T212. LEVELS OF GLUTAMATERGIC NEUROMETABOLITES IN PATIENTS WITH SEVERE TREATMENT-RESISTANT SCHIZOPHRENIA: A PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDY

BACKGROUND: Approximately 30% of patients with schizophrenia do not respond to antipsychotics and are thus considered to have treatment-resistant schizophrenia (TRS). To date, only four studies have examined glutamatergic neurometabolite levels using proton magnetic resonance spectroscopy (1H-MRS) in patients with TRS, collectively suggesting that glutamatergic dysfunction may be implicated in the pathophysiology of TRS. Notably, the TRS patient population in these studies had mild to moderate illness severity, which is not entirely reflective of what is observed in clinical practice. METHODS: In this present work, we compared glutamate+glutamine (Glx) levels in the dorsal anterior cingulate cortex (dACC) and caudate among patients with TRS, patients with non-TRS, and healthy controls (HCs), using 3T 1H-MRS (PRESS, TE=35ms). TRS criteria were defined by severe positive symptoms (i.e. ≥5 on 2 Positive and Negative Syndrome Scale (PANSS) positive symptom items or ≥4 on 3 PANSS positive symptom items) despite standard antipsychotic treatment. RESULTS: A total of 95 participants were included (29 TRS patients [PANSS=111.2±20.4], 33 non-TRS patients [PANSS=49.8±13.7], and 33 HCs). dACC Glx levels were higher in the TRS group versus HCs (group effect: F[2,75]=4.74, p=0.011; TRS vs. HCs: p=0.012). No group differences were identified in the caudate. There were no associations between Glx levels in these regions and clinical severity in either patient group. DISCUSSION: Our results confirm that higher dACC Glx might be related to the pathophysiology underlying TRS, by demonstrating this phenomenon in a TRS patient population reflective of clinical practice.