One prominent theory proposes that these deficits and symptoms arise from dysfunctional receptors for the major excitatory neurotransmitter in the brain, glutamate (3), in two different ways. First, it is believed that decreased signaling from glutamate receptors on inhibitory neurons leads to excessive glutamate activity in the prefrontal cortex, resulting in cognitive impairment (2). This decreased signaling from glutamate receptors may result from too little glutamate present at receptors with mGlu2/3 subunits on inhibitory neurons. In a second mechanism, excessive oxidizing species surrounding glutamate receptors in schizophrenia cause receptor hypofunction (2). Glutathione, the most important protective molecule against oxidative stress in the brain, is protective against this. Importantly, glutathione was found to be 52% lower in medial prefrontal cortex of schizophrenia patients compared to controls (4). In rats, inhibition of glutathione synthesis produced cognitive deficits, and a recent study showed an inverse correlation between glutathione and negative symptoms in patients (5,6). Remarkably, there is an agent that affects both glutamate and glutathione: the dietary supplement N-acetylcysteine, or NAC.