Dysfunction, hypoactivity, and hypometabolism of the prefrontal cortex (PFC) may contribute to the negative symptoms and cognitive deficits of schizophrenia.
1-6 The molecular pathogenesis of prefrontal dysfunction in schizophrenia is still not clear, but the down-regulated expression of a subset of metabolic genes is thought to be involved.
7-9 Alterations in cellular metabolism may then further compromise orderly gene expression, affecting neurotransmission,
10-20 myelination,
10,21,22 and other functions.
23,24 There is evidence that in individual schizophrenic patients, PFC hypometabolism persists for decades,
25 suggesting that the underlying molecular mechanisms, including dysregulated metabolic gene expression, remain stable for extended periods.