Basics of integrative psychiatry/functional medicine:

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So often, when people come to see me, they already have a sense of what DSM diagnosis they’re struggling with. Maybe a previous provider gave them a label, or maybe they did some reading and recognized that their symptoms align with a condition like depression, anxiety, OCD, or bipolar disorder. They’ve often tried treatment — sometimes many treatments — that are consistent with current medical guidelines. And yet… they’re still not getting better.

So what gives?

The DSM (Diagnostic and Statistical Manual of Mental Disorders) represents a huge leap forward compared to how mental health was understood 100 — or even 500 — years ago. It provides a shared language that helps clinicians identify and classify mental health conditions based on patterns of symptoms. But here’s the catch: each DSM diagnosis is just that — a description of symptoms. It doesn’t necessarily tell us why those symptoms are happening.

Historically, the thinking has gone something like this: if you have depression symptoms, maybe it’s a serotonin imbalance — so we try an SSRI. If you have symptoms of psychosis, maybe it’s excess dopamine — so we try a dopamine-blocking medication. And for many people, these treatments are helpful and even life-changing.

But what happens when they’re not?

What happens when someone has tried four different antidepressants that all increase serotonin, and none of them help? Or when someone continues to experience hallucinations or paranoia despite multiple antipsychotic medications?

As I like to say: if what you’re doing isn’t working, then what you’re doing isn’t working. It seems obvious, but it’s often overlooked in clinical care. If a person doesn’t improve after trying multiple medications within the same class — ones that target the same neurotransmitter — maybe we’re targeting the wrong system. Maybe there’s something else driving the symptoms that hasn’t yet been uncovered.

So what kinds of things might be at play when someone has been given the “right” diagnosis and followed the “right” treatment plan, but still isn’t getting better?

Broadly speaking, I divide root causes into two categories:

1. Conventional medical issues — These are things I learned about in medical school and are well-accepted within mainstream Western medicine as potential contributors to psychiatric symptoms. (Think: thyroid dysfunction, autoimmune conditions, certain infections, seizures, nutritional deficiencies, medication side effects, etc.)
2. Functional and systems-based contributors — This is a newer, more nuanced way of looking at the body and mind. Functional medicine explores how complex, interrelated systems (digestion, detoxification, immune regulation, mitochondrial function, hormone signaling, and more) affect how we feel. It also recognizes that symptoms like brain fog, chronic fatigue, and gut discomfort — which don’t always show up neatly on conventional labs — can still point to underlying biological disruptions.

These frameworks aren’t mutually exclusive — they complement one another. In fact, the best care often comes from combining the rigorous investigation of conventional medicine with the broader lens of functional medicine.

I’m far from the first clinician to notice the shortcomings of a purely symptom-based DSM approach. In fact, the National Institute of Mental Health created the Research Domain Criteria (RDoC) to push research beyond checklists and toward the underlying neuro-biological and behavioral circuits driving those checklists. RDoC organizes findings by domains such as Negative Valence (threat/fear), Cognitive Systems, and Arousal/Regulatory systems, treating them as dimensional traits that cut across traditional diagnoses. While RDoC isn’t ready for routine office use just yet, it’s a powerful proof-of-concept—and a reminder that we should always be looking “under the hood” rather than settling for label-based care.

One of the most straightforward places to begin — and often overlooked — is nutrition. Nutrients can be divided into:

• Macronutrients — These include carbohydrates, proteins, and fats, which serve as the body’s main fuel and building blocks. Deficiencies here may not always look like malnutrition, but imbalances (like too little protein or the wrong kinds of fats) can have real impacts on mood, energy, and focus.
• Micronutrients — These include vitamins, minerals, amino acids, and essential fatty acids — all of which play a role in neurotransmitter synthesis, mitochondrial function, detoxification, and immune regulation. Even mild deficiencies can contribute to psychiatric symptoms, especially when combined with genetic factors, inflammation, or gut absorption issues.

Ah, ferritin, the protein that stores iron in your body. Even when iron and hemoglobin levels are normal, ferritin can still be low — and when it drops below about 40 ng/mL, many people begin to experience fatigue, brain fog, hair shedding, or even restless legs. In my practice, I often aim for ferritin levels above 70 ng/mL, especially if a patient isn’t responding to standard depression treatments. I've actually had a patient on the inpatient who unit who developed life-threatening malignant catatonia - thought to be due to her ultra-low ferritin combined with her medication - even though other blood markers like iron and hemoglobin were normal! 

Similarly, B vitamins — especially B12 and folate — are absolutely essential for mental health. They play a key role in methylation, neurotransmitter synthesis, and cellular energy production. Some individuals have genetic variants (such as MTHFR or FUT2) that impair their ability to convert these vitamins into their active forms, even when blood levels look normal. Others may develop autoantibodies to cerebral folate receptors, which block folate from crossing the blood-brain barrier, leading to neurologic and psychiatric symptoms despite normal peripheral levels. And in some cases, patients may appear to have high B12 levels on labs — but what they actually have is macro-B12, a form bound to immune complexes that makes the vitamin biologically unavailable. That’s why I often check follow-up markers like methylmalonic acid (MMA) and homocysteine, which offer more sensitive insights into whether the body is truly getting what it needs. (For example, MMA goes up when B12 is functionally low, even if the B12 level itself looks fine.)

Another B vitamin worth mentioning is thiamine (vitamin B1). It was once thought to be deficient only in cases of extreme alcohol use or malnutrition, but we now understand that chronic stress, high-carbohydrate diets, and certain medications can all deplete thiamine — even in otherwise healthy people. A 2021 review in Biomolecules suggested that thiamine deficiency may be more common in Western populations than previously believed.

Then there are minerals like zinc and magnesium, which are essential for mental health but difficult to assess through standard lab tests. Because less than 1% of these minerals are in the bloodstream, serum levels often appear normal even when tissue levels are depleted. Clinically, we see signs like anxiety, muscle tension or twitching, poor wound healing (for zinc), or insomnia and migraines (for magnesium) that improve when we supplement — even if labs were technically in range. In these cases, how a patient feels may be a more useful data point than the lab number alone.

Modernity adds burdens our grandparents didn’t face. Ultra-processed foods crowd out nutrient-dense fare. At the same time, repeated low-dose exposure to environmental chemicals—glyphosate (Roundup) is a prime example—can raise oxidative-stress demands, deplete antioxidants, and impair gut absorption, all of which raise nutrient requirements. 

Carbs: You don’t have to meet criteria for diabetes to ride a blood-sugar roller-coaster. Highly refined, high-glycemic foods spike insulin, followed by a crash that can leave you foggy, irritable, or anxious. Studies link greater glycemic variability to lower quality of life and mood instability. 

Proteins: Neurotransmitters (serotonin, dopamine, GABA) are literally built from dietary amino acids. Adequate stomach acid is required to cleave protein into absorbable peptides. Aging, chronic stress, PPIs, or H. pylori can lower acid, leading to suboptimal amino-acid uptake even on a protein-rich diet. 

Cell-membrane “lipid rafts” made of cholesterol, phospholipids, and ceramides act as organizing hubs for receptors and signaling proteins. Emerging lipidomics shows that altered ceramide patterns correlate with mood disorders—particularly bipolar disorder—and may reflect mitochondrial distress or inflammation. Ensuring enough omega-3s (EPA/DHA) and minimizing industrial trans-fats can help nudge lipid-raft composition in a healthier direction.

Stay tuned...