The etiology of schizophrenia remains unclear, while there has been a growing amount of evidence for the neuroinflammation and immunogenetics, which are characterized by an increased serum concentration of several pro-inflammatory cytokines. Despite the fact that microglia comprise only <10% of the total brain cells, microglia respond rapidly to even minor pathological changes in the brain and may contribute directly to the neuronal degeneration by producing various pro-inflammatory cytokines and free radicals. In many aspects, the neuropathology of schizophrenia has recently been reported to be closely associatedwith microglial activation. Previous studies have shown the inhibitory effects of some typical/atypical antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, both of which have recently been known to cause a decrease in neurogenesis as well as white matter abnormalities in the brains of patients with schizophrenia. The microglia hypothesis of schizophrenia may shed new light on the therapeutic strategy for schizophrenia.

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The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high‐affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)‐γ‐induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti‐inflammatory effect on IFN‐γ‐induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)‐α from IFN‐γ‐activated microglia and suppressed the IFN‐γ‐induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN‐γ‐induced microglial activation through the suppression of IFN‐γ‐induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti‐inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.

BACKGROUND AND PURPOSE:Cerebral hemodynamics abnormality in Alzheimer disease (AD) is not fully understood. Our aim was to determine whether regional hypoperfusion due to AD is associated with abnormalities in regional arterial blood volume (rABV) and regional arterial transit time (rATT) as measured by quantitative arterial spin-labeling (ASL) with multiple-delay time sampling.