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. 2023 Aug;53(11):5235-5245.
doi: 10.1017/S0033291722002288. Epub 2022 Aug 25.

Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response

Pierluigi Selvaggi  1   2 , Sameer Jauhar  3   4 , Vasileia Kotoula  1 , Fiona Pepper  3 , Mattia Veronese  1 , Barbara Santangelo  1 , Fernando Zelaya  1 , Federico E Turkheimer  1 , Mitul A Mehta  1 , Oliver D Howes  3   5   6
Affiliations

Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response

Pierluigi Selvaggi et al. Psychol Med. 2023 Aug.

Abstract

Background: Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response.

Methods: We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14).

Results: There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008).

Conclusions: These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Keywords: Arterial spin labelling; cerebral blood flow; first-episode psychosis; schizophrenia.

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Conflict of interest statement

S. J. has received honoraria for educational talks given for Sunovion. K. C. L. has received funding for educational talks S. J. has given. In the past 3 years M. A. M. has acted as an advisory board member for Lundbeck and Forum Pharmaceuticals. He also received research funding from Lundbeck, Takeda and Johnson & Johnson. Dr Howes is a part-time employee of Lundbeck and has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Angelini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Mylan, Neurocrine, Otsuka, Sunovion, Rand, Recordati and Roche. Dr Howes has a patent for the use of dopaminergic imaging. No other conflict of interested are disclosed.

Figures

Fig. 1.
Fig. 1.
Absolute CBF in the selected a priori ROIs. There were significant main effects of group and ROI, and a significant group*ROI interaction (p = 0.032, Greenhouse-Geisser correction). Post-hoc testing showed that CBF was significantly lower in the frontal cortex (Cohen's d = 0.84, p = 0.009) but not the other regions in patients with FEP relative to controls. FEP = first episode psychosis, HC = healthy controls. Asterisks (*) indicated significant tests. Bars indicate 95% confidence intervals.
Fig. 2.
Fig. 2.
Brain sections showing significantly lower absolute CBF in FEP relative to HC in frontal, parietal and occipital cortex (TFCE corrected clusters). Colorbar indicates t-statistics.
Fig. 3.
Fig. 3.
Scatterplots showing significant correlations between relative-to-global frontal CBF at baseline and percentage improvement in total PANSS with subsequent treatment (r = 0.57, p = 0.05).
See this image and copyright information in PMC

References

    1. Agid, O., Kapur, S., Arenovich, T., & Zipursky, R. B. (2003). Delayed-onset hypothesis of antipsychotic action: A hypothesis tested and rejected. Archives of General Psychiatry, 60(12), 1228–1235. doi:10.1001/archpsyc.60.12.1228. - DOI - PubMed
    1. Allen, P., Azis, M., Modinos, G., Bossong, M. G., Bonoldi, I., Samson, C., … McGuire, P. (2018). Increased resting hippocampal and basal ganglia perfusion in people at ultra high risk for psychosis: Replication in a second cohort. Schizophrenia Bulletin, 44(6), 1323–1331. doi:10.1093/schbul/sbx169. - DOI - PMC - PubMed
    1. Allen, P., Chaddock, C. A., Egerton, A., Howes, O. D., Bonoldi, I., Zelaya, F., … McGuire, P. (2016). Resting hyperperfusion of the hippocampus, midbrain, and basal ganglia in people at high risk for psychosis. The American Journal of Psychiatry, 173(4), 392–399. doi:10.1176/appi.ajp.2015.15040485. - DOI - PubMed
    1. Alsop, D. C., Detre, J. A., Golay, X., Günther, M., Hendrikse, J., Hernandez-Garcia, L., … Zaharchuk, G. (2015). Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magnetic Resonance in Medicine, 73(1), 102–116. doi:10.1002/mrm.25197. - DOI - PMC - PubMed
    1. Andreasen, N. C., O'Leary, D. S., Flaum, M., Nopoulos, P., Watkins, G. L., Boles Ponto, L. L., & Hichwa, R. D. (1997). Hypofrontality in schizophrenia: Distributed dysfunctional circuits in neuroleptic-naïve patients. The Lancet, 349(9067), 1730–1734. doi:10.1016/s0140-6736(96)08258-x. - DOI - PubMed

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