Vanessa Gourdine, PsyD, APN-C, IFMCP
Abstract
The incidence of mental health disorders increased by about 40% from 2019 to 2023. The incidence of mental health disorders continues to escalate while the outcomes remain poor. The outcomes of psychopharmacology are mildly to moderately effective and rarely, if ever, result in a cure. The expectation is a lifetime use of medication for symptomatic management. The following case is an example of an integrative mind-body approach that may lead to an actual cure of psychiatric conditions when focused on neuroinflammation and not solely on neurotransmitters. The current case involves a young man who had been hospitalized seven times within seven years and treated with multiple attempts at various combinations of polypharmacy, resulting in similar outcomes and more hospitalizations. He sought a functional medicine approach due to the poor outcomes with conventional treatment. Subsequently, he was admitted to our outpatient facility utilizing a multi-systems model of an in-depth mind-body assessment. The treatment was based on inflammatory markers likely triggered by multiple toxin exposures, aimed at eliminating the sources of inflammation and introducing lifestyle and diet modifications to support detoxification. The outcomes obtained were extraordinary, with a total remission of all symptoms up to and including a post-treatment two-year follow-up assessment. This suggests that our approach to creating health outcomes needs to be personalized and integrative of both mind and body to achieve the best outcomes. The case presents an alternative approach to conventional treatment involving polypharmacy and psychiatric hospitalizations.
Keywords
Functional Medicine, Schizophrenia, Complement C4, Neuroinflammation Depression, Case Report
Vanessa Gourdine, PsyD, APN-C, IFMCP; The Functional Medicine Centers for Personalized Care, LLC; Paramus, New Jersey, United States.
Corresponding author: Vanessa Gourdine, PsyD, APN-C, IFMCP
E-mail: [email protected]
Introduction
The incidence of mental health disorders rose 40% from 2019 to 2023.1 The outcomes for psychotherapies and pharmacotherapies remain poor.2 Current treatments of psychiatric disorders remain focused on neurotransmitters and ignore any other potential causes of changes in brain function. Much research is based on the theory that the blood-brain barrier (BBB) is largely impenetrable; however, there is evidence to the contrary, especially for inflammatory immune cells.3 Consequently, if inflammatory cells can enter the brain, then what are the effects? The research on the effects of neuroinflammation and the result of such inflammation point to the association with psychiatric symptoms of depression, schizophrenia, bipolar disorder, and others.4-6 Researchers also suggest that dietary habits can significantly influence inflammation, having a positive effect on both the body and brain. Several studies describe the positive influence of a diet consisting of anti-inflammatory foods on depression.7,8
There are connections between the microbiome and the brain. There are microbes in the gut that trigger inflammation, and that inflammation can become chronic. Chronic inflammation is known to cause changes in the brain, and these changes are linked to psychiatric diagnoses. Dysbiosis is defined as an imbalance of the commensal bacteria that are essential for the healthy production of neurotransmitters, as well as the barrier between the gut and the gut-brain axis. The gut bacteria, such as Escherichia, Enterococcus, and Streptococcus, are serotonin-producing microbes. Bifidobacterium and Lactobacillus are GABA-producing (gamma-aminobutyric acid), while Bacillus and Serratia are dopamine producers from the amino acids that synthesize their respective hormones and neurotransmitters in the microbiome. These are examples of microbes in the gut that comprise the microbiome. When there are imbalances in the population of these respective commensal bacteria, the condition is referred to as dysbiosis of the microbiome. Dysbiosis leads to systemic changes in the various pathways alluded to above.9,10
There are many sources of inflammation. A common source is the diet. Foods high in sugar content, as well as ultra-processed foods containing various chemicals, such as emulsifiers, can lead to higher levels of inflammation. The environment is another major source of inflammatory chemicals, such as pesticides, BPA (bisphenol A) from plastics, PFAS (polyfluoroalkyl substances), and glyphosate, which is an endocrine disruptor. These are only a few examples of the various toxins in our environment to which we are exposed daily.
Thus, a personalized food plan is not only an essential part of the intervention to limit the sources of inflammation but also to decrease inflammation by providing foods known to have high anti-oxidant properties.
The first step is to test and identify the specific toxins, given that testing vast numbers of toxins can be challenging. The treatment intervention is based on the identified toxins, followed by the detoxification process. The sources of inflammation can be the gut’s microbiome,2,3,9 or other organs.11,12 The intervention is based on examining the effects of inflammation. The impact of various toxins on different parts of the brain and neurochemistry varies widely. This may help explain the variability of symptoms for the same diagnosis and the variability in results upon using the same medications for the same diagnosis.
This study discusses the adoption of an integrative mind-body approach to treat psychiatric conditions, focusing on neuroinflammation and not solely on neurotransmitters. The treatment in this case study began with a focus on dietary sources of inflammation. An anti-inflammatory diet with support for detoxification pathways can lead to substantial improvement in the symptoms associated with schizophrenia and depression.
Initial Assessment
The patient was 37 years old at the time he presented to the practice for treatment and had stopped all medications due to a lack of benefit and side effects commonly associated with psychiatric medicines. He presented with a multitude of symptoms and a very long history of psychiatric hospitalizations and medications that began at the age of 30. He reported that he had been diagnosed with Schizophrenia, Bipolar Disorder II, and Major Depression, and had been admitted to psychiatric hospitals seven times in seven years, before his admission to this practice. He stated that he had no mental health issues before age 30. He was arrested for a violent crime he did not commit in his early 20s and was exonerated. Despite experiencing the trauma of the arrest and the trial, he denied having any specific mental health issues or post-traumatic stress disorder (PTSD) symptoms from the arrest. He stated that he started painting for a living soon after.
