¹Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, London, United Kingdom, ²Institute of Psychiatry, Psychology & Neuroscience, Department of Neuroimaging, London, United Kingdom, ³Institute of Psychiatry, Psychology & Neuroscience, Department of Psychological Medicine, London, United Kingdom

Background: Differences in regional cerebral blood flow (CBF) have been observed across schizophrenia spectrum disorders¹. Findings in the first episode of psychosis (FEP) demonstrate CBF increases in the striatum over the first six weeks of initial treatment with the partial dopamine agonist antipsychotic aripiprazole⁶. Regional CBF prior to antipsychotic treatment has also been associated with subsequent clinical outcomes in FEP, including a positive association between frontal CBF and improvement in total symptom severity⁵ and a negative association between nucleus accumbens CBF and improvement in positive symptom severity⁶. However, there are few studies in this area using MRI measures of CBF.

Aims & Objectives: To investigate changes in regional CBF during antipsychotic treatment and potential associations with symptom improvement.

Method: CBF data from two cohorts of participants with FEP were combined: the STRATA cohort (n = 34, baseline, 2-weeks, and 6-weeks) and the OPTIMISE cohort (n = 22, baseline and 4-weeks). STRATA participants had received antipsychotics for < 4 weeks at baseline and were treated with various antipsychotic medications over the observation period. In OPTIMISE, participants had received antipsychotics for < 2 weeks at baseline, and all participants received amisulpride over the observation period. Data were extracted from four regions of interest: the anterior cingulate cortex (ACC), striatum, hippocampus and thalamus. Data from the two cohorts were combined using "neuroHarmonize" in Python. Changes in CBF during antipsychotic treatment were estimated using hierarchical linear mixed models (LMMs), with days on antipsychotic treatment (time effect), age (fixed covariate), and chlorpromazine equivalence dose (CPZE, time-varying covariate) added stepwise to the models, with and without accounting for global CBF. Exploratory analyses employed LMMs or linear regressions to examine the relationships between clinical symptoms and changes in CBF or baseline CBF under treatment. All analyses were conducted in Python.

Results: During the follow-up period, symptoms improved from a mean (± s.d.) of 72.31 (± 16.61) to 58.39 (± 12.80) for total symptoms as measured on the PANSS. There were no significant longitudinal changes in CBF during antipsychotic treatment. CBF in both the ACC and thalamus were negatively correlated with positive symptoms, while CBF in the thalamus was negatively correlated with general symptoms; however, these associations did not retain significance after correction for multiple comparisons (both p > 0.0125). Antipsychotic dose was negatively associated with CBF in the ACC (p = 0.022) and positively associated with CBF in the thalamus (p = 0.029). There were no significant relationships between baseline CBF and subsequent symptom improvement during antipsychotic treatment.

Discussion & Conclusions: Across this combined sample of 56 participants with FEP, we did not detect any significant effect of time on regional CBF during antipsychotic treatment or relationships with symptom improvement. Participants in our study were minimally medicated but not antipsychotic-naïve at baseline, and it is possible that antipsychotic effects on CBF had occurred early and prior to the baseline scan. Relationships between regional CBF and symptom improvement may be subtle and difficult to detect in smaller cohorts where participants vary in terms of prior or subsequent antipsychotic exposure.