M18. REDUCED CORTICAL CEREBRAL BLOOD FLOW IN FIRST EPISODE PSYCHOSIS PATIENTS
Authors: Selvaggi Pierluigi , Jauhar Sameer , Kotoula Vasileia , Pepper Fiona , Veronese Mattia , Santangelo Barbara , Zelaya Fernando , Turkheimer Federico , Mehta Mitul , Howes Oliver 
Published: May 2020

Abstract

Background
Abnormal Cerebral Blood Flow (CBF) has been found in patients with chronic schizophrenia (SCZ), first-episode psychosis patients (FEP) and individuals at clinical high-risk (CHR). In particular, previous studies using Arterial Spin Labelling (ASL) found that SCZ have a global reduction of CBF in the cortex and increased CBF in the basal ganglia, the hippocampus, and the amygdala as compared with controls. To date, only one study investigated CBF using ASL in a small cohort of medicated FEP reporting increased CBF in the striatum and reduced frontal CBF as compared with controls. However, it is still not clear whether these abnormalities are related to antipsychotic treatment or rather they reflect a disease state independent from medication. Critically, clinical and pre-clinical evidence suggests that antipsychotics increase CBF, especially in the basal ganglia through dopamine D2 receptors blockade. Here, we assessed CBF differences between FEP and controls in a larger cohort of unmedicated or minimally treated patients. In addition, we tested the association between CBF abnormalities and clinical features.

Methods
26 FEP (13 medication-free, 9 antipsychotics naïve, 4 minimally treated) and 22 healthy controls (HC) were recruited. FEP and HC were matched for age and gender. Among FEP, 11 had a diagnosis of affective psychosis and 15 of non-affective psychosis. MRI scans were acquired using a GE MR750 3T scanner and a 12-channel head coil. ASL data was acquired using a pseudo-continuous ASL sequence (pCASL). Four control-label pairs were used. Quantification of the CBF data was made using a coil sensitivity map and a proton density image. CBF maps were normalized using non-linear registration and smoothed using a 6 mm full width at half maximum (FWHM) kernel. Grey matter CBF and regional CBF values in each Region of Interest (ROI) were extracted using individual grey matter images and WFU-Pickatlas ROIs with the MarsBar toolbox. Based on previous studies the following ROIs were selected: right and left hippocampus, right and left striatum, right and left frontal cortex. Whole-brain voxel-wise analysis was performed using a non-parametric independent t-test as implemented in FSL randomize (Threshold Free Cluster Enhancement, TFCE, and 5000 permutations). Bonferroni method was used to correct ROI analysis for multiple comparisons (alpha = 0.05, n = 7).

Results
Significantly reduced CBF was found in FEP as compared with controls in total grey matter CBF (p = 0.004). Whole-brain voxel-wise analysis FEP-HC comparison revealed a widespread cortical reduction in large cortical clusters that encompass the occipital, parietal and frontal cortices (pFWE TFCE corrected &lt; 0.05). ROI analysis revealed a significant reduction in CBF in the right frontal cortex (p = 0.002). A nominal significant reduction was also detected in the left frontal cortex (p = 0.014). No statistically significant differences were found in the other ROI considered (all p &gt; 0.1). Sub-analysis after removing minimally treated patients did not change the results. Both global grey matter CBF and right frontal CBF were reduced in both affective and non-affective psychosis as compared with controls (p &lt; 0.05), whereas no differences were detected between the two clinical groups.

Discussion
Our results confirm earlier evidence on reduction of cortical perfusion in FEP. However, in contrast with previous studies, we did not detect any difference in striatal perfusion in our cohort of unmedicated/minimally treated patients. Hence, our results support the hypothesis that alteration in striatal perfusion are likely due to medication. Finally, our results suggest that CBF alterations might have a trans-diagnostic role in the pathophysiology of psychosis.