His occupation as a painter involved daily exposure to different chemicals. As reported, he did not use protective gear while working. Based on his report of exposure to toxins during his 20s and a report of developing psychiatric symptoms in his 30s, the symptoms were severe and repetitive despite ongoing conventional interventions with anti-psychotic and anti-depressant medications.
The patient described symptoms consistent with a thought disorder, a common symptom of schizophrenia. He would lose track of his thoughts. He struggled with focus and concentration while performing ordinary tasks.
In addition to the symptoms consistent with schizophrenia, he had physical symptoms that were consistent with inflammation. He reported difficulty falling asleep, a symptom associated with changes in brain chemistry, interfering with his ability to relax and produce the neurochemistry consistent with sound sleep.
He reported muscle and joint pain along with spasms and stiffness. He believed he had multiple food intolerances based on his experience of gastrointestinal discomfort from lactose, gluten, eggs, and yeast.
He had chronic sinusitis. He described hair loss and chronic fatigue. The clinical picture was consistent with inflammation, and the symptoms were overlooked when classifying a patient as schizophrenic. If the symptoms did not fit the diagnosis of schizophrenia, they were usually overlooked, and therefore not considered in the overall presentation that would press the need for an in-depth insight into the root causes. At the core of the Functional Medicine process, by definition, is to do a deep dive analysis of the root causes.
Medical, Family, and Psychosocial History
He reported his medical history of multiple hospitalizations, totaling 7 psychiatric admissions. He had an MRI of the spine following a car accident, and there were no abnormalities. A CT scan of the brain performed several years before admission to this practice revealed negative findings. Traditional medical tests did not find any underlying causes for his symptoms.
He underwent various medical evaluations before admission to the practice, which revealed negative findings. He had a tonsillectomy as a very young child. In December 2021, he tested positive for COVID-19 and treated himself with vitamins and fasting. He stated that his COVID-19 symptoms were headaches and confusion.
His family history included a father with multiple food sensitivities, celiac disease, eczema, asthma, and cancer. He reported that his sister was diagnosed with major depression and bipolar disorder, inflammatory bowel disease (IBD), and food allergies. The extended family history was reportedly positive for autoimmune diseases, cancer, and psychiatric disorders. Neither parent has a diagnosed psychiatric disorder. Both sets of grandparents lived until their late 80s and 90s and were not diagnosed with psychiatric disorders.
Prior Interventions and Outcomes
He was treated with different psychotropic medications. They were combined at times, and he reported he struggled to recall all the medications. He recalled the more recent ones: Zyprexa, Abilify, Risperidone, Olanzapine, and Haldol. He stated that medications created “terrible side effects” and that he could not tolerate most medications.
The outcomes of using multiple medications and changing dosages were described by the patient as not helping his condition. The side effects from the many medications at times made him feel worse, resulting in more hospitalizations, with the outcome of combining a different set of medicines. The result was an ongoing and repetitive cycle of the same ineffective outcomes with polypharmacy and hospitalizations.
Clinical Findings
He was exposed to multiple chemicals in his occupation. He described that the paints used were usually oil-based with xylene. He did not wear a mask or gloves while working for a decade with these toxic exposures. He reported having mold in his home, and based on the mold toxin report from the labs listed below, there were clear indications of chronic exposure.
His height and weight were 5’11”, 170 lbs, and his waist circumference was 37 inches. Blood pressure was 124/72. He did not not drink alcohol or use recreational drugs. He made attempts to exercise several times per week with aerobics and strength building, but stated that experiences of soreness and inflammation curtailed the frequency. On a scale of 1-10, he rated his psychosocial stressors as 7 for work and health, and below 5 for all other aspects of family, social life, and finances.
He reported practicing meditation, breathing, and prayer for supportive calming activities. He stated he has difficulty falling asleep and usually sleeps between 6 to 7 hours. He mentioned that he never feels rested or energized. He reported a low tolerance for other identifiable toxins, such as processed foods, cigarette smoke, perfumes, industrial chemicals, and pesticides, in particular. He stated that over the years, he has been exposed to glyphosate in non-organic foods and xylene in his occupation as a painter.
The Functional Medicine approach requires an in-depth assessment of various systems using the Matrix, which includes the antecedents, triggers, and mediators. Exercise, nutrition, stress levels, sleep, and relationships, along with the physiological and clinical imbalances listed below, are part of the Functional Medicine Matrix, which was the model used to assess the patient’s functioning. The identified disrupted systems in the matrix for this patient culminated in a series of complex symptoms that ultimately impacted the brain and mental functioning.
It is rare to have a case of a physical malady that is not accompanied by mental symptoms and vice versa. The Functional Medicine approach requires a focus on systems with an eye towards core causes. In this case, it began with assessing exposure to possible toxins disrupting the functioning of various metabolic systems.
The Functional Medicine assessments of clinical imbalances in the matrix are listed below. The descriptions of clinical imbalances are based on the major systems within the brain and body. By reviewing the symptoms and linking them to the physiological processes, the analysis guides the practitioner in creating a holistic picture encompassing the symptoms and the interacting metabolic processes associated.
