M23. ALTERATION OF REGIONAL CEREBRAL BLOOD FLOW MEASURED BY ARTERIAL SPIN LABELING IN PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA

BACKGROUND: Approximately 30% of patients with schizophrenia do not respond to antipsychotics, which is called treatment-resistant schizophrenia (TRS). A recent systematic review showed decreased regional cerebral blood flow (rCBF) in the cerebral cortex and increased rCBF in the putamen in patients with schizophrenia. However, to date, no study has examined rCBF using arterial spin labeling (ASL) in patients with TRS. Thus, we compared rCBF between patients with TRS and those with non-TRS to investigate neural basis of this condition. METHODS: We acquired whole-brain rCBF measurements using 1.5T magnetic resonance imaging (MRI) with pseudo-continuous ASL in those with TRS and non-TRS. TRS was defined as 1) a Clinical Global Impression Severity (CGI-S) score of ≧ 4 (moderate) and 2) a score of ≧ 4 (moderate) on two Positive and Negative Syndrome Scale (PANSS) positive symptom items after optimal antipsychotic treatment. Non-TRS was defined as 1) a CGI-S score of ≦3, 2) scores of ≦ 3 on all positive symptom items of the PANSS, and 3) no symptomatic relapse during the previous 3 months. Optimal antipsychotic treatment was defined as ≧ 6 consecutive weeks with ≧ 400 mg of chlorpromazine (CPZ) equivalent daily dose antipsychotic treatment. The rCBF maps were subsequently derived from the proton-density-weighted reference images. Group differences in rCBF between the two groups (non-TRS vs. TRS) were tested using two sample t-test with age, gender, and PANSS positive scores as covariates. Multiple comparisons were corrected using familywise error (FWE) method with a significance threshold of P <.05. RESULTS: A total of 32 participants were included (13 TRS [6 females, age= 41.2±9.8, PANSS=80.3±9.7] and 19 non-TRS [6 females, age= 40.6±11.9, PANSS=58.9±10.0]). rCBF in the cerebellum was increased in the TRS group compared with the non-TRS group. In addition, there are inverse correlation between rCBF in the cerebellum and PANSS positive score in the non-TRS group. DISCUSSION: These preliminary results suggest that perfusion in the cerebellum may be implicated in the pathophysiology of TRS. This study will continue to enroll participants (our target sample is 30/each group). To identify the abnormal rCBF in patients with TRS will facilitate elucidating the pathophysiology of TRS and pave a way of developing novel treatment of this difficult-to-treat population.