Mental Illness: Looking Beyond the Diagnosis

When I was in medical school and residency, conditions such as anxiety, depression, schizophrenia, and bipolar disorder were generally viewed as primary psychiatric illnesses and little else. Outside of a handful of well-recognized exceptions—such as systemic lupus erythematosus (SLE), certain medications known to cause psychiatric side effects, or substance abuse—there was relatively little emphasis on searching for an underlying medical cause.

At that time, the pharmaceutical industry had considerable influence on medical education. The result was often a "pill for every ill" approach in which the focus was placed on assigning a diagnosis, prescribing medication, and recommending counseling.

Fortunately, medicine has evolved. We now understand (and are taught) that many psychiatric disorders have an organic basis involving the brain, immune system, endocrine system, metabolism, nutrition, or infectious disease. Rather than simply assigning a psychiatric diagnosis, we should always ask an important question:

Why did this person develop these symptoms?

Finding and treating the root cause, when possible, should always be part of the evaluation.

This does not diminish the importance of psychiatric medications or counseling. Both can be lifesaving and are often essential components of treatment. However, they should not replace a thorough medical evaluation when an underlying cause may be present.

Of course, psychiatric illness can also be triggered by adverse childhood experiences, psychological trauma, chronic stress, or major life events. Likewise, nutritional deficiencies or excesses, hormonal disorders, metabolic disease, toxic exposures, and sleep disorders may all contribute to alterations in brain function and mental health. Further, an emerging cause of mental illness seen in Generation Z, particularly in English-speaking and Nordic countries, may be related to social media, the digital age, changes in parenting, and other societal factors.1 

Although therapy can be helpful, the root cause(s) of mental illness should be explored and addressed.

Infections and Mental Illness

The relationship between infection and psychiatric disease has become an area of increasing research.

A comprehensive review published in 2023 examined the evidence linking mental illness with a wide range of infectious pathogens, including parasites, fungi, bacteria, and viruses.2 The authors summarized decades of published research and provided excellent tables cataloging the individual pathogens that have potential associations with psychiatric disorders, along with references to the supporting scientific literature. This review serves as a valuable resource for clinicians and researchers interested in the growing body of evidence connecting infectious diseases, immune dysregulation, and mental illness.

A study published in May 2026 examined individuals with severe mental illness and compared infection-related mortality with matched control subjects.3 The investigators found that people with severe mental illness experienced higher mortality from respiratory, gastrointestinal, and renal/urinary tract infections than matched controls.3 While the absolute number of infection-related deaths was relatively small, the increased risk was observed across most categories of infection, with the exception of skin infections.3

The study also found that severe mental illness was more common among individuals with chronic medical conditions, obesity, and Black participants.3 Importantly, this study does not demonstrate that infections cause severe mental illness. Rather, it highlights a significant association between severe psychiatric disease and an increased burden of serious infections.

This finding raises an important question: Could infections contribute to mental illness in at least some patients?

There are several biologically plausible mechanisms by which this could occur. Some infections directly invade the central nervous system, while others may trigger persistent immune activation, chronic inflammation, or autoimmune responses that affect brain function. Researchers continue to investigate these mechanisms, and although many questions remain unanswered, the connection between infection, immune dysregulation, and psychiatric illness has become an area of intense scientific interest.

Immune Dysregulation, Autoimmune Disease, and Mental Illness

Autoimmune disease represents only one form of immune dysregulation. In reality, immune dysregulation is a much broader concept that includes abnormal activation or suppression of the immune system, chronic inflammation, and immune responses that may or may not meet the criteria for a classic autoimmune disease.

One proposed mechanism by which infections contribute to autoimmune disease is molecular mimicry. In this process, proteins from bacteria, viruses, or other infectious organisms resemble proteins naturally found in the human body. As the immune system produces antibodies against the infectious organism, those same antibodies may mistakenly recognize and attack the body's own tissues.

The idea that psychiatric disease could be associated with autoimmune disorders is not new. The hypothesis was first proposed in the 1930s and became an established subspecialty of internal medicine during the 1960s and early 1970s. As knowledge of autoimmune diseases expanded throughout the 1980s and 1990s, researchers increasingly recognized the association between systemic autoimmune diseases and psychiatric disorders.

Today, numerous studies have demonstrated associations between autoimmune diseases—including lupus, rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, autoimmune thyroid disease, and others—and psychiatric symptoms such as depression, anxiety, cognitive impairment, and psychosis. Many of these studies focus on psychosis, especially new onset, because it is a severe psychiatric condition with both subjective symptoms and objective clinical signs that can be directly observed by healthcare professionals.4 Unlike depression or anxiety, psychosis often includes hallucinations, delusions, or disorganized thinking that are readily identifiable during a clinical examination. Consequently, psychosis has become an important model for studying the relationship between immune dysfunction and brain disease.

Final Thoughts

As our understanding of immunology, neuroinflammation, infectious diseases, and autoimmune disorders continues to advance, the traditional separation between "medical" illness and "psychiatric" illness is becoming increasingly blurred. In many patients, psychiatric symptoms may represent one manifestation of an underlying medical disorder rather than an isolated disease of the mind alone.

The challenge for today's clinician is to recognize when psychiatric symptoms are primary and when they may be the consequence of a treatable underlying condition.

Resources

1. Armitage R. Books: The Anxious Generation: How the Great Rewiring of Childhood is Causing an Epidemic of Mental Illness: Gen Z and the meteoric rise in anxiety, depression, and self-harm. Br J Gen Pract. 2024 Jun 28;74(744):322–3. doi: 10.3399/bjgp24X738693. PMCID: PMC11221737.

2. Ronaldson A, Das-Munshi J, Dregan A, Lampejo T, Henderson C, Smith D, Bakolis I. Characterizing Infectious Disease Mortality in Severe Mental Illness: A Retrospective Matched Cohort Study. Schizophr Bull. 2026 Apr 10;52(3):sbag067. doi: 10.1093/schbul/sbag067. PMID: 42104801; PMCID: PMC13156512.

3. Bransfield RC, Mao C, Greenberg R. Microbes and Mental Illness: Past, Present, and Future. Healthcare (Basel). 2023 Dec 29;12(1):83. doi: 10.3390/healthcare12010083. PMID: 38200989; PMCID: PMC10779437.

4. Najjar S, Steiner J, Najjar A, Bechter K. A clinical approach to new-onset psychosis associated with immune dysregulation: the concept of autoimmune psychosis. J Neuroinflammation. 2018 Feb 13;15(1):40. doi: 10.1186/s12974-018-1067-y. PMID: 29433523; PMCID: PMC5809809.