Clinical and Physiological Imbalances
Assimilation, Respiration, Digestion, and Microbiome. Symptoms were consistent with assimilation issues, such as an imbalanced microbiome, adding to overall poor metabolic balance. The patient reported signs of food intolerance, leading to digestive problems. There were no signs of respiratory symptoms.
Defense and Repair. There were signs of systemic inflammation, such as bloating, indigestion, fatigue upon exertion, and joint and muscle pain.
Structural, Musculoskeletal, and Cell Integrity: He reportedly experienced musculoskeletal stress with spasms and pain.
Communication, Endocrine, and Neurotransmitters. He had signs of imbalanced hormones and neurotransmitters, as indicated by brain chemistry-related issues, with reports of psychosis. There were neuroendocrine imbalances as indicated by sleep issues, hair loss, concerns about cognition, and reports of difficulty sustaining focus and persistent brain fog.
Transport, Cardiovascular, Heme, Lymph. There were no signs of poor transport.
Biotransformation, Elimination, Bowel, Kidney, Methylation, and Cell Matter Waste. There were probable methylation issues. Given dysbiosis and the inability to tolerate a variety of foods that assist with the production of essential nutrients, there were likely issues with biotransformation.
Energy, Mitochondrial Functioning, and Nutrient Formation of ATP (Adenosine Triphosphate). There was a likely buildup of toxins caused by poor detoxification. Toxins impact mitochondrial functioning, culminating in lower ATP production. Consequently, this reduces the energy supplied to all cells, causing fatigue and chronic daytime sleepiness.
Lifestyle Factors: Sleep, Relaxation, Exercise, Nutrition, Stress, and Relationships. He practiced some relaxation and careful nutritional choices by occasionally eliminating a few intolerant foods such as sugar and gluten. He exercised occasionally.
Mental, Emotional, and Spiritual. He reported good spiritual practices with meditation and prayer.
Diagnostic Assessment
The assessment began with a discussion of the toxins causing inflammation and oxidative stress. In this case, the environmental sources were several, including the exposure to oil-based paints daily, mold in the home, and non-organic and processed food sources. He was exposed to multiple chemicals in his occupation, including the use of oil-based paints and the chemicals used in the paint. He reported that paint includes at least one known chemical toxin, xylene. He did not wear a mask or gloves while working for at least a decade with these toxic exposures.
Based on his report of symptoms, it was decided to test for markers of inflammation, environmental toxins, and gut microbiome. Lab tests for IgG mold toxins were included in the standard tests, along with C4a, a marker for inflammation associated with inflammatory responses to infections, autoimmune disorders, chronic fatigue, and/or tissue injury. The Biome FX test was administered to assess the status of the microbiome, a major contributor to inflammatory conditions and communication along the gut-brain axis (Tables 1 and 2).
Table 1. Timeline of Patient Diagnosed with Schizophrenia: Symptoms of Auditory Hallucinations, Thought Disorder, 7 Hospitalizations in 7 Years, Mixed Psychiatric Polypharmacy with No Resolution
| Date | Assessment Findings | Diagnostic Tests | Test Results | Therapeutic Interventions |
| 6-2022
Time of Admission |
Mind-body assessment with a history of multiple hospitalizations; no relief from medications. Symptoms of hallucinations, thought disorder, feeling unwell, poor sleep | Prior Lab tests and hospitalizations yielded no significant results according to patient reports. He requested an MTHFR gene test. The Medical Symptom Questionnaire (MSQ) is 62. | At the time of admission, the patient reported that general physical examinations yielded no significant findings in prior test results or PCP visits. | Before arriving at this practice, there were various medications of Haldol, Abilify, Zyprexa, Risperdal, Olanzapine, and others that he could not recall. He had Self-prescribed Niacin, zinc, Omega 3, Vitamin C, Saw Palmetto, L-Arginine, and NAC. |
| 7-2022 | Symptoms are still present from the time of admission to this practice. | Standard labs, CBC, CMP, Biome FX, Great Plains OAT (organic acid test) ordered to identify the presence of inflammation and toxins; Cyrex tests for BBB, pathogens, and autoimmune. MTHFR genetic single-nucleotide polymorphism (SNP).
