How Gut Issues Can Lead to Psychosis and Schizophrenia
Reading through a 2015 study on gastroenterology issues in schizophrenia, “Gastroenterology issues in schizophrenia: why the gut matters”, it is shocking (and concerning) to see how much correlation there is to stomach problems (such as IBS, Crohn’s, Leaky Gut, etc.) and mental health issues (psychosis, schizophrenia, manic episodes, etc.)
This day in age, it’s hard to take care of our gut, with busy schedules almost demanding a diet that is ‘convenient’, ie. filled with processed foods.
Alcohol doesn’t help either. It kills and disrupts the good bacteria in our gut. Good bacteria which communicates with our brain to regulate our mood (through signaling to release compounds such as serotonin, dopamine, and regulate your mood, generally in positive ways). This is just one example of how what we ingest can affect our mood, through neurotransmitters such as serotonin (1). (Side Note: Alcohol is almost always detrimental, with many more negative effects. It’s OK to consume it once a month or so, but anymore than that and you are negatively affecting your body).
Anyways, here are some notes I took when reading through through this study, which may provide some clarity on how stomach issues and psychosis are related:
Introduction
In a series of research reports, we have united conceptually and experimentally a number of risk factors for the development of schizophrenia through a common origin in the gut. The disease-associated interaction of such biological variables as humoral immunity to food antigens, intestinal inflammation, exposure to the parasite Toxoplasma gondii, endothelial barrier defects and microbial dysbiosis is consistent with a physiological model whereby gut-based processes can create a systemic state of immune dysregulation. The resulting immune response causes the activation of adaptive and innate immunity of molecules and factors that are important to a properly functioning brain.
History of GI comorbidities in schizophrenia
Biochemical and physiological evidence in favor of a GI etiology for psychiatric illness has been accumulating more or less continuously since 1860. Such investigations included those of Herter (1907), who found indication of low stomach acid in patients with mental illness, along with bacterial putrefaction (rotting) of various amino acids including tryptophan. One function of gastric juices is to maintain a proteolytic environment [breaking proteins or peptides into simpler and soluble products] to enzymatically control proliferation of anaerobic bacteria to the small intestine and prevent the absorption of toxins. Herter’s findings have interesting physiological ramifications given that tryptophan and the other aromatic amino acids phenylalanine and tyrosine are precursors of schizophrenia-relevant neurotransmitters including serotonin, dopamine, epinephrine, and norepinephrine. Thus, any interference by putrefactive bacteria would reduce the physical bioavailability of these amino acids and subsequent production of neurotransmitters critical to normal neuronal function. Furthermore, this process of putrefaction would result in the production of highly toxic substances that in theory could be differentially absorbed depending on individual, perhaps genetic, susceptibilities. With these studies laying the historical framework for GI-based issues relevant to the schizophrenia, scientists are now re-conceptualizing the association between dysbiosis-based autointoxication and related processes in relationship to psychiatric disease, cognitive function and neuroinflammation.
GI inflammation
In an autopsy study of 82 patients with schizophrenia, it was reported that 50% had gastritis, 88% enteritis and 92% colitis. These are surprisingly high incidence rates, and more modest, but still significant case control differences are evident when narrowing the diagnosis down to specific GI subgroups. For example, in IBS, reportedly 19% of people with schizophrenia had IBS compared to a rate of 2.5% in the control group. In the reverse analysis, up to 54 to 90% of IBS patients may have a psychiatric comorbidity, typically in the form of a mood or anxiety disorder. Biochemical aids for the diagnosis of GI diseases such as Crohn’s Disease include the measurement of anti-Saccharomyces cerevisiae antibodies (ASCA). In previous work, we found that an elevated ASCA response indicative of GI inflammation was significantly associated with schizophrenia and particularly in those with a recent onset of the disease compared to controls. Furthermore, in a second cohort, patients with schizophrenia who were antipsychotic-naïve had markedly elevated ASCA levels compared to medicated individuals with schizophrenia. These results echo historical findings of a GI relevance to mental illness in acute vs chronic cases and support that it is in the early stage of schizophrenia where GI inflammation inherent to the disease may be most evident.
