Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture.
Biol Psychiatry
; 89(3): 308-319, 2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-33357631
BACKGROUND: Despite the marked interindividual variability in the clinical presentation of schizophrenia, the extent to which individual dimensions of psychopathology relate to the functional variability in brain networks among patients remains unclear. Here, we address this question using network-based predictive modeling of individual psychopathology along 4 data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns. METHODS: We investigated resting-state functional magnetic resonance imaging data from 147 patients with schizophrenia recruited at 7 sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using a relevance vector machine based on functional connectivity within 17 meta-analytic task networks following repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of 9 receptors/transporters from prior molecular imaging in healthy populations. RESULTS: Tenfold and leave-one-site-out analyses revealed 5 predictive network-symptom associations. Connectivity within theory of mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory of mind and socioaffective default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D1 receptor and serotonin reuptake transporter densities as well as dopamine synthesis capacity. CONCLUSIONS: We revealed a robust association between intrinsic functional connectivity within networks for socioaffective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, this work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.
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Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article