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

In our final experiment, we treated animals with pioglitazone and measured various behavioral outputs that are endophenotypes for schizophrenia (55, 56) . First, we assessed locomotor activity, stereotypic behaviors, and mania-like behavior. Next, we assessed executive function and cognitive flexibility using the puzzle-box test. This test requires the mouse to display problem-solving behavior as well as short-and long-term explicit memory to reach a goal area. To assess pioglitazone's effect on sociability, we used an ageand sex-matched mouse as a social stimulus (57) . Finally, we assessed sensorimotor gating using the pre-pulse inhibition (PPI) of acoustic startle paradigm (58) . Taken together, these studies provide a bioinformatics translational approach to identify novel treatment strategies through the use of the LINCS library of signatures and connectivity analysis, coupled with the analyses of primary data and published work (to extend the set of 'seed' genes).