A neuroimaging biomarker for striatal dysfunction in schizophrenia
- 23 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 26 (4), 558-565
- https://doi.org/10.1038/s41591-020-0793-8
Abstract
Mounting evidence suggests that function and connectivity of the striatum is disrupted in schizophrenia1,2,3,4,5. We have developed a new hypothesis-driven neuroimaging biomarker for schizophrenia identification, prognosis and subtyping based on functional striatal abnormalities (FSA). FSA scores provide a personalized index of striatal dysfunction, ranging from normal to highly pathological. Using inter-site cross-validation on functional magnetic resonance images acquired from seven independent scanners (n = 1,100), FSA distinguished individuals with schizophrenia from healthy controls with an accuracy exceeding 80% (sensitivity, 79.3%; specificity, 81.5%). In two longitudinal cohorts, inter-individual variation in baseline FSA scores was significantly associated with antipsychotic treatment response. FSA revealed a spectrum of severity in striatal dysfunction across neuropsychiatric disorders, where dysfunction was most severe in schizophrenia, milder in bipolar disorder, and indistinguishable from healthy individuals in depression, obsessive-compulsive disorder and attention-deficit hyperactivity disorder. Loci of striatal hyperactivity recapitulated the spatial distribution of dopaminergic function and the expression profiles of polygenic risk for schizophrenia. In conclusion, we have developed a new biomarker to index striatal dysfunction and established its utility in predicting antipsychotic treatment response, clinical stratification and elucidating striatal dysfunction in neuropsychiatric disorders.This publication has 60 references indexed in Scilit:
- Genetic relationship between five psychiatric disorders estimated from genome-wide SNPsNature Genetics, 2013
- Striatal Dopamine Transporter Availability in Drug-Naive Patients With Schizophrenia: A Case-Control SPECT Study With [99mTc]-TRODAT-1 and a Meta-AnalysisSchizophrenia Bulletin, 2011
- Functional Network Organization of the Human BrainNeuron, 2011
- Antipsychotic Drugs Rapidly Induce Dopamine Neuron Depolarization Block in a Developmental Rat Model of SchizophreniaJournal of Neuroscience, 2011
- Decoding Subject-Driven Cognitive States with Whole-Brain Connectivity PatternsCerebral Cortex, 2011
- Neural basis of global resting-state fMRI activityProceedings of the National Academy of Sciences of the United States of America, 2010
- Longitudinal Analysis of Neural Network Development in Preterm InfantsCerebral Cortex, 2010
- SchizophreniaThe Lancet, 2009
- The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common PathwaySchizophrenia Bulletin, 2009
- Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based studyThe Lancet, 2009