Cortical pathology in schizophrenia: a review of data from the dorsolateral prefrontal cortex

Converging evidence from investigations of a structure in the prefrontal cortex, the dorsolateral prefrontal cortex, provides intriguing data showing abnormalities ranging from neuropathological to functional changes in schizophrenia. Brain-imaging studies demonstrate that the dorsolateral prefrontal cortex is critical to working memory. People with schizophrenia have difficulty performing tasks involving working memory, and brain-imaging studies of the dorsolateral prefrontal cortex show that, during test performances, dorsolateral prefrontal cortex activation is less than that of controls. Results of dorsolateral prefrontal cortex brain tissue studies in people with schizophrenia reveal abnormalities that could affect neuronal circuitry function. Preliminary findings with microarray analyses support findings of ‘faulty’ wiring of brain circuitries relevant to dorsolateral prefrontal cortex function. The neurodevelopmental hypothesis of schizophrenia suggests that defects in the dorsolateral prefrontal cortex may result from early errors in brain development due to genetic factors and/or environmental influences (e.g. trauma, viral causes). This paper reviews a convincing body of evidence implicating defects in the dorsolateral prefrontal cortex that might explain the prominent cognitive symptoms observed in schizophrenia.