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Schizophrenia is usually treated as a single disorder with a familiar set of symptoms and a standard biochemical explanation. Diana Kwon’s April 2025 Scientific American article argues that this picture is giving way to something more complicated and potentially more useful. Hallucinations, delusions and disordered thought may be the visible endpoints of several different biological processes. The future of treatment may therefore depend less on finding one universal cause than on identifying which form of illness each person has.

That shift matters because schizophrenia affects far more than a person’s immediate experience of reality. Psychosis—the hallucinations, delusions and disordered thinking often called “positive” symptoms—is the best-known aspect of the condition. Yet many people also live with “negative” symptoms such as emotional flatness, social withdrawal and diminished motivation, as well as difficulties with memory, attention and problem-solving. Traditional antipsychotics often control psychosis, but they do much less for these other problems, which can be the greater obstacle to everyday life.

Beyond the Dopamine Story

For decades nearly every antipsychotic drug worked by blocking dopamine, a chemical messenger involved in learning, motivation and habit formation. The drugs were a major advance over lobotomies and other destructive treatments, and they remain effective against psychosis for roughly two thirds of people with schizophrenia. Their success encouraged a simple theory: schizophrenia resulted from too much dopamine, so a different dose or another dopamine blocker should solve the problem.

The evidence now points to a more uneven pattern. Dopamine activity can be elevated in part of the striatum, a deep brain structure that helps people form associations. Excess activity there could encourage false connections and misperceptions. At the same time, dopamine can be reduced in the prefrontal cortex, impairing planning and emotional regulation. People who do not respond to conventional drugs may have different dopamine patterns from those who do. Researchers have also implicated glutamate, the brain’s main excitatory messenger; GABA, which inhibits neural activity; and changes in gray matter and synaptic density.

This broader view helps explain why dopamine blockers are both indispensable and inadequate. They can cause tremors, sedation, severe restlessness and weight gain that raises the risk of diabetes and cardiovascular disease. Charlene Sunkel, who began hearing voices and fearing that others could steal her thoughts at age 19, cycled through hospitalizations and medications with disabling side effects before clozapine finally improved her life. Even clozapine, the standard option for treatment-resistant schizophrenia, fails in many of the people who need it.

A new drug called KarXT, sold as Cobenfy, offers proof that psychosis can be treated through another route. It activates muscarinic receptors used by the neurotransmitter acetylcholine instead of directly blocking dopamine. Clinical trials found that it reduced psychosis and appeared to improve cognition without many of the side effects associated with dopamine blockers, although it produced mostly mild gastrointestinal problems and its long-term effects remain uncertain. Its importance is conceptual as well as clinical: if acting on a different receptor system can relieve the same symptoms, the traditional dopamine model is incomplete.

When Psychosis Begins in the Immune System

Some cases reveal an even more radical source of schizophrenia-like illness. April Burrell developed hallucinations and catatonia in her early twenties, received a diagnosis of severe schizophrenia and spent almost 20 years in a psychiatric hospital. A comprehensive medical workup eventually found autoantibodies attacking her brain. Doctors rediagnosed her with neuropsychiatric lupus, treated her immune system, and saw her make an almost full recovery.

Burrell’s experience is an extreme example, not evidence that most schizophrenia is autoimmune. Autoimmune encephalitis can produce sudden, severe psychosis, and researchers have identified more than two dozen autoantibodies that target the brain. Estimates suggest that about 1 percent of people with psychosis carry an antibody whose neurological target is already known. One German clinic that routinely examines cerebrospinal fluid has found uncharacterized neuronal autoantibodies in a much larger share of patients, but such antibodies also appear in healthy people, and their significance remains disputed.

Other clues nevertheless keep the immune system in the discussion. Infections have sometimes preceded psychosis; population studies associate repeated infections with greater schizophrenia risk; genetic studies implicate immune-related variants; and microglia, the brain’s resident immune cells, appear overactive in some patients. Trials are testing whether immunotherapies can help carefully selected people with neuronal autoantibodies. The promise is substantial, but so are the risks: suppressing immunity can cause serious side effects, and enthusiasm for a new mechanism should not obscure the fact that existing antipsychotics already help many people.

From One Label to Precision Care

The emerging picture resembles the transformation of cancer medicine. Cancer was once discussed as one disease; it is now divided into subtypes defined by tissue, mutations and molecular pathways, each matched to different treatments. Researchers increasingly suspect that schizophrenia should be approached in the same way—as a family of disorders united by overlapping symptoms but separated by underlying biology.

That would require psychiatry to look beyond symptoms alone. Some clinics already combine neuroimaging, blood tests and spinal-fluid analysis to rule out neurological and immune causes of psychosis, but this level of investigation is not routine. Large research programs are searching for biomarkers that might distinguish subtypes or identify the prodromal stage before full psychosis develops. Researchers are also exploring metabolic mechanisms, while cognitive-behavioral therapy can help some patients manage psychosis, depression, low motivation and reduced pleasure alongside medication.

The article’s central lesson is not that dopamine was a mistake or that one new theory has replaced it. It is that the same outward disruption of thought and perception can arise from different changes in brain signaling, immunity, metabolism, development and environment. A diagnosis that stops at the word “schizophrenia” may therefore conceal the information most needed for treatment. Progress will come from asking a more precise question: not simply whether a person has schizophrenia, but which biology is producing that person’s illness and which combination of care fits it.