|
CBC, CMP negative, C4a elevated 4541, OAT test found elevated arabinose, oxalic acid indicating Aspergillus, Candida and Penicillium toxins. His elevated Pyroglutamic acid was a sign of glutathione depletion and dysbiosis. Cyrex tests for pathogen and BBB were negative, but positive for autoimmune intrinsic factor. Lab results indicated toxins from mold and high levels of inflammation. He was positive for IgG to Candida, IgE to wheat, soy, and peanuts. OAT for catecholamines were positive with high levels of HVA/VMA ratio. MTHFR negative. Elevated B vitamins Nicotinamide 640, Nicotinic acid 8 and B12 1791. | The initial plan was designed to eliminate toxin exposure and IgE and IgG foods, to lower inflammation (see plan in table below). |
| An antioxidant diet is personalized based on food choices and the elimination of food intolerances and food allergies. | ||||
| 9-2022 | Initial post-treatment follow-up indicated mild improvement across all symptoms that were present at the time of admission. | Clinical Interview consisted of an assessment of food diary, the report of symptoms, and MSE (mental status exam). | Follow up with patient regarding compliance with the personalized food plan indicated moderate compliance with occasional use of intolerant foods, based on the review of his food diary. | See The Prescribed Plan NAC, L-Glutathione, Glucomannan, Chlorella, L. plantarum C88, Magnesium, L-Theanine, GABA, Methylated B vitamins, CoQ10, S Boulardii and Nystatin |
| 11-2022 | Significant improvement in mental health and physical health. | Assessment based on clinical interview and rating scale of symptoms. Health counseling provided. | Clinical assessment indicated very good adherence to the plan. | Continue with plan |
| Lifestyle changes include change of career; daily exercise; good adherence to anti-oxidant diet and supplements | ||||
| 2-2023
|
Sustained improvement in symptoms and overall health | Repeat of standard labs to assess overall health and inflammation. | Standard labs of CBC, CMP were all negative. C4a was down from 4546 to 917, and Candida from 0.71 to 0.59. | Continue with the plan as prescribed. Nystatin prescription was terminated. |
| 12-2023 | He reported feeling well for the first time in a long time. A normal sleep pattern is described. | Repeat of standard labs to assess inflammation markers. MSE, clinical interview, and rating scale reviewed. | Results were all within normal limits. Candida results went lower from 0.59 to 0.21 | Supplements were discontinued except for D3, B complex, and CoQ10. Magnesium, L-Theanine, and GABA were continued if desired. |
| 2-2024 | Reports continued good mental and physical health. | Clinical interview and rating scale completed. Standard labs repeated | MSQ 34; catecholamines and VMA are within normal limits for neurotransmitters. | He continued with lifestyle changes and food plan: avoid toxins, eat organic, and continue with exercise.
Continued with Vitamin D3, B complex 2-3× per week, and daily CoQ10. |
| 6-2024 Telemedicine follow-up at two years after treatment ended, with good results ongoing. No medications, no psychiatric symptoms, no hospitalizations. MSQ was a 6 down from the prior score of 34. | ||||
Abbreviations: ATP, Adenosine Triphosphate; BBB, Blood-Brain Barrier; C4a, Complement Component 4a; CBC, Complete Blood Count; CMP, Comprehensive Metabolic Panel; CNS, Central Nervous System; GABA, Gamma Amino Butyric Acid; HVA/VMA, Homovanillic Acid and Vanillylmandelic Acid; MSE, Mental Status Exam; MSQ, Medical Symptom Questionnaire; MTHFR, Methylenetetrahydrofolate reductase; NAC, N-Acetyl Cysteine; OAT, Organic Acid Test; SNP, Single Nucleotide Polymorphism
Table 2. Reference Ranges for Various Labs: The Results are Pre-Treatment and Patient’s Results are in Parentheses
| Reference ranges for positive lab results for Labcorp and the subject’s results are listed in parentheses. | C4a 0.0-650 ng/mL (4541 ng/ml) | IgE <0.10 KU/L Candida albicans (0.71-0.59-0.21), wheat (0.59), peanut (2.44), and soybean (0.44) | IgG food intolerances 0.0-1.9 ug/ml (multiple food intolerances all above 4.0 were eliminated) |
| Great Plains Reference ranges are mmol/mol creatinine | 3-Methylglutaric 0.02-0.38 (0.68), Arabinose <20 (32), 3-Oxoglutaric <11 (28), HPHPA <102 (119), Hydroxyphenalacetic 0.03-0.47 (0.74), HVA/VMA Ratio 0.32-1.4 (2.4), Vitamin B5 <5.4 (12) | Pyroglutamic 5.7-25 (33), 2-Hydroxybutyric <1.2 (2.6) | Orotic <0.46 (0.84), 2-Hydroxyhippuric <0.86 (0.89) |
| Reference Ranges for Biome FX | Microbiome Index 30-40 (27.45), Resistome 8-10 (7.3), Diversity Alpha/Beta 8-10 (5.71) (4.83) | ||
| Cyrex uses the ELISA Index, and results are in standard deviations | Intrinsic Factor 0.0-2.5 (>3.70) |
He completed routine labs on 7/26/2022, and his CBC and CMP were normal. The thyroid was normal. Vitamin D was low normal at 40. Lyme and ANA were negative. He had elevated B vitamins, believing that he had a methylenetetrahydrofolate reductase or MTHFR SNP, as he was supplementing regularly with B vitamins (Rugby brand 500mg of Niacin and a methylated B complex from Pure Encapsulations) for about 8 months. The results of the MTHFR test were negative, showing no active SNPs for these genes. Wheat allergy was positive. C4a was elevated at 4541 ng/ml with a reference range of 152.0-1559.4 ng/ml.
The following labs were chosen to elucidate inflammation, infections, dysbiosis, and sources of toxins. There were positive findings across the categories except for infections.
The results of the Great Plains Laboratory Organic Acids testi indicated that he has high levels of 3-Oxoglutaric and Arabinose at 0.8 and 32, respectively. Both indicate high levels of yeast overgrowth with a likely impact on the gut microbiome. Elevations of 3-Oxoglutaric acid indicated not only yeast overgrowth but may be due to metal and/or ammonia toxicity, causing disruptions in the Krebs Cycle. The result of 2-hydroxyphenylacetic acid at 119 was additional evidence of dysbiosis. High levels of HPHPA or (3-(3-hydroxyphenyl)-3-hydroxypropionic acid) are present when byproducts of Clostridium bacteria combine with typical metabolites. The presence of this molecule will result in high levels of dopamine metabolite of HVA, which he had at 2.2, exceeding the normal range, thereby creating an imbalance in the ratio of HVA/VMA at 2.4, with an upper limit of 1.4. This imbalance in the ratio is associated with behavioral and gastrointestinal symptoms, including depression, autism, schizophrenia, aggression, seizures, OCD, and hyperactivity.
