In conclusion, the work done in the Clinical Brain Disorders Branch in the last eight years has provided rich evidence demonstrating the heuristic value of measurements of NAA with MRSI. Although the functional role of this molecule is still debated (as discussed in detail in other contributions to this symposium proceedings), and likely interacts with several metabolic pathways, clearly its measurement provides information related to brain function. The work described above shows convincingly that NAA in the medial temporal lobe and possibly in the DLPFC is reduced in schizophrenia and that this reduction also predicts alterations in cerebral blood flow measured with PET and fMRI. Moreover, NAA levels are a seemingly heritable trait and covary with variations of the BDNF and GRM3 genes that may contribute to the cognitive dysfUnction that constitutes one of the cardinal features of schizophrenia. The link between intermediate phenotypes at the imaging level and biologic mechanisms provided by the discovery of genes that contribute to schizophrenia risk is a critical step in understanding the pathophysiology of this illness, and measurements of NAA have helped to sort out pieces of this puzzle.

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