Can anti-inflammatory medications improve symptoms and reduce mortality in schizophrenia?

[ILLUSTRATION OMITTED] Consider 3 observations: * Evidence is mounting that cytokine abnormalities are present in schizophrenia (Box (1-8)). * Reduced arterial compliance (change in volume divided by change in pressure [[DELTA]V/[DELTA]P] in an artery during the cardiac cycle) is an early marker of cardiovascular disease (CVD) and a robust predictor of mortality, and is associated with cytokine abnormalities. * People with schizophrenia experience increased mortality from CVD. Taken together, the 3 statements hint at a hypothesis: a common inflammatory process involving cytokine imbalance is associated with symptoms of schizophrenia, reduced arterial compliance, and CVD. Anti-inflammatory therapeutics that target specific cytokines might both decrease psychiatric symptoms and reduce cardiac mortality in people with schizophrenia. In this article, we (1) highlight the potential role of anti-inflammatory medications in reducing both psychiatric symptoms and cardiac mortality in people with schizophrenia and (2) review the pathophysiological basis of this inflammatory commonality and the evidence for its presence in schizophrenia. The 'membrane hypothesis' of schizophrenia In this hypothesis, a disturbance in the synthesis and structure of membrane phospholipids results in a subsequent disturbance in the function of neuronal membrane proteins, which might be associated with symptoms and mortality in schizophrenia. (9-12) The synaptic vesicle protein synaptophysin, a marker for synaptic density, was found to be decreased in postmortem tissue from the gyrus cinguli in 11 patients with schizophrenia, compared with 13 controls. (10) Intracellular phospholipases [A.sub.2]([inPLA.sub.2]) act as key enzymes in cell membrane repair and remodeling and in neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes, and neuroinflammation. Box Several cytokine abnormalities are found in schizophrenia Evidence of abnormal concentrations of cytokines in people with schizophrenia is robust and revealing: * In a meta-analysis of 62 studies, people with schizophrenia had increased levels of interleukin (IL)-1 receptor antagonist, soluble IL-2 receptor (sIL-2R), and IL-6; conversely, IL-2 were decreased, relative to controls. (1) * In another meta-analysis of 40 studies, (2) sIL-2R, IL-12 and tumor necrosis factor-a were trait markers of schizophrenia. * The serum IL-6 level was significantly higher in 151 participants with schizophrenia compared with 194 controls; a higher concentration of IL-6 correlated positively with greater cognitive impairments. (3) * An elevated concentration of C-reactive protein (CRP) and exposure to herpes simplex virus type 1 were associated with the severity of cognitive impairments in 588 people with schizophrenia (4); likewise, in a study of 413 participants with schizophrenia, an elevated concentration of CRP was associated with the severity of cognitive impairments. (5) * An elevated IL-2 concentration correlated positively with scores on the digit span test of cognitive status in 29 medicated outpatients with schizophrenia. (6) * In a meta-analysis of 8 studies, the CRP concentration was significantly elevated in people with schizophrenia compared with controls (effect size = 0.45; P In a study, people with first-episode schizophrenia (n = 24) who were drug-naive or off antipsychotic medication were compared with 25 healthy controls using voxel-based morphometry analysis of T, high-resolution MRI. …