Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls
Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls
Abstract Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-na?ve first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.
Chopra Sidhant、Nelson Barnaby、Allott Kelly、Graham Jessica、Tahtalian Steven、Yuen Hok P、Harrigan Susy、O?ˉDonoghue Brian、McGorry Patrick、Fornito Alex、Sharma Sujit、Saluja Bharat、Baldwin Lara、Wood Stephen J.、Aquino Kevin、Pozaruk Andrii、Chen Zhaolin、Alvarez-Jimenez Mario、Pantelis Christos、Cropley Vanessa、Williams Robert、Tran Nancy、Finlay Amy、Sabaroedin Kristina、Razi Adeel、Francey Shona
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash UniversityOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneOrygen, ParkvilleOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneDepartment of Social Work, Monash University||Melbourne School of Population and Global Health, University of MelbourneOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University||Monash Biomedical Imaging, Monash UniversityMonash Health DandenongMonash Health DandenongOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneOrygen, Parkville||Centre for Youth Mental Health, The University of Melbourne||School of Psychology, University BirminghamTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University||Monash Biomedical Imaging, Monash UniversityMonash Biomedical Imaging, Monash UniversityMonash Biomedical Imaging, Monash UniversityOrygen, Parkville||Centre for Youth Mental Health, The University of MelbourneMelbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health||The Florey Institute for Neuroscience and Mental Health, University of MelbourneMelbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne HealthThe University of MelbourneTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash UniversityTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash UniversityTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash UniversityTurner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University||Monash Biomedical Imaging, Monash University||Wellcome Centre for Human Neuroimaging, University College LondonOrygen, Parkville||Centre for Youth Mental Health, The University of Melbourne
神经病学、精神病学基础医学医学研究方法
Chopra Sidhant,Nelson Barnaby,Allott Kelly,Graham Jessica,Tahtalian Steven,Yuen Hok P,Harrigan Susy,O?ˉDonoghue Brian,McGorry Patrick,Fornito Alex,Sharma Sujit,Saluja Bharat,Baldwin Lara,Wood Stephen J.,Aquino Kevin,Pozaruk Andrii,Chen Zhaolin,Alvarez-Jimenez Mario,Pantelis Christos,Cropley Vanessa,Williams Robert,Tran Nancy,Finlay Amy,Sabaroedin Kristina,Razi Adeel,Francey Shona.Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls[EB/OL].(2025-03-28)[2025-05-29].https://www.medrxiv.org/content/10.1101/2021.03.11.21253426.点此复制
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