Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments

Courtney R. Sullivan; Catharine A. Mielnik; Sinead M. O’Donovan; Adam J. Funk; Eduard Bentea; Erica A.K. DePasquale; Zhexing Wen; Vahram Haroutunian; Pavel Katsel; Amy J. Ramsey; Jarek Meller; Robert E. McCullumsmith

There is also accumulating evidence of bioenergetic dysfunction in chronic schizophrenia, which has recently been reviewed and highlights a number of abnormalities associated with glucose metabolism, the lactate shuttle, and bioenergetic coupling (13) . There is also evidence for genetic linkage between enzymes that control glycolysis in schizophrenia including 6phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2) and hexokinase 3 (HK3), suggesting that genetic risk for this illness includes bioenergetic substrates (14) . Interestingly, studies using cell-level techniques have demonstrated complex bioenergetic changes, including decreases in mitochondrial oxidative energy metabolism genes in dentate granule neurons (n=22) and in layer 3 and 5 pyramidal neurons from the DLPFC (n=36 and n=19) (15) (16) (17) .