Researchers have identified immune system dysregulation as a key differentiator between depression and psychosis, potentially opening new avenues for diagnosis and treatment of both conditions. The findings, emerging from studies conducted at the University of Bristol and the Francis Crick Institute, suggest that while both disorders exhibit altered inflammatory markers and brain structural changes, the specific nature of the immune response differs significantly.
The study published in Molecular Psychiatry builds on existing evidence linking mental health disorders to immune system activity. For years, scientists have approached mental health primarily as a neurological issue, focusing on neurotransmitters. However, this research indicates that inflammation and immune signaling may be central to the development of conditions like depression and schizophrenia, as well as Alzheimer’s disease and bipolar disorder.
Dr. Katharina Schmack, a psychiatrist and neuroscientist at the Francis Crick Institute, is currently leading a Wellcome-funded study investigating the effects of antipsychotic drugs on the immune system. Her function aims to determine whether antipsychotics modulate immune imbalances in psychosis, potentially leading to interventions that target the underlying causes of the condition rather than simply managing symptoms. “It’s challenging to know if a change in the immune system is a cause or consequence of the improvements we see in people with psychosis,” Schmack stated in a recent article published by Wellcome.
The research highlights the complexity of the immune system and the challenges in disentangling its role in mental illness. Early phases of both depression and psychosis are characterized by altered inflammatory markers in the blood and structural changes in the brain’s gray matter, according to Medical Xpress. However, the specific immune pathways involved appear to diverge, suggesting distinct underlying mechanisms.
Clinical trials are now being planned to test whether modulating the immune system can improve outcomes for individuals with mental health conditions. Pilot studies have indicated the potential of anti-inflammatory drugs – including NSAIDs, statins, and monoclonal antibodies – in alleviating symptoms in some patients experiencing depression or psychosis.
Christopher Hole, Akash Dhamsania, Cassandra Brown, and Rebecca Ryznar, authors of a review published in Cells in April 2025, detailed the interplay between immune dysfunction, cytokine activity, and neurotransmitter interactions in depression and anxiety. Their research also examined how current pharmacological and non-pharmacological interventions impact inflammation and immune responses.
The potential for new therapeutic strategies extends beyond simply identifying immune targets. Understanding how antipsychotics interact with the immune system, as Dr. Schmack’s study intends to reveal, could lead to treatments with fewer side effects. The Wellcome study is ongoing, with results expected to inform future research and clinical practice.
