Amphetamine-Induced Dopamine Release Predicts 1-Year Outcome in First-Episode Psychosis: A Naturalistic Observation

Ana Weidenauer; Ulrich Sauerzopf; Martin Bauer; Carina Bum; Cornelia Diendorfer; Irena Dajic; Lucie Bartova; Alina Kastner; Karsten Bamminger; Lukas Nics; Cecile Philippe; Marcus Hacker; Dan Rujescu; Wolfgang Wadsak; Nicole Praschak-Rieder; Matthäus Willeit

doi:10.1093/schbul/sbae111

Amphetamine-Induced Dopamine Release Predicts 1-Year Outcome in First-Episode Psychosis: A Naturalistic Observation

Schizophr Bull. 2024 Aug 13:sbae111. doi: 10.1093/schbul/sbae111. Online ahead of print.

Authors

Ana Weidenauer^{1

2

3

4}, Ulrich Sauerzopf^{1

2}, Martin Bauer^{1

2

5

6}, Carina Bum^{1

2}, Cornelia Diendorfer^{1

2}, Irena Dajic^{1

2}, Lucie Bartova^{1

2}, Alina Kastner^{1

2}, Karsten Bamminger⁷, Lukas Nics⁷, Cecile Philippe⁷, Marcus Hacker⁷, Dan Rujescu^{1

2}, Wolfgang Wadsak^{7

8}, Nicole Praschak-Rieder^{1

2}, Matthäus Willeit^{1

2}

Affiliations

¹ Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Vienna, Austria.
² Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
³ Douglas Research Centre, Clinical and Translational Sciences Lab, Montreal, Quebec, Canada.
⁴ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁵ Department of Clinical Pharmacology, Medical University of Vienna, Austria.
⁶ Psychosocial Services in Vienna, Vienna, Austria.
⁷ Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Austria.
⁸ Center for Biomarker Research in Medicine CBmed, Graz, Austria.

PMID: 39137162
DOI: 10.1093/schbul/sbae111

Abstract

Background and hypothesis: The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia.

Study design: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29).

Study results: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits.

Conclusions: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.

Keywords: PET; PHNO; dopamine release; patients; psychosis; schizophrenia; symptoms.

Abstract

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