When Functional-Medicine Tweaks Don’t Move the Needle...

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(Disclaimer: All of the information contained on Knox-Psych.com is for educational purposes only. Dr Knox is NOT able to verify the complete accuracy and applicability of the information contained in the sources provided. This information is NOT meant to (and cannot possibly) replace a complete and personalized medical evaluation performed by and treatment plan developed by a qualified healthcare provider. Dr Knox implores that the decision to make any medical or lifestyle changes be made in conjugation and with the guidance of YOUR own personal qualified healthcare provider.) 

Even the most thorough nutrition and gut-health work-ups sometimes miss neurological or immunological conditions that mimic—or magnify—common psychiatric symptoms. Here are several often-overlooked diagnoses worth discussing with your clinician.

Catatonia is a brain-based condition that can drastically affect how a person moves, speaks, and responds to the world around them. It’s often associated with psychiatric or medical illnesses, but it's not a mental illness in and of itself—it's a syndrome, meaning a recognizable pattern of symptoms that can appear in many different conditions.

Most people think of catatonia as someone becoming frozen and unresponsive—and that’s one version of it, called stuporous catatonia. In this state, a person might stop speaking entirely, hold the same position for hours, stare blankly, or resist even gentle attempts to move them. They might appear confused or fearful, but not communicate it. Unfortunately, because it’s not well understood, stuporous catatonia can be mistaken for severe depression, psychosis, or even just “noncompliance.”

But catatonia doesn’t always look slow or shut down. There’s another version called excited catatonia, and it’s often harder to recognize. These are the patients who seem extremely agitated—they may pace nonstop, talk in pressured or nonsensical ways, repeat others’ words, or become suddenly aggressive or fearful. From the outside, it can look like mania, psychosis, or even substance intoxication. What’s often missed is that the agitation isn’t goal-directed—it’s not driven by a mood or delusion, but by a kind of motor disinhibition. They often can’t stop themselves.

Because catatonia can look so different from one person to another, and because there’s no single lab test for it, it’s often missed altogether. But there’s a surprisingly simple way to test for it: a lorazepam (Ativan) challenge. Lorazepam is a fast-acting anti-anxiety medication, but in catatonia, a small dose can lead to a dramatic improvement within minutes to hours. If someone suddenly becomes calm, starts speaking, or regains voluntary movement, it’s a strong clue that catatonia is the culprit.

For patients who improve somewhat with lorazepam but don’t fully return to baseline, adding a medication like memantine (Namenda)—which modulates the brain’s glutamate signaling—can help bring about more sustained recovery. This approach, though not always front and center in psychiatry training, can be life-changing for patients who have been misdiagnosed or inadequately treated for years.

Landau-Kleffner Syndrome is a rare but important condition that can look a lot like autism or even trauma. It usually shows up in children between ages 3 and 8 who had previously been developing normally, especially with language. Then—sometimes gradually, sometimes suddenly—they begin to lose their ability to understand or use language, even though their hearing is normal. Parents might say their child "tuned out," stopped responding to their name, or suddenly began having tantrums or unusual behaviors.

Here’s the part that often gets missed: in LKS, these changes are caused by seizure activity in the brain, especially during sleep. But these aren’t the kind of seizures most people think of (like shaking or passing out). They’re electrical disruptions in the brain that can be completely invisible from the outside. The only way to detect them is by using an EEG, a test that records brain waves—preferably overnight, since the abnormal activity often happens during sleep.

Without this test, kids with LKS might be misdiagnosed with autism, behavioral disorders, or even defiance. But with the right diagnosis, treatment often includes anti-seizure medications or steroids, and some children can regain their language and improve dramatically.

Most people assume that if a child had a serious metabolic disorder, it would’ve been picked up at birth during routine newborn screening. But here’s the truth: while many inborn errors of metabolism are caught early, some don’t show up until later, and others aren’t included on standard screening panels at all.

These conditions are genetic and affect how the body processes certain nutrients, amino acids, or fats. When one of these systems is off, it can lead to a buildup of toxic substances or a shortage of key compounds the brain needs to function, causing symptoms like:

• Developmental delay
• Behavioral problems
• Fatigue
• Seizures
• Features of autism

The challenge is that many of these kids don’t look sick in a conventional way, so their symptoms are often chalked up to ADHD, anxiety, or just "quirky" behavior. But a comprehensive metabolic work-up—looking at blood and urine for specific patterns, such as amino acid levels, organic acids, or lactate/pyruvate—can reveal treatable issues.

A 2022 review paper highlighted that undiagnosed metabolic conditions are more common in neurodevelopmental disorders than many realize, and early detection can lead to dietary changes, supplements, or medications that dramatically improve outcomes.

