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

We used laser capture microdissection coupled with quantitative polymerase chain reaction (LCM-qPCR) to assess mRNA expression of our metabolic targets in enriched populations of astrocytes and pyramidal neurons in schizophrenia and control subjects (Table S1 and S2). We have previously shown our LCM samples are enriched for specific cellsubtypes using neurochemical markers (11, 18, 59, 60) . No significant associations were found between pH, post-mortem interval (PMI), RNA integrity number (RIN), or age and any of our dependent measures. In a sample enriched for pyramidal neurons, we found decreases in PFKL (27%, p=0.010) and GPI (26%, p=0.015) mRNA expression (Figure 2 , p<0.05). We did not detect any significant changes in mRNA expression in samples enriched for astrocytes ( Figure S1 ). To assess the use of antipsychotic medication in our patient population, we reanalyzed our significant cell-level targets with and without antipsychotic naïve subjects. All findings remained significant without these subjects (PFKL p=0.037, GPI p=0.034) ( Figure S2 , panels A and B).