He had high levels of Oxalic acid at 118, which was likely the cause of joint and muscle pain. He had high levels of 3-methylglutaric acid, which is a mitochondrial marker that may indicate mitochondrial dysfunction. Great Plains Laboratory reports that a symptom of methylglutaric acid elevation is muscle spasms, as the patient reported having spasms. A resource for interpreting the Organic Acid test is listed in the footnotes under Mosaic Diagnostics, a laboratory that purchased Great Plains in 2023.
The conclusive findings were markers were markers showing a need for detoxification. He had elevations across all markers for pyroglutamic acid, indicative of glutathione depletion at 33, with an upper limit of 25; a toxic exposure with elevations at 2.6, with a normal range below 1.2 for 2-hydroxybutyric acid, indicating the likelihood of toxic exposure and glutathione depletion in an attempt to detox. The elevation changes were most likely caused by his attempts to detox. Orotic acid is a sign of ammonia excess at 0.84, with normal levels below 0.46. The elevations of GI bacteria at 2-hydroxyhippuric acid are indicative of poor detoxification attempts. The elevations are likely caused by environmental toxins and molds, exacerbated by dysbiosis, and are the core causes for inflammation.
He completed the Biome FXii (see the link to the interpretation guide in the footnote). It indicated and confirmed the dysbiosis (with 27.45, while 40 is considered the healthy index, according to the reference provided by Biome FX). His diversity was low for both alpha and beta, which refers to the diversity of commensal bacteria. His resistome occurrence index was at 7.3 (10 indicates healthy). The keystone species were low across the board. He had low out-of-range functions for saccharolytic fermentation, butyrate production, acetate production, and GABA, a critical neurotransmitter to induce calming effects and relaxation, and assists with sensory processing. Indole plays a role in maintaining intestinal homeostasis and regulating the mucosal barrier function, which affects immune responses and the balance of beneficial and pathogenic bacteria within the gut, and this was found to be low. Indole influences the production of B vitamins: B2, B9, and B12, and despite having a negative MTHFR SNP, it may explain the low production of B vitamins, and the need for supplementation. Saccharolytic fermentation was so low at 145, with a healthy range between 535 and 1573. The fermentation process of the microbiome is essential to produce short-chain fatty acids. Low production in saccharolytic fermentation interferes with gut barrier function and health. The impaired gut barrier function directly affects the immune system, leading to inflammation and creating negative implications for the gut-brain axis.10,13
He completed the Cyrexiii Autoimmune reactivity test, with elevated antibodies to intrinsic factor, indicating low production of B12. The Cyrex Pathogen Associated Immune reactivity screen for multiple pathogens was within the normal range. He completed the Cyrex Blood Brain Barrier Screen, and it too revealed a normal result for IgG, IgA, and IgM.
Interventions
The first step to lower inflammation is to eliminate the source. He did so by changing his occupation and cleaning his living environment of the mold. The patient independently researched how to eliminate mold, identified the sources in his home, and cleaned them according to standard protocols.
He was provided with an anti-inflammatory diet, which benefits people with mental disorders and neurodegenerative diseases.8 The diet included fruits, primarily berries, vegetables and leafy greens, whole grains, legumes, fatty fish rich in Omega 3, nuts (especially walnuts), olive oil, and fermented foods such as plant-based yogurts, and kimchi, to name a few sources to support low fermentation. The antioxidant diet, fiber, and bioactive compounds are known to modulate inflammation and improve gut health, along with neuroprotective properties. Examples included whole grains such as quinoa, black rice, black beans, kidney beans, pinto beans, green peas for legumes, and a variety of nuts including walnuts, pecans, flax seeds, chia seeds, and turkey, duck, salmon, sardines for proteins. For healthy fats, he was advised to consume olive and avocado oils. He was encouraged to eat a variety of vegetables with a focus on leafy greens, spinach, arugula, and all cruciferous vegetables.7,8
He was advised against eating processed foods, sugar, and any of the foods on his laboratory list of intolerances. He eliminated the foods to which he was allergic. He will eat foods rich in prebiotic fibers and antioxidants to aid in the release of toxins. He was encouraged to drink from clean water sources. He was advised to hire a mold remediation company to assist with cleaning mold from his environment, which he declined due to the expense. He did choose to remediate on his own. He researched and adopted methods recommended by various internet sources and referenced respected sources, such as the Department of Health and the Environmental Protection Agency.
He attended our health counseling sessions, which were scheduled throughout his stay with our practice to provide assessments and follow-ups on compliance and outcomes to the treatment plan. He attended sessions on a monthly and sometimes bi-monthly basis with decreasing frequency until he reached the point of discharge in 2024. At the beginning, he was advised to work using an industrial-qualified mask and gloves, or to consider an alternative occupation. Eventually he did change his occupation. Part of our work together included psychoeducation and how to sustain behavior changes over time. He was educated on the role of the microbiome in the production of neurotransmitters and the proper functioning of the immune system. He was educated about the role of toxins and increasing markers of inflammation, and the symptoms of inflammation. He was informed about mold, Clostridia species, and Candida metabolites that act as toxins affecting inflammation, and especially how they cause issues in brain functioning, leading to psychiatric symptoms. The psychoeducation was helpful in compelling motivation and compliance with the plan.
