146. Glutamatergic Neurotransmission Modulates Cortico-Striatal Reward Networks Differentially for Treatment-Resistant and Treatment-Responsive Schizophrenia Patients: Evidence from a Multimodal fMRI and 1H-MRS Study

Abstract

associated with this fused jICA component were markedly reduced in SZ relative to HC (P.2. For mean investment, compared to controls, responsive patients showed decreased investment T(39) = 2.6, P.5. Whole-brain analysis of the fMRI data showed that compared to controls, responsive patients showed decreased activation in the right anterior caudate, while resistant patients showed decreased activa-tion in the lingual gyrus and right insular cortex. No differences were found between healthy controls and resistant patients in the caudate. Caudate function and Glu/Cre levels correlated significantly in responsive patients, R = −.41, P < .05, but not resistant patients or healthy controls, P > .2. For the repayment phase, compared to controls, both patient groups showed activation reductions in the anterior cingulate, left precentral gyrus and right medial frontal gyrus. Resistant patients showed significantly increased medial prefrontal activation compared to responsive, which correlated sig-nificantly with Glu/Cre in resistant patients, R = −.47, P < .05, but not in responsive patients or healthy controls, P > .15. Conclusion: We show for the first time that for similar behavioral deficits, resistant and responsive patients show the engagement of different neural systems associated with social cognition and reward. Crucially, glutamater-gic neurotransmision modulates differentially the corticostriatal network for the 2 groups. This indicates that dissociable neurochemical circuitry and differential dopamine and glutamate interactions in reward processing might underlie antipsychotic treatment-resistance. The elucidation of these differences is crucial for informing novel treatments.