I write frequently about mental health, as it remains one of the core focus areas of Viewpoint Foundation. For this issue of Invested, I wanted to step back and examine the question “what are the underlying causes of mental illness?”
For decades, mental illness has been framed primarily as a disorder of the brain, a matter of chemical imbalances, faulty neurotransmitters, misfiring neural circuits, or maladaptive thought patterns. This model has driven meaningful advances in psychiatry and neuroscience, improving treatment options and reducing stigma. Yet it has also narrowed the lens through which mental health is understood and addressed.
A growing body of research now suggests something far more complex, and, in many ways, more hopeful, is occurring. Many mental health conditions, or at least the symptoms that bring individuals into care, may originate outside the brain altogether. Immune dysfunction, viral infections, gut health, genetic vulnerabilities, and nutrient deficiencies are increasingly being linked to psychiatric symptoms. Rather than existing solely as neurological disorders, mental illnesses may reflect whole-body processes that interact dynamically with the brain.
This evolving evidence is reshaping how researchers, clinicians, and policymakers think about prevention, diagnosis, and treatment.
The Immune System and Mental Health
One of the most significant developments in mental health research is the growing recognition that the immune system may play a central role in psychiatric illness or its presenting symptoms. A recent large-scale study identified 29 immune-related proteins linked across seven major mental health conditions, revealing substantial biological overlap between immune dysfunction and disorders such as depression, schizophrenia, bipolar disorder, and obsessive-compulsive disorder. These findings challenge the notion that psychiatric illnesses exist in isolation from broader physiological systems (Neuroscience News, 2025).
Mounting evidence suggests that immune dysregulation (particularly chronic inflammation) can influence mood, cognition, and perception. Elevated inflammatory markers have been found in subsets of individuals with depression and anxiety, and immune-related genes appear to be shared across diagnoses traditionally viewed as distinct. Rather than representing entirely separate diseases with unique causes, some mental illnesses (or the presenting symptoms) may arise from common biological pathways rooted in immune imbalance (Gajbhiye, 2025).
A well-known example of this paradigm shift is documented in Brain on Fire, Susannah Cahalan’s memoir detailing her sudden descent into psychosis. After weeks of seizures, delusions, and erratic behaviour, she was initially diagnosed with schizoaffective disorder, a diagnosis that is given based on symptom observation as there is no definitive biological testing. It was only when neurologist Dr. Souhel Najjar suggested screening for anti-NMDA receptor encephalitis, a rare autoimmune condition discovered just a few years earlier, that the true cause was identified. At the time, it was estimated that only a small fraction of cases of anti-NMDA receptor encephalitis were correctly diagnosed. Once Cahalan received immune-targeted treatment, her psychiatric symptoms resolved. Had she continued to receive treatment solely for a psychiatric disorder, her recovery may never have occurred.
A similar case was reported in The New Yorker, describing a woman who had carried a diagnosis of schizophrenia for two decades before experiencing dramatic symptom remission while receiving immunosuppressive therapy for cancer. While such cases are not representative of all psychiatric illness, they highlight how immune-driven conditions can sometimes masquerade as primary mental disorders.
These examples are particularly striking given that approximately one-third of patients with depression and schizophrenia do not respond to traditional neurotransmitter-based medications. For decades, explanations for these conditions centred on monoamine neurotransmitters like serotonin and dopamine (Gajbhiye, 2025).
Researchers at the Korea Advanced Institute of Science and Technology (2025) have further demonstrated that both brain function and immune function appear excessively activated (and out of balance) in individuals with depression. Genetic analysis of immune cells revealed alterations that predispose the body to heightened inflammatory responses.
Taken together, the research points toward a more integrated understanding of mental illness and the presenting symptoms, one that situates the brain within a broader biological ecosystem rather than treating it as an isolated organ.
Viruses and the Brain
Another emerging area of research explores the role of viral infections in mental illness. Studies have detected viral traces in the cells lining the brain in individuals with conditions such as schizophrenia and bipolar disorder. Notably, researchers have identified evidence of hepatitis C virus (HCV) in tissues adjacent to the brain which challenges the long-standing assumption that the brain is largely insulated from systemic infection (Johns Hopkins Medicine, 2025).
Scientists at Johns Hopkins Medicine (2025) analyzed postmortem brain samples alongside the electronic medical records of 285 million patients. They found evidence of HCV in the brain’s choroid plexus which is the specialized tissue lining the ventricles that produce cerebrospinal fluid and helps protect the brain and spinal cord. HCV was detected in 3.5 percent of patients with schizophrenia and 3.9 percent of patients with bipolar disorder which is approximately seven times higher than in the control population, where prevalence was just 0.5 percent.
Although the virus was not found within deeper brain structures such as the hippocampus, its presence in the brain’s lining was associated with altered gene expression in the hippocampus which suggests that viral infection may influence brain function indirectly (Johns Hopkins Medicine, 2025).
The researchers were quick to point out that this does not mean that viruses “cause” mental illness. Rather, infections may trigger immune responses that alter brain function over time. For some individuals, psychiatric symptoms may reflect lingering inflammatory consequences of past infections rather than permanent structural abnormalities or chemical imbalances.
Our findings show that it’s possible that some people may be having psychiatric symptoms because they have an infection, and since the hepatitis C infection is treatable, it might be possible for this patient subset to be treated with antiviral drugs and not have to deal with psychiatric symptoms (Johns Hopkins Medicine, 2025).
Identifying and treating potential underlying infection may one day become a standard part of psychiatric care.
The Gut–Brain Connection
The gut–brain axis has moved from hypothesis to serious scientific inquiry. The trillions of microbes in the digestive tract are not passive bystanders, but active participants in regulating immune function, producing neurotransmitter precursors, and communicating with the brain through neural, and hormonal pathways (Nield, 2025).