The gut-brain axis involves many pathways, including but not limited to the autonomic and enteric nervous system, endocrine and the hypothalamic-pituitary-adrenal axis, the immune system, and the microbiota and their metabolites, some of which are toxins. Vitamins, neurotransmitters, bile acids and amino acids, and the short-chain fatty acids modulate many immune system pathways, which ultimately affect behavior, memory, and learning, leading to psychiatric and neurodegenerative disorders. Many researchers have shown that the inflammasome, which is the sensor that initiates the activation of the immune system, plays a role in anxiety, depression, and schizophrenia, to name a few psychiatric diagnoses. Furthermore, the activation of C4a from the inflammasome is linked to changes in the prefrontal cortex.10,13 Functioning immune cells can enter the CNS (central nervous system) through the BBB, along with the molecules that can pass, such as bacterial products and their metabolites.9,14,15 A bidirectional mechanism exists between the gut and the brain, sending signals from the microbiome to the brain, and this gut-brain axis is widely documented in several studies.3,4,6,16,17
The Prescribed Plan
- NAC (N-Acetyl Cysteine) 600 mg, L-Glutathione 375-750 mg (must be liposomal type for improved absorption) to address the elimination of toxins and resolve the low level of glutathione. Dosing was once daily.
- Binders during detoxification, such as the fiber, Glucomannan 2 g, have shown efficacy in binding various mycotoxins, and fiber was taken daily up to 2 grams. Two tabs of Spore probiotics and prebiotics (of 4 billion CFU) were prescribed with a meal to support the microbial re-colonization in the gut and help produce the neuro-hormones and re-establish balance.
- Chlorella 2 ml is a heavy metal and aflatoxin binder.
- plantarum C88 10billion CFU. This strain works not only to bind to aflatoxins, but it also works by upregulating the antioxidant activity of glutathione S-transferase.
- Magnesium 300 mg, L-Theanine 200 mg, and pharma GABA 100-300 mg to support calm and more restful sleep.
- D3, 5000 IU daily for two weeks, thereafter 2000 IU daily (vitamin D3 is reputed to have many functions in various systems, including the effect of reducing inflammation and improving mental health).
- Methylated B Complex to support the production of neuro-hormones.
- CoQ10 500mg to support antioxidant activity.
- Boulardii 10 billion CFU and Nystatin RX 500 000 IU two tabs twice daily for yeast overgrowth (use for three months, test, then terminate or extend treatment based on results).
Follow-Up and Outcomes
Two to three months into the treatment plan (11-2022), he reported that he was feeling much better and had no acute symptoms of schizophrenia. A routine mental status was performed using questions and an internal checklist with symptoms rated from mild, moderate, to severe. He rated his symptoms of psychosis as none. He stated that he felt better physically and could focus and concentrate. He was no longer on any medication and had a complete remission of all his psychiatric and physical symptoms.
02/02/2023: He repeated lab tests, his C3a returned to normal, while his C4a decreased from 4546.8 to 917.8. He remains intolerant to many foods, likely the result of his poor gut health. He was allergic to wheat, peanuts, and soybeans. He was intolerant of Candida. The Candida albicans was lowered from 0.71 to 0.59 owing to the Nystatin treatment.
10-19-2023: He repeated the labs, and all parameters were within the normal range except for a slight elevation of alkaline phosphatase at 127 (44-121 IU/L). Candida was further lowered, from 0.59 to 0.21. Nystatin treatment was discontinued given the lower levels and positive outcomes.
02/28/2024: All repeat labs using standard lab testing were within normal limits. CBC and CMP results were normal. His VMA 24-hour Urine test was within normal limits. C4a was lower at 651.8, proving that the treatment to lower inflammation was successful.
He was compliant with the food plan, medication, and supplements. All supplements were stopped six months after initiation, except for Vitamin D3, CoQ10, and Vitamin B complex. He continued using glucomannan, L-Theanine, and GABA as desired for a calming effect.
The assessment of his outcomes included the MSQ (Medical Symptom Questionnaire) and the MSE checklist, as well as clinical interviews to document his results. The Institute for Functional Medicine MSQ score lowered from 62 (6-2022) to 34 (9-2022), and further to 6 (6-2024), indicating a substantial decrease in symptoms over time, confirming the positive outcomes from the treatment approach.
He reported being adherent to the food plan and doing daily exercise at the gym. After the treatment plan, he was off all psychiatric medications, never hospitalized again for two years following the plan in 2022, and as evaluated in 2024. He reported positive outcomes because of the plan, and that he had never felt as healthy both mentally and physically. He did not experience any side effects from the treatment plan.
Discussion
The patient had losses in his life as an adolescent, and that, coupled with poor diet and lack of exercise routines, made it extremely challenging for his system to tolerate any major stressors. Additional antecedents were the family history of immune system dysfunction with autoimmune diseases and the likelihood that he, too, was genetically predisposed. As a young adult, he experienced a major stressor as he was involved in legal trouble, but was absolved of it, and his name was cleared. He described it as a very stressful event in his life, but it did not lead to any significant psychiatric symptoms. The major stressors in his life triggered a breakdown of many metabolic processes typical of chronic high levels of cortisol, such as neuroendocrine imbalances.
