Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of d-cycloserine

The objective of the present study was to examine patterns of cortical activation underlying d-cycloserine's therapeutic efficacy in schizophrenic patients using functional magnetic resonance imaging (fMRI). We measured frontal and temporal lobe activation following a word fluency task in 12 subjects meeting DSM-IV criteria for schizophrenia at baseline and after 8 weeks of supervised treatment, using a double-blind, placebo-controlled design. Half of the patients received d-cycloserine (n=6) as a supplement to their conventional neuroleptic treatment while the other half (n=6) was augmented with placebo. Patients receiving d-cycloserine, but not placebo, demonstrated a significant increase in temporal lobe activation. This increased activation was significantly associated with a reduction in negative symptoms. These results suggest that the addition of d-cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function.