Diet-based immune sensitivity
F. Curtis Dohan prolifically disseminated the idea that wheat availability was strongly correlated with hospital rates for schizophrenia, with his interest in this area stimulated by his observations of post-war Europe. Mechanistically, Dohan and others have proposed that gluten is broken down into bioactive opioid receptor peptides that may penetrate the GI and brain structural barriers.
The dietary removal of gluten has met with varied results in schizophrenia and also autism, most likely a reflection of the extreme heterogeneity of both disorders. The most success in improving symptomatology was observed in those instances where inclusion criteria required that candidates have evidence of gluten or diet-related sensitivity.
By thematic extension, other food antigens such as milk caseins also produce bioactive exorphins and exposure to these peptides are similarly applicable in studies of brain disorders. Elevations in milk casein antibodies are evident in individuals with schizophrenia compared to controls and in some cases, these milk antibodies are increased up to two years prior to diagnosis.
- (NOTE: Something which might be worthwhile to test and keep track of, if one is at risk of, or suspects, schizophrenia)
The gut-immune-brain interactome in schizophrenia
Schizophrenia is phenotypically a brain disorder; thus any consideration for a role of the GI system in its etiology or pathophysiology must include a mechanism that impacts the brain. The hypothesis that toxic and bioactive products escape the GI tract, produce an immune response and enter the brain requires the ability of these and associated products to penetrate epithelial and endothelial barriers in both the GI tract and at blood-central nervous system (CNS) interfaces. Daneman and Rescigno (2009) provide an exquisite review of how the gut immune barrier and the blood-brain barrier are functionally and structurally similar.
Inflammation, infection and stress are environmental factors that can impact the integrity of epithelial and endothelial barrier structures.
- (NOTE: Stress has a huge effect on our health, much more than people imagine. Inflammation can be caused by pain (which is why it’s important to stretch, and other inflammation-reducing activities, such as eating healthy, drinking chlorophyll, etc). Minor infections aren’t bad, but chronic and/or serious infections can weaken our system, and open us up to other, more serious, illnesses).
Inflammation, particularly of a low-grade nature, is a consistent pathological finding in schizophrenia, and as described earlier, some of this inflammation is associated with the GI tract. Interestingly, T. gondii exposure is a well-documented risk factor for schizophrenia.
In our studies of clinical samples, we found correlations between levels of T. gondii IgG with food antigen IgG in people with a recent onset of schizophrenia, which were not present in control groups.
In a rodent model, we verified that GI disruption due to T. gondii infection leads to the production of anti-gluten antibodies in infected animals. Thus, once gut barriers have been compromised, bacteria and other bacterial- or food-derived products can be translocated into the general circulation, and a state of low-grade inflammation is initiated and perpetuated. Consistent with this process, we have found that markers of bacterial translocation were indeed altered in schizophrenia, and this finding was independent of antipsychotics.
Conclusion
We can see how diet is important, not just for a healthy heart, or looks, but for other reasons. In Chinese medicine, the root of all health is the stomach. I think this approach, stemming from a practice with 3000 years of observation, is worth noting.
How can you start healing your gut? Everybody is different (genetics, environment, blood-type, age, medical history, etc.) however an approach of killing off the bad bacteria, adopting an anti-fungal diet in most cases, and taking probiotics is a simple, effective approach. The exact details are far beyond the scope of this post, but if you’d like to learn more please reach out via the contact form and I’d be glad to help.
References:
- What Alcohol Does to Your Body, Brain & Health | Huberman Lab Podcast #86 (@54:24)
- Gastroenterology issues in schizophrenia: why the gut matters. Emily G. Severance, Ph.D., Emese Prandovszky, Ph.D., James Castiglione, M.L.I.S., M.S., and Robert H. Yolken, M.D.