Glutamate and Cognitive Function in Schizophrenia
Presumably, glutamate deficit leads in turn to the cognitive deficits seen in schizophrenia, but measuring glutamate levels in living patients has been difficult. However, researchers using a more powerful imaging techique (4 Tesla proton spectroscopic imaging) have found that levels of combined glutamate and its precursor, glutamine, are correlated with scores on a battery of cognitive tests. Surprisingly, this relationship was seen only in the schizophrenic subjects and not in the controls; in addition, average levels did not differ between the two groups. These results suggest that some deficiency in utilizing glutamate makes the schizophrenic individual particularly vulnerable to any reduction in glutamate. Biological Psychiatry, Vol 69, 19-27.

Mice Explain Link Between Flu and Schizophrenia
The evidence for a causal link between maternal influenza infection and schizophrenia in the offspring is strong, but the mechanism has not been determined. Researchers at Mount Sinai School of Medicine in New York infected pregnant mice with a mouse-adapted influenza virus, then studied their adult offspring. The mice showed behavioral alterations, including reduced spontaneous locomotion, increased responsiveness to hallucinogens, and diminished antipsychotic-like effect of a glutamate agonist. More importantly, the number and activity of 5-HT_2A serotonin receptors was increased, while mGlu₂ glutamate receptors were downregulated in frontal cortex. Journal of Neuroscience, Vol 31, 1863-1872.

Treating Anxiety
Psychotherapy for anxiety typically involves some form of extinction procedure, such as exposing the individual to anxiety-provoking situations in small doses in a safe environment (e.g., through virtual presentation). But anxiety is very resistant to extinction, and often reappears later, so therapists are turning to neuroscience to enhance their efforts. Because extinction is a form of learning, researchers have focused on pharmacological enhancement of learning during the extinction process. One approach has been to administer D-cycloserine (DCS), which facilitates NMDA receptors. Administering DCS prior to therapy sessions has been effective with obsessive-compulsive disorder, panic disorder, phobias, and social anxiety and Cornell University's college of medicine is beginning trials for the treatment of post-traumatic stress disorder in Iraq War veterans Psychiatric Clinics of North America, Vol 33, 687-699; ClinicalTrials.gov, December 13, 2010. A similar approach involves the stress hormone cortisol, which also affects NMDA receptors and facilitates learning. Subjects with height phobia who were treated with a combination of cortisol injections and exposure therapy (virtual reality simulation of high platforms connected by bridges and elevators), show greater phobia reduction than subjects given a placebo prior to exposure therapy. Proceedings of the National Academy of Sciences, Vol 108, 6621-6625 .

A New Pathway for Depression
Recent years have seen reports that a single dose of ketamine can provide relief from depression beginning in just two hours and lasting up to two weeks. But ketamine, which is typically used as an animal anesthetic, is also the popular club drug known as special K, and its potential for abuse keeps doctors from prescribing it for long term use. Now, neuroscientists at the University of Texas Southwestern Medical Center have discovered why ketamine works and, possibly, opened up a new avenue for treatment. Ketamine blocks the NMDA subtype of glutamate receptors. (Remember that schizophrenia is thought to involve reduced glutamate activity; drugs that activate NMDA receptors alleviate symptoms and ketamine increases their symptoms.) Ketamine has an interesting effect: It doesn't interfere with signal transmission in the glutamate pathway, but it does reduce spontaneous activity, which is involved in regulating the synthesis of the protein eEF2. Increasing eEF2 levels in mice produced an antidepressant action (for example, increasing the time a mouse continued swimming before giving up and simply floating). The researchers think that targeting spontaneous transmission and eEF2 protein synthesis could lead to the development of an effective and safe antidepressant. Nature, June 15, 2011, doi:10.1038/nature10130.