The series of traumatic events, coupled with a job in which he experienced an overload of toxins, led to deterioration. From a psychosocial viewpoint, he was not caring for himself during these high-stress episodes. His diet was not adequate or wholesome. The pattern of poor self-care led to chronic inflammation and poor gut health. The patterns included poor dietary choices and a lack of protective equipment to wear during exposure to toxic chemicals. These mediators fueled the ongoing downtrend in his health. His symptoms of chronic inflammation included weariness, fatigue, daytime sleepiness, irritability, and cognitive components, such as pain and disease activity.18
The lack of positive or sustained symptom relief from conventional approaches indicates that the traditional explanations for psychiatric disorders do not apply in this case, or likely in most cases, as symptoms are rarely, if ever, remitted to the extent that the recipient reports a return to “normalcy”.
An alternative approach to conventional treatment is examining the effects of toxins, which trigger inflammation that leads to changes in brain chemistry and functioning. He was exposed to toxins such as xylene and other unknown chemicals in oil-based paints during his job, and mold toxins in his home. Chronic inflammation from the toxins is a risk factor for mental health disorders.14,19,20
Based on his history and assessment, it is likely that a build-up of toxins has interfered with the healthy functioning of various systems. The history of his losses and stressful events set into motion a shifting of metabolic processes from the baseline of optimal to borderline functioning. Precious metabolic resources were being used to maintain daily functioning. Since additional assaults occurred in the form of a toxin-laden job, he could no longer maintain daily functioning. He then entered the realm of traditional psychiatry with multiple biochemical interventions that did not produce any relief.
He was tested for dysbiosis, and the positive finding was associated with chronic inflammation. Dysbiosis not only leads to gastrointestinal disorders but also affects distal organs. Intestinal bacteria can affect the central nervous system. There exists a bidirectional network of signaling pathways along the gut-brain axis through multiple connections in the vagus nerve, the immune system, and bacterial metabolites and toxic products cause dysregulation of these pathways.3
Chronic low-level inflammation is a mediator of neuroinflammation. The chronic level of inflammation interferes with synapses in the brain, as immune cells are believed to do “pruning” of cells.10 The pruning of cells in the prefrontal cortex will lead to the common symptoms of schizophrenia, such as a decrease in logical and rational thinking and changes in sensory perception.
His case illustrates the need for a systems review of the possible causes of mental health and physical anomalies. When the mind is not well, neither is the body. When the body is in poor health, so is the brain/mind. The integrative and whole-brain-body systems approach provided a new path to explore. His career change, along with the introduction of detoxifying supportive supplements and an anti-inflammatory diet, improved the functioning of both mind and body. The focus on inflammation in this case is warranted, given the research findings of the impact of chronic inflammation on the production of various diseases, including depression, bipolar depression, anxiety-related disorders, and schizophrenia.14
The normal catecholamines test result of serotonin, epinephrine, dopamine, and Vanillylmandelic acid (VMA) raises the question whether mental health diagnoses are truly the result of varying levels of serotonin and/or dopamine or are the imbalances in neurohormones produced by other core triggers? If it is due only to specific neurotransmitter imbalances, then medications that solely focus on one or two neurotransmitters should work across the board. Instead, we find that there is some symptom relief for a few, but seldom without side effects.2 This case study highlights the likelihood of other issues that need to be addressed to restore normal functioning of the brain and body. We should not ignore the high levels of inflammation that are common in every disease, and should have a plan to address it.
The therapeutic plan aimed to remove the sources of inflammation, namely the chemical toxins on the job, non-organic and processed foods, and mold. The treatment helped calm the state of inflammation, along with detoxifying glutathione and the precursor of NAC to support the ongoing production of natural glutathione and antioxidants in the form of CoQ10. Vitamin D3 is known to support the immune system, and B vitamins support metabolic processes throughout the body.
S. Boulardii and L. plantarum help regulate dysbiosis and restore a more stable gut-brain axis, thus improving mental health.11 Fiber has many healthy supportive functions in the gut and acts as a binder of aflatoxins, which are another source of toxins produced by molds. Magnesium, L-Theanine, and GABA are known to promote calmness and help restore sleep, crucial for healthy brain functioning.21
The strengths of the case study are the length of the follow-up and having achieved the identified objectives, which were to seek a cure for his psychiatric symptoms without medication or hospitalization. The treatment itself was efficacious and required only simple changes in lifestyle (such as diet, exercise, and supplements prescribed to normalize metabolic processes) as opposed to the costly and ineffective treatments, including multiple hospitalizations and chronic use of psychiatric medications.
This study has a few limitations. Firstly, this is a single patient case study. Secondly, the mold infestation could not be documented with real data, except for reports associating higher levels of mold toxins with a downstream metabolite.
The positive aspect of the case study is that a well-supported model with a different approach is outlined, illustrating how the approach worked, supported with lab results, and achieved a reduction in inflammation. The approach not only achieved its goals but also supported overall health, since chronic inflammation is also associated with other illnesses.18,19 The patient’s case clearly illustrates the track towards repeated failed outcomes for him with yearly or more frequent psychiatric hospitalizations and a multitude of medications that by themselves could and would lead to other metabolic anomalies. Additionally, an economic burden is associated with hospitalizations and chronic use of medications that do not lead to a cure.1,2 The patient is functioning well, happy, and productive, without any additional costs for hospitalizations and medications.
