does the improvement persist?

These are related but different questions.

A depression score can tell us something important. So can a laboratory result. So can a conversation with a patient about how they are functioning.

The challenge is to understand how these pieces fit together. That becomes especially important in conditions in which relapse is common. The goal should not simply be to ask whether the patient is better today. It should be to understand what changed, why it changed, and what might help preserve that change.

III. Ketamine and Neuroplasticity: When the Brain Becomes More Capable of Change

Ketamine provides an unusually interesting example of this idea. Ketamine is an NMDA receptor antagonist that influences the glutamate system. Its rapid antidepressant effects appear to involve downstream changes in synaptic signaling and processes related to neuroplasticity, the brain's capacity to modify connections and functional organization. That is one reason ketamine therapy has become an important area of research in treatment-resistant depression.

Clinical studies have demonstrated rapid antidepressant effects of intravenous ketamine in people who have not responded adequately to conventional treatments. Researchers are now studying not only who responds, but why some responses last longer than others and how the benefits can be sustained.

The concept of neuroplasticity is particularly interesting because it changes the way we think about the brain. The adult brain is not fixed. Neural circuits respond to experience, learning, environment, and intervention.

Preclinical research has provided evidence that ketamine can influence synaptic plasticity. Human studies have also identified changes in functional connectivity associated with treatment response.

But one distinction is critical: Plasticity is not the same as recovery.

A brain that is more capable of changing does not automatically determine the direction of that change. That is where context enters the picture.

If a person receives an intervention that creates a period of increased plasticity but continues to live with severe sleep deprivation, chronic stress, social isolation, or other destabilizing conditions, there is no guarantee that the opportunity will become durable recovery.

Likewise, it would be premature to claim that psychotherapy, exercise, sleep, or other interventions necessarily “capitalize on” ketamine-induced neuroplasticity in a specific, proven way. The clinical evidence for these combinations is still developing.

But the question is worth asking:

If the brain becomes more capable of change, what kind of change are we helping the patient make?

That is where ketamine becomes more than a medication story. It becomes a model for thinking about treatment.

IV. Ketamine Protocol Is Not a Treatment Protocol. It's a Protocol for a Treatment Window.

Ketamine should not be reduced to a number of infusions. Nor should it be presented as a standalone reset button. The medication is an intervention. The protocol is the structure around that intervention. Recovery is the larger process.

Ketamine can produce rapid symptom relief for some patients with treatment-resistant depression. But the duration of benefit varies, and strategies for maintaining improvement remain an active area of research. This is why we think about ketamine differently.

Before the window

The clinician needs to understand the patient. That means psychiatric history, medical history, medications, sleep, substance use, physical health, psychological context, and the factors that may be contributing to the current condition. Where appropriate, biological information can add another layer of context.

During the window

Treatment needs to be precise. Dose. Monitoring. Setting. All matter. The patient's experience matters. Ketamine is not simply a molecule entering the bloodstream. It is an intervention occurring within a particular person, at a particular moment in that person's life.

After the window

This may be where the larger opportunity lies. The patient may now have more capacity to engage with psychotherapy, establish better sleep, become physically active, reconnect socially, examine patterns of behavior, or address other contributors to poor health. The appropriate combination will differ from one person to another.

The principle is simpler: If a treatment creates an opportunity for change, the rest of care should help the patient make use of that opportunity.

This is why we do not think of ketamine as the entirety of a treatment protocol. It is one component of a larger therapeutic process. And that idea extends well beyond ketamine.

V. From Treatment to Recovery: A More Complete Model of Psychiatry

What would psychiatry look like if symptom reduction were treated as one measure of success rather than the definition of success?

It would not mean abandoning medication, psychotherapy, or replacing established psychiatric care with laboratory testing. It would mean putting these tools into a more complete model.

Instead of:

Identify symptoms → prescribe treatment → measure symptoms → repeat

we can begin to think in terms of:

Understand the individual → identify relevant factors → choose an intervention → create conditions for change → measure what changes → adjust over time.

An infographic illustrating a better model of mental health care rooted in biology

That is a more useful definition of precision psychiatry. It recognizes that the same diagnosis can arise from different combinations of factors. It recognizes that patients respond differently to the same intervention. And it recognizes that the patient's state changes over time.

A treatment that made sense six months ago may not make sense today. That is why longitudinal measurement matters. A single laboratory result is a snapshot. A symptom score is a snapshot.

Recovery is a trajectory.

The goal is to understand that trajectory well enough to make better decisions along the way.

The future may be less about finding one perfect treatment

Consider a patient with treatment-resistant depression. Ketamine may provide meaningful relief. That relief may make it possible to engage more fully in psychotherapy.

Better sleep may improve mood and cognition. Physical activity may improve energy and metabolic health. Addressing an underlying medical issue may remove another source of physiological strain. Reducing chronic stress may change another part of the picture. And continued clinical observation may tell us whether those improvements are actually holding.

No single intervention has to be “the cure.” Several interventions, sequenced appropriately, may change the trajectory. That is the difference between treating an episode and treating a person.

The Goal Is Not Simply to Feel Better. It Is to Stay Better.

Psychiatry has made enormous progress. We have effective medications. We have sophisticated psychotherapies. We have neuromodulation. We have ketamine and other emerging treatments. We have better ways to measure symptoms and functioning. But the next evolution of psychiatric care may require a broader set of questions.

Not only: Is the patient better?

But: What changed? Why did it change? What else is influencing the patient's recovery? What can we do to reinforce it?

And ultimately: Is it lasting?

Ketamine offers a compelling example because its effects may involve a period in which the brain becomes more capable of change. But the principle is larger than ketamine.

Mental health is biological. Recovery is multidimensional. And meaningful psychiatric care should account for both.

The future of psychiatry may not be about finding a better way to suppress symptoms. It may be about understanding the person more completely, identifying the factors that matter, creating opportunities for change, and following those changes long enough to know whether they endure.

Feeling better is important. Recovery is more.

And the goal of treatment should not simply be to help someone feel well today. It should be to help them build a state of health they can sustain.

References & Further Reading

National Institute of Mental Health. Depression. Overview of depression, including biological, psychological, and environmental contributors.
NIMH — Depression

Kang MJ, Hawken E, Vazquez GH. The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity. Frontiers in Psychiatry, 2022.
PubMed — Ketamine and Molecular Neuroplasticity

Monteggia LM, et al. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology, 2023.
PubMed — Ketamine and Rapid Antidepressant Action

Neural connectivity moderators and mechanisms of ketamine treatment among treatment-resistant depressed patients: a randomized controlled trial. Study examining ketamine-associated changes in neural connectivity and treatment response.
PubMed — Ketamine, Neural Connectivity and Treatment Response

Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses. Review of the evidence and limitations surrounding inflammatory biomarkers in psychiatric disorders.
PubMed — Inflammatory Biomarkers in Psychiatric Disorders

Efficacy of intravenous ketamine for treatment of chronic post-traumatic stress disorder: a randomized clinical trial. Randomized clinical trial examining intravenous ketamine in chronic PTSD.
PubMed — IV Ketamine for Chronic PTSD

Number needed to treat (NNT) for ketamine and esketamine in adults with treatment-resistant depression: A systematic review and meta-analysis. Review of clinical efficacy estimates for ketamine and esketamine in treatment-resistant depression.
PubMed — Ketamine/Esketamine NNT Meta-analysis

Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review. Review of the emerging evidence concerning ketamine combined with psychological interventions.
PubMed — Ketamine-Assisted Psychotherapy Systematic Review