Autoimmune encephalitis is a condition where the body’s immune system mistakenly attacks the brain. One specific type, anti-NMDA receptor encephalitis, gained public attention after being featured in the memoir and film Brain on Fire.

In adults or teens, it might start with sudden changes in behavior, like paranoia, hallucinations, memory problems, or mood swings. In children, it might look more like severe anxiety, sleep problems, or regression. Because the symptoms overlap so much with psychiatric conditions, these patients are often misdiagnosed with schizophrenia, bipolar disorder, or severe anxiety—when the real issue is inflammation in the brain.

Clues that raise suspicion include:

• Rapid onset of symptoms
• Movement abnormalities (like twitching or stiffness)
• New-onset seizures
• Fluctuating levels of consciousness

Diagnosis requires blood tests, brain imaging (MRI), EEG, and sometimes a spinal tap. The good news is that when correctly identified, autoimmune encephalitis is often very treatable—with immune-based therapies like steroids, IVIG, or plasma exchange.

If your child seemed fine one week and then suddenly developed severe OCD, food refusal, separation anxiety, or rage attacks out of nowhere, PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) or PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) could be worth considering.

These conditions happen when the immune system, in trying to fight off an infection (often strep throat), accidentally targets parts of the brain involved in emotion and movement. The result can be striking: a child who was previously calm and easygoing might suddenly become terrified of contamination, unable to eat, or aggressive.

There’s no single test that proves the diagnosis. Instead, it's made based on:

• A sudden, dramatic onset of symptoms
• Evidence of a recent infection
• Inflammatory markers in bloodwork
• Clinical judgment

Treatment may involve antibiotics, anti-inflammatories, or even immune-based therapies depending on severity. This area is still evolving, but more clinicians are recognizing it as a real and treatable form of brain-immune interaction.

Wilson’s disease is a genetic condition where the body can’t properly get rid of copper, leading it to accumulate in the liver, eyes, and brain. In teens or young adults, one of the earliest signs can actually be psychiatric symptoms—like irritability, depression, impulsivity, or personality changes—long before any physical signs appear.

Left untreated, the copper build-up can eventually cause:

• Liver damage
• Movement problems (like tremors or stiffness)
• Eye changes (called Kayser-Fleischer rings)

But if caught early, it can be managed with medications that help remove excess copper or block its absorption. A simple panel of labs—ceruloplasmin, 24-hour urinary copper, and an eye exam—can screen for it.

For individuals with severe psychotic symptoms that haven’t responded to other medications, clozapine is often considered the gold standard. It’s the only FDA-approved medication specifically indicated for treatment-resistant schizophrenia, but what makes clozapine especially interesting is that it does more than just block dopamine. Clozapine also appears to modulate the immune system and reduce inflammation, which may explain why it works so well in certain cases of psychosis where the exact cause is unclear—especially when there’s suspicion of underlying immune or inflammatory involvement.

Families exploring clozapine often feel isolated, since it’s a medication that requires close monitoring (like regular bloodwork), and it’s not commonly prescribed unless symptoms are severe. But there’s a wonderful support network called Team Daniel, started by parents of a young man who found life-saving improvement on clozapine. They host a Facebook group and a weekly Zoom call, where families, patients, and providers can share experiences, ask questions, and support each other through the journey. It’s a phenomenal community for anyone walking this path—and a reminder that healing often happens best when we’re connected.

Sometimes what looks like an eating disorder—especially in children or teens—is actually something deeper happening at the metabolic or genetic level. While conditions like anorexia nervosa are typically seen as psychiatric in origin, new research suggests that for a small subset of patients, there may be an underlying biological driver that affects how the body processes key nutrients or senses hunger and satiety.

Certain genetic variants (sometimes called mutations, but many families prefer the gentler term “variants”) can impact how nutrients like zinc, amino acids, or essential fatty acids are absorbed or utilized in the body. These variants can cause disruptions in brain signaling—especially in regions that regulate appetite, mood, and energy—which may show up as extreme food aversions, loss of appetite, rigid eating rituals, or intense restriction. In some cases, the person may appear to have an eating disorder, but the root cause is metabolic or neurogenetic.

Dr. Michael Lutter, a psychiatrist with a private practice here in DFW, has been a leading voice in this space. His research explores how rare genetic variants—particularly those affecting the brain’s response to energy balance and reward—can predispose people to restrictive eating behaviors.He’s also helped identify specific molecular pathways where nutrient signaling and psychiatric symptoms intersect. In some cases, identifying these variants has led to targeted nutritional or metabolic treatments that ease symptoms when traditional therapies alone weren’t enough.

This is a fast-evolving area of science, but it’s an important reminder: when a patient’s symptoms don’t fully fit the typical picture—or don’t respond to standard care—it may be worth asking whether their body is trying to tell a different story. And in some cases, genetic or metabolic testing can help decode it.