Anti-inflammatories May Promote Brain Function in Patients with Schizophrenia

Inflammation may play an important role in patients with schizophrenia, new research determined, which could lead to improved treatments.

The etiology of schizophrenia is still largely unknown and a recent study evaluated if it is neurodevelopmental or neurodegenerative condition. Yet, many suspect that early neurodevelopmental anomalies may interact with typical brain maturation processes throughout a patient’s adolescence, causing some relatively benign markers of developmental disruption.

Molecular Psychiatry

Another recent study, this one in , looked at cytokine levels of patients with schizophrenia in an attempt to determine the extent to which elevated peripheral cytokine messenger RNA (mRNA) expression characterizes certain patients with schizophrenia and shows a relationship to cognition and brain function and symptoms. They found evidence that targeted anti-inflammatory treatments may help lessen cognitive and brain abnormalities in certain patients with schizophrenia.

The research borrows an idea used to research other disease in which elevated cytokine levels and inflammation have been linked to disease severity, including Alzheimer’s disease.

“Group comparisons of peripheral circulating cytokines (signaling peptides of the immune system mediating the inflammation response) between individuals with schizophrenia and controls have consistently identified higher mean levels of interleukin (IL)-6, IL-1β, tumor necrosis factor and other cytokines in schizophrenia and even greater elevations during acute psychosis,” the study authors noted.

The researchers suggested that demonstrating that a proportion of individuals with schizophrenia have abnormal cytokine profiles in blood, similar to what other studies have shown in post-mortem brain samples, would further support the relevance of inflammation to pathophysiology in a subgroup of those with the disease.

Forty-three outpatients with schizophrenia or schizoaffective disorder and matched healthy controls were assessed for peripheral cytokine mRNAs (interleukin (IL)-1β, IL-2, IL-6, IL-8 and IL-18). The researchers also measured intelligence quotient, memory and verbal fluency, symptom severity and cortical brain volumes integral to language.

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Compared with controls, patients with schizophrenia had IL-1β mRNA levels 28 higher. Then, using a two-step clustering procedure, the clinicians identified a subgroup of people displaying relatively elevated cytokine mRNA levels (1743 people with schizophrenia and 942 controls). Individuals with schizophrenia in the elevated cytokine subgroup performed significantly worse than the low-cytokine subgroup on verbal fluency (<0.001). There was a 17 volume reduction of the left pars opercularis (POp) (Broca’s area) in patients with elevated cytokines compared with patients with lower cytokines (F(1,29)9.41, 0.005).

The association was not the same for the other mRNAs. This was not surprising because IL-1β is a powerful classical proinflammatory cytokine, which has been described as a master regulator of other immune cells and immune processes.

“This study is among the first to link blood biomarkers of inflammation with both cognitive deficits and brain volume reductions in people with schizophrenia, supporting that those with elevated cytokines represent a neurobiologically meaningful subgroup,” the study authors concluded. “These findings raise the possibility that targeted anti-inflammatory treatments may ameliorate cognitive and brain morphological abnormalities in some people with schizophrenia.”