Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals

Author:

Wengler Kenneth12,Baker Seth C.23,Velikovskaya Anastasia2,Fogelson Alissa2,Girgis Ragy R.12,Reyes-Madrigal Francisco4,Lee Seonjoo125,de la Fuente-Sandoval Camilo4,Ojeil Najate2,Horga Guillermo12

Affiliation:

1. Department of Psychiatry, Columbia University, New York, New York

2. New York State Psychiatric Institute, New York

3. University at Buffalo Jacobs School of Medicine and Biological Sciences, Buffalo, New York

4. Laboratory of Experimental Psychiatry & Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico

5. Department of Biostatistics, Columbia University, New York, New York

Abstract

ImportanceThe link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist.ObjectiveTo replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity.Design, Setting, and ParticipantsThis cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample). The main samples consisted of 42 antipsychotic-free patients with schizophrenia, 53 antipsychotic-free individuals at clinical high risk for psychosis (CHR), and 52 matched healthy controls. An external validation sample consisted of 16 antipsychotic-naive patients with schizophrenia.Main Outcomes and MeasuresNM-MRI contrast within a subregion of the substantia nigra previously linked to psychosis severity (a priori psychosis region of interest [ROI]) and psychosis severity measured using the Positive and Negative Syndrome Scale (PANSS) in schizophrenia and the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR. The cross-validated performance of linear support vector regression to predict psychosis severity across schizophrenia and CHR was assessed, and a final trained model was tested on the external validation sample.ResultsOf the 163 included participants, 76 (46.6%) were female, and the mean (SD) age was 29.2 (10.4) years. In the schizophrenia sample, higher PANSS positive total scores correlated with higher mean NM-MRI contrast in the psychosis ROI (t37 = 2.24, P = .03; partial r = 0.35; 95% CI, 0.05 to 0.55). In the CHR sample, no significant association was found between higher SIPS positive total score and NM-MRI contrast in the psychosis ROI (t48 = −0.55, P = .68; partial r = −0.08; 95% CI, −0.36 to 0.23). The 10-fold cross-validated prediction accuracy of psychosis severity was above chance in held-out test data (mean r = 0.305, P = .01; mean root-mean-square error [RMSE] = 1.001, P = .005). External validation prediction accuracy was also above chance (r = 0.422, P = .046; RMSE = 0.882, P = .047).Conclusions and RelevanceThis study provided a direct ROI-based replication of the in-sample association between NM-MRI contrast and psychosis severity in antipsychotic-free patients with schizophrenia. In turn, it failed to replicate such association in CHR individuals. Most critically, cross-validated machine-learning analyses provided a proof-of-concept demonstration that NM-MRI patterns can be used to predict psychosis severity in new data, suggesting potential for developing clinically useful tools.

Publisher

American Medical Association (AMA)

Subject

Psychiatry and Mental health

Reference67 articles.

1. Schizophrenia, dopamine and the striatum: from biology to symptoms.;McCutcheon;Trends Neurosci,2019

2. Defining the locus of dopaminergic dysfunction in schizophrenia: a meta-analysis and test of the mesolimbic hypothesis.;McCutcheon;Schizophr Bull,2018

3. Increased dopamine transmission in schizophrenia: relationship to illness phases.;Laruelle;Biol Psychiatry,1999

4. Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: a PET study.;Howes;Mol Psychiatry,2011

5. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.;Abi-Dargham;Am J Psychiatry,1998

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