The Link Between Inflammation and Schizophrenia

Schizophrenia is one of the most complicated health conditions to experience and treat. Characterized by hallucinations, emotional withdrawal and a decline in cognitive functioning, schizophrenia is a debilitating mental health disorder that affects nearly 50 million individuals worldwide. Although it has been recognized by the scientific community for more than a century, we have relatively few effective treatments for schizophrenia and little advancement has been made in schizophrenia treatment research.

One reason for the tepid pace may lie in the origins of the disease. The root cause of schizophrenia is thought to include a complicated mix of genetics, environment, and brain chemistry. Schizophrenia does not seem to discriminate on the basis of race, gender, or social status and onset typically occurs in the adolescent and young adult years. It can manifest differently depending on circumstances and severity of disease.


The road to finding effective treatment in each individual case of schizophrenia can be long and tedious. Antipsychotic medications are a mainstay, but there has been promising new research focused on the role that inflammation plays in schizophrenia. A 2015 study in the American Journal of Psychiatry revealed a direct link between inflammation and increased risk for mental health disorders. The study confirms that microglia – the immune cells used by the brain to fight inflammation- are much more active in individuals diagnosed with schizophrenia. Armed with this valuable insight, treatment protocols are turning towards Anti-inflammatory Combination Therapy.

“Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptoms who are at ultra high risk of psychosis and is related to at-risk symptom severity. These findings suggest that neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms.

— "Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [11C]PBR28 PET Brain Imaging Study." Bloomfield et Al. American Journal of Psychiatry,

 A 2019 meta- analysis investigated the use of adjuvant (supplemental) anti- inflammatory agents in the treatment of schizophrenia across 62 double blind, randomized, clinical trials. Their goal was to establish the effect these agents have on cognitive and general functioning and to identify any potential side effects. Current anti-psychotic medications used in the treatment of schizophrenia do a good job of addressing positive symptoms (e.g. hallucinations and hearing voices) of the disease, but a poor job in addressing negative (e.g. depressed mood and social withdrawal) and cognitive symptoms.

The anti-inflammatory agents examined in the review included aspirin, celecoxib, omega- 3 fatty acids, estrogen, selective estrogen receptor modulator, pregnenolone, N-acetylcysteine, minocycline, davunetide and erythropoietin

Researchers found that the anti-inflammatory agents were effective in reducing total positive and negative symptom scores. Other important findings included:

  • Cognitive improvements were significant with minocycline and pregnenolone augmentation therapy

  • General functioning was significantly enhanced by overall anti-inflammatory agents

  • There were no significant differences in side effects compared with placebo

The effectiveness of anti-inflammatory augmentation therapy was found to be mediated by two factors: severity of symptoms at baseline and duration of disease. Researchers concluded that using anti-inflammatory adjuvant therapy was more beneficial than treatment with antipsychotics alone. They recommend future research continue to investigate side effects of this type of therapy across the patient population.



NSAIDs and other anti-inflammatory agents help in treating schizophrenia because they work to quiet overactive immune system activity which drives the inflammation. As noted earlier, microglia in the brain release proteins called cytokines in response to chronic inflammation. These proteins bind to neurons, cause cell death, and disrupt normal brain functioning leading to changes in mood, cognition, and behavior.

Currently, the primary pharmacological treatment for schizophrenia focuses on the regulation of dopamine and not on the immune system. That tactic has proven useful in combating hallucinations and delusions (“positive” symptoms of schizophrenia). However, symptoms like low energy, lack of motivation, and poor concentration (“negative” symptoms) can remain unchecked. Sadly, approximately 25% of individuals do not respond to antipsychotic treatment at all. Medical experts hypothesize that combining pharmacological treatment with anti-inflammatory medicines could help with improving long-term response to treatment.

Research has revealed that the anti-inflammatory approach not only reduces symptoms, but also may help to prevent the development of neurobiological abnormalities if introduced early enough. Experts agree that further study is needed, but at this time there is a clear trend towards better treatment outcomes with the use of anti-inflammatory agents. 


In patients with psychotic symptoms and chronic inflammation, using NSAIDs and other anti-inflammatory agents along with medications could be an effective way to augment treatment and increase effectiveness. If you or someone that you know is dealing with schizophrenia, consider consulting with an integrative psychiatrist who can provide laboratory testing for inflammation levels and guide anti-inflammatory treatment.