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. 2023 Oct;53(14):6691-6701.
doi: 10.1017/S0033291723000144. Epub 2023 Feb 9.

Cerebral blood flow in striatum is increased by partial dopamine agonism in initially antipsychotic-naïve patients with psychosis

Kirsten Borup Bojesen  1 , Birte Yding Glenthøj  1   2 , Anne Korning Sigvard  1   2 , Karen Tangmose  1   2 , Jayachandra Mitta Raghava  1   3 , Bjørn Hylsebeck Ebdrup  1   2 , Egill Rostrup  1
Affiliations

Cerebral blood flow in striatum is increased by partial dopamine agonism in initially antipsychotic-naïve patients with psychosis

Kirsten Borup Bojesen et al. Psychol Med. 2023 Oct.

Abstract

Background: Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement.

Methods: We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale.

Results: Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome.

Conclusions: The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.

Keywords: Antipsychotic treatment; antipsychotic-naïve; aripiprazole; cerebral blood flow; first-episode psychosis; first-episode schizophrenia; partial dopamine agonist; perfusion.

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Conflict of interest statement

Drs KB Bojesen and K Tangmose received lecture fees from Lundbeck Pharma A/S.

Dr Glenthøj has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) (January 2009 – December 2021), which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose.

Dr BH. Ebdrup received lecture fees and/or is part of the advisory board at Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia AB, Takeda Pharmaceutical Company, Boehringer Ingelheim, and Lundbeck Pharma A/S.

The rest of the authors have no conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
Figure 1 shows mean resting cerebral blood flow (rCBF) in mL/100 g/min in striatum (a) and thalamus (c) in first-episode patients (black line) before and after six weeks of monotherapy with a partial dopamine agonist compared with healthy controls (gray line) as well as rCBF in female patients (black line) compared with male patients (black dashed line) in striatum (b) and thalamus (d). A: Striatal rCBF was affected by treatment in patients (group × time: p = 0.020) due to significantly higher rCBF in first-episode patients after treatment compared with healthy controls. B: Striatal rCBF was significantly lower in female patients compared with male patients at baseline. C: Thalamic rCBF was affected at trendlevel (group × time: p = 0.040) but did not differ significantly between patients and healthy controls at baseline or after treatment. D: Thalamic rCBF did not differ significantly between female and male patients. Vertical bars represent standard error of the mean. *: p < 0.025 (adjusted for two regions). Abbreviations: FEP, first-episode patients with psychosis; HC, Healthy controls.
Fig. 2.
Fig. 2.
Figure 2 shows increased perfusion in putamen in initially antipsychotic-naïve patients with psychosis after six weeks monotherapy with aripiprazole as compared with healthy controls (p < 0.05 based on permutation-based analysis corrected for multiple comparisons) in a voxel-wise analysis, where white matter was masked. The red color illustrates the significance level p < 0.05.
See this image and copyright information in PMC

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