Subject’s Perspective and Comment
Hello Dr. G,
After completing my treatment plan, I have had zero psychiatric hospitalizations, no use of psychiatric medications, and no return of any original symptoms.
I realized a total recovery in my mental and physical health. I realized a total improvement in my physical health by removing wheat and dairy from my diet, and on a scale of 1-5, how well I am doing and achieved my goals, I would give it a 5. Because of your treatment and the work you did, I have been able to identify that toxins are extremely dangerous for me, and I changed my line of work. In addition, I was able to solidify that I didn’t have a mental illness. I had medical issues that were masking themselves as mental illnesses.
Funding
The research received no funding of any kind
Ethics Statement
Informed consent was obtained from the subject.
Author Disclosure Statement
The authors declare that they have no competing interests.
Acknowledgements
The Case report followed the Care Guidelines. IFM Matrix, Clinical Imbalances used with Permission from the Institute for Functional Medicine (IFM), the global leader in functional medicine and a collaborator in the transformation of healthcare.
References
- Fair Health. Analysis of healthcare costs in the United States [White paper]. 2024. Accessed June 27, 2025. https://www.fairhealth.org/research/white-papers/analysis-healthcare-costs
- Leichsenring F, Steinert C, Rabung S, Ioannidis JPA. The efficacy of psychotherapies and pharmacotherapies for mental disorders in adults: an umbrella review and meta-analytic evaluation of recent meta-analyses. World Psychiatry. 2022;21(1):133-145. doi:10.1002/wps.20941
- Rutsch A, Kantsjö JB, Ronchi F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Front Immunol. 2020;11:604179. doi:10.3389/fimmu.2020.604179
- Beurel E, Toups M, Nemeroff CB. The Bidirectional Relationship of Depression and Inflammation: double Trouble. Neuron. 2020;107(2):234-256. doi:10.1016/j.neuron.2020.06.002
- Belliveau R, Horton S, Hereford C, Ridpath L, Foster R, Boothe E. Pro-inflammatory diet and depressive symptoms in the healthcare setting. BMC Psychiatry. 2022;22(1):125. doi:10.1186/s12888-022-03771-z
- Harsanyi S, Kupcova I, Danisovic L, Klein M. Selected Biomarkers of Depression: What Are the Effects of Cytokines and Inflammation? Int J Mol Sci. 2022;24(1):578. doi:10.3390/ijms24010578
- Swainson J, Reeson M, Malik U, Stefanuk I, Cummins M, Sivapalan S. Diet and depression: A systematic review of whole dietary interventions as treatment in patients with depression. J Affect Disord. 2023;327:270-278. doi:10.1016/j.jad.2023.01.094
- van Zonneveld SM, van den Oever EJ, Haarman BCM, et al. An Anti-Inflammatory Diet and Its Potential Benefit for Individuals with Mental Disorders and Neurodegenerative Diseases-A Narrative Review. Nutrients. 2024;16(16):2646. doi:10.3390/nu16162646
- Verma A, Inslicht SS, Bhargava A. Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders. Cells. 2024;13(17):1436. doi:10.3390/cells13171436
- Yilmaz M, Yalcin E, Presumey J, et al. Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice. Nat Neurosci. 2021;24(2):214-224. doi:10.1038/s41593-020-00763-8
- Huang L, Zhao Z, Duan C, et al. Lactobacillus plantarum C88 protects against aflatoxin B1-induced liver injury in mice via inhibition of NF-κB-mediated inflammatory responses and excessive apoptosis. BMC Microbiol. 2019;19(1):170. doi:10.1186/s12866-019-1525-4
- Sun Y, Koyama Y, Shimada S. Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation? Front Aging Neurosci. 2022;14:903455. doi:10.3389/fnagi.2022.903455
- Ebrahimi M, Teymouri K, Chen CC, et al. Association study of the complement component C4gene and suicide risk in schizophrenia. Schizophrenia (Heidelb). 2024;10(1):14. doi:10.1038/s41537-024-00440-w
- Goldsmith DR, Bekhbat M, Mehta ND, Felger JC. Inflammation-Related functional and structural dysconnectivity as a pathway to psychopathology. Biol Psychiatry. 2023;93(5):405-418. doi:10.1016/j.biopsych.2022.11.003
- Mou Y, Du Y, Zhou L, et al. Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging. Front Immunol. 2022;13:796288. doi:10.3389/fimmu.2022.796288
- Tan HE, Chian LK. The microbiota-gut-brain axis in stress and depression. Front Neurosci. 2023;17:1151478. doi:10.3389/fnins.2023.1151478
- Naufel MF, Truzzi GM, Ferreira CM, Coelho FMS. The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders. Arq Neuropsiquiatr. 2023;81(7):670-684. doi:10.1055/s-0043-1767818
- Louati K, Berenbaum F. Fatigue in chronic inflammation – a link to pain pathways. Arthritis Res Ther. 2015;17(1):254. doi:10.1186/s13075-015-0784-1
- Daiber A, Münzel T. Special Issue “Impact of environmental pollution and stress on redox signaling and oxidative stress pathways”. Redox Biol. 2020;37:101621. doi:10.1016/j.redox.2020.101621
- Dudzińska E, Szymona K, Bogucki J, et al. Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naïve Patients. J Clin Med. 2022;11(9):2551. doi:10.3390/jcm11092551
- Pizzorno JE, Murray MT. Textbook of natural medicine.5th ed. Churchill Livingstone; 2020.

Leave a Reply