Disruptions to the gut microbiome, whether from diet, chronic stress, antibiotic exposure, or illness, have been associated with anxiety and depression. Research suggests that gut inflammation and microbial imbalance may shape how the brain processes emotion and stress, particularly during sensitive developmental periods when neural circuits are still forming (Nield, 2025).
Recent research from identified six bacterial groups associated with obsessive-compulsive disorder (OCD). Three of which, Proteobacteria, Ruminococcaceae, and Bilophila were found to have a potentially protective relationship, while three others, Bacillales, Eubacterium, and Lachnospiraceae, were associated with increased risk. Researchers used Mendelian randomization to infer potential causal relationships between gut bacteria composition and OCD risk (Nield, 2025).
While promising, these findings remain early-stage and require validation through larger longitudinal studies across diverse populations.
Nutrient Deficiencies and Mental Health
Mental health is also deeply connected to basic physiology. A meta-analysis published in Molecular Psychiatry last year identified consistently lower levels of the essential nutrient choline in the brains of individuals with anxiety disorders, approximately eight percent lower than controls. While this number may appear modest, even small shifts in brain chemistry can meaningfully influence neural function (Petrova, 2025).
Importantly, the researchers found that this pattern was “transdiagnostic,” meaning it was observed across multiple types of anxiety disorders rather than confined to a single condition. The association held even after accounting for variables such as medication use, age, and technical differences in brain imaging methods, suggesting the finding may represent a robust biological marker (Petrova, 2025).
Choline plays a key role in building cell membranes and producing neurotransmitters involved in memory and mood regulation. And while the body can synthesize small amounts, most choline must be obtained through diet, including foods such as eggs, beef, chicken, soybeans, and fish, particularly fish such as salmon that is also rich in omega-3 fatty acids (Petrova, 2025).
Yet as we know, correlation does not equal causation. It remains unclear whether lower choline levels contribute to anxiety or result from it. Nevertheless, nutritional assessment and dietary interventions may complement traditional therapies.
Given that anxiety disorders affect roughly 30 percent of adults in the United States and remain undertreated, even modest improvements in prevention or management could have meaningful impact (Petrova, 2025).
Genetics, Environment, and the Whole-Body Model
A recent study led by researchers at the University of Colorado Boulder, Harvard University, and Mass General Brigham identified five shared genetic signatures across 14 psychiatric disorders. The findings suggest greater biologically interconnected than was previously recognised (Kozlov, 2025).
Many of the implicated genes are involved in immune regulation, metabolic function, and fundamental cellular processes rather than brain-specific pathways. This supports the idea that genetic vulnerability may influence how the body responds to stress, infection, and inflammation, with psychiatric symptoms emerging downstream (Koslov, 2025).
One particularly striking finding was the degree of overlap between schizophrenia and bipolar disorder. The researchers reported that approximately 70 percent of the genetic signal associated with schizophrenia is also associated with bipolar disorder. Historically, psychiatry has treated these conditions as distinct, and clinicians typically do not diagnose an individual with both. Yet genetically, they appear to share substantial biological architecture (Koslov, 2025).
As the researchers noted, psychiatric diagnoses today are largely based on observed symptoms. Many individuals receive multiple diagnoses, which can complicate treatment and feel disheartening for patients. This research provides compelling evidence that some disorders we currently label separately may, in fact, be driven by overlapping biological mechanisms (Koslov, 2025).
By identifying what is shared across conditions, rather than focusing exclusively on what differentiates them, researchers hope to develop more targeted interventions, potentially reducing the need for multiple medications or fragmented treatment approaches (Koslov, 2025).
Implications for Care and Policy
Traditional medications and therapies are ineffective for many people living with mental illness. Now with this new research showing the different root causes, we may finally be understanding why. Which is that many causes are physiological and require vastly different medications or approaches.
Viewing mental illness as a whole-body condition challenges siloed models of care and strengthens the case for integrated health systems that bridge mental and physical health. It also opens new avenues for prevention, early intervention, and personalized treatment through addressing potential chronic inflammation, nutritional deficiencies, or autoimmune disorders.
Perhaps most importantly, this shift reframes mental illness as a complex biological condition shaped by systems both inside and outside the brain.
As research continues to evolve, so too must the way we design mental health services and support innovation in care.
Bibliography
Gajbhiye S. (2025). Mental illness is caused by the whole body, not just the brain. https://www.earth.com/news/mental-illness-is-caused-by-the-whole-body-not-just-the-brain/
Johns Hopkins Medicine. (2025). New study finds evidence of hepatitis C virus in cells lining the human brain. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2025/07/new-study-finds-evidence-of-hepatitis-c-virus-in-cells-lining-human-brain
Kozlov, M. (2025). Huge genetic study reveals hidden links between psychiatric conditions. https://www.nature.com/articles/d41586-025-04037-w
Neuroscience News. (2025). Immune System Tied to Mental Health Disorders. https://neurosciencenews.com/immune-system-mental-health-28794/
Nield, D. (2025). OCD’s origins might not lie in the brain like we thought. https://www.sciencealert.com/ocds-origins-might-not-lie-in-the-brain-like-we-thought
Petrova, K. (2025). Anxiety disorders linked to lower levels of key nutrient. https://www.psypost.org/anxiety-disorders-linked-to-lower-levels-of-key-nutrient/
The Korean Advanced Institute of Science and Technology. (2025). Depression Tied to Immune System Imbalance, Not Just Brain Chemistry. https://medicalxpress.com/news/2025-11-depression-immune-imbalance-brain-chemistry.html