S87. ALTERED BRAIN MACROMOLECULES IN SCHIZOPHRENIA: A 1H MRS STUDY

Inflammatory processes are thought to play a role in the pathophysiology of schizophrenia (SZ). Macromolecules are signals from proteins, lipids, and nucleic acids thought to reside in the cytosol and are elevated in multiple sclerosis and stroke in humans as well as with microglia activation in rodent models. Peripheral lipopolysaccharide (LPS) administration to induce inflammation in rodents causes an increase in macromolecule MM09 that corresponds with microglia activation/changes. Brain macromolecules can be measured with specialized magnetic resonance spectroscopy techniques but has never been examined in schizophrenia. The purpose of this ongoing study is to investigate if macromolecule signals from several brain regions are different in patients with SZ compared to controls and if macromolecules are related to psychopathology and a peripheral marker of inflammation, CRP. 13 adults with SZ and 13 healthy controls (HC) participated in this study. Neuropsychological assessments (MATRICS) and psychiatric symptom ratings (BPRS, SANS) were administered. All participants were scanned on a 3T Siemens Prisma MR system using a 64-channel phased array head coil. Macromolecule (MM) data were acquired using a very short TE metabolite-nulled sequence: TR/TE/TM: 2000/6.5/10 ms, 2048 complex points, 2500 kHz spectral width, and 16-step phase cycling. Voxels were placed in the anterior cingulate (VOI=9 cm3, NEX=128), white matter (VOI = 6.75cm3, NEX=256), and striatum (VOI=8cm3, NEX=256). A water reference (NEX=16) was acquired for referencing. Based on previous work by Snoussi et al (2015), a basis set of Gaussian peaks corresponding to macromolecule resonances at 0.9 (MM09), 1.2 (MM12), 1.4 (MM14), 1.7 (MM17), 2.0 (MM20), 2.3 (MM23), and 3.0 (MM30) ppm was imported into TARQUIN and used for spectral fitting. One-way ANOVAs were performed to test for group differences (α=0.05/3), and correlation analyses were performed to examine the relationship between macromolecule levels, clinical symptoms, and cognitive measures (α=0.05/3). White matter MM20, MM23, and MM30 and anterior cingulate MM23 were higher in SZ compared to HC at a trend levels (p=0.03–0.97). More severe psychopathology was related to higher levels of MM09, MM12, MM17, and MM23. BPRS total scores were positively related to MM09, MM12, and MM23 in the striatum at trend level (p=0.034–0.43), and BPRS positive scores were significantly and positively related to striatum MM17 (p=0.011) and white matter MM09 (p=0.014) as well as white matter MM23 (p=0.044) at trend level. SANS scores were positively and significantly related to striatum MM17 (p=0.006) and trend level related to MM09 (p=0.076). This study shows for the first time that brain macromolecules are higher in adults with SZ in several brain regions. Further, higher levels of macromolecules are associated with more significant symptom severity. Because of the differences in MM levels, this data suggests that typical magnetic resonance spectroscopy quantification strategies that utilize a universal basis set for macromolecules may not be capturing important information about SZ. Thus, this data highlights the importance brain macromolecules in SZ and its potential as a biomarker for clinical symptoms.