Left dorsolateral prefrontal cortex dysfunction in medication-naive schizophrenia.

Abnormalities in the frontal lobe are considered to be central to the pathology of schizophrenia. Neuroimaging studies indeed report abnormal function of the frontal lobe in schizophrenia patients. However, the nature of these functional abnormalities is unclear, in particular whether they are affected by medication. We therefore investigated whether frontal functioning is already abnormal in first-episode medication-naive schizophrenia, and if so, if this dysfunction is related to symptomatology. Thirty medication-naive male patients with first-episode schizophrenia and 36 matched healthy controls performed a modified working memory task while fMRI data were acquired. During the task, subjects were presented with novel task (NT) and practiced task (PT) memory sets. Compared to controls, patients showed reduced performance during NT and PT. However, both groups performed better during PT, indicating that practice improved performance. Importantly, practice reduced brain activation in both patients and controls, but this effect of practice was significantly smaller in patients compared to controls, specifically in the left dorsolateral prefrontal cortex (DLPFC; p=0.01). The reduced effect of practice on brain activation was related to the severity of negative symptoms and disorganization. These results suggest that DLPFC function is deficient in the early phases of schizophrenia and cannot be attributed to the use of antipsychotics.