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      The Effects of Antipsychotic Treatment on the Brain of Patients With First-Episode Schizophrenia: A Selective Review of Longitudinal MRI Studies

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          Abstract

          A large number of neuroimaging studies have detected brain abnormalities in first-episode schizophrenia both before and after treatment, but it remains unclear how these abnormalities reflect the effects of antipsychotic treatment on the brain. To summarize the findings in this regard and provide potential directions for future work, we reviewed longitudinal structural and functional imaging studies in patients with first-episode schizophrenia before and after antipsychotic treatment. A total of 36 neuroimaging studies was included, involving 21 structural imaging studies and 15 functional imaging studies. Both anatomical and functional brain changes in patients after treatment were consistently observed in the frontal and temporal lobes, basal ganglia, limbic system and several key components within the default mode network (DMN). Alterations in these regions were affected by factors such as antipsychotic type, course of treatment, and duration of untreated psychosis (DUP). Over all we showed that: (a) The striatum and DMN were core target regions of treatment in schizophrenia, and their changes were related to different antipsychotics; (b) The gray matter of frontal and temporal lobes tended to reduce after long-term treatment; and (c) Longer DUP was accompanied with faster hippocampal atrophy after initial treatment, which was also associated with poorer outcome. These findings are in accordance with previous notions but should be interpreted with caution. Future studies are needed to clarify the effects of different antipsychotics in multiple conditions and to identify imaging or other biomarkers that may predict antipsychotic treatment response. With such progress, it may help choose effective pharmacological interventional strategies for individuals experiencing recent-onset schizophrenia.

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          Most cited references76

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          Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.

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            Searching for a baseline: functional imaging and the resting human brain.

            Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.
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              Schizophrenia

              Summary Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome whose origins appear to lie in genetic and/or environmental disruption of brain development. Dysfunction of dopaminergic neurotransmission appears to contribute to the genesis of psychotic symptoms but the evidence also points to a more widespread and variable involvement of brain areas and circuits. There is emerging evidence that disturbances of synaptic function might underlie abnormalities of neuronal connectivity possibly involving interneurons, but the precise nature, location and timing of these events is uncertain. Current treatment consists largely in the administration of antipsychotic drugs combined with psychological therapies, social support and rehabilitation, but there is a pressing need for more effective treatments and for services to be delivered more effectively. Progress in understanding the disorder has been great in recent years with advances in genomics, epidemiology and neuroscience, and the opportunities for further scientific advance are great: but so are the challenges.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                24 June 2021
                2021
                : 12
                : 593703
                Affiliations
                [1] 1Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University , Chengdu, China
                [2] 2Department of Radiology, West China Hospital, Sichuan University , Chengdu, China
                [3] 3Functional and Molecular Imaging Key Laboratory of Sichuan Province, Psychoradiology Research Unit, Chinese Academy of Medical Sciences, West China Hospital, Sichuan University , Chengdu, China
                [4] 4Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research , Manhasset, NY, United States
                [5] 5Division of Psychiatry Research, Zucker Hillside Hospital , Glen Oaks, NY, United States
                Author notes

                Edited by: Stefan Borgwardt, University of Basel, Switzerland

                Reviewed by: Cristina Crocamo, University of Milano Bicocca, Italy; Long-Biao Cui, People's Liberation Army General Hospital, China

                *Correspondence: Wenjing Zhang wjzhang19@ 123456scu.edu.cn

                This article was submitted to Schizophrenia, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work

                Article
                10.3389/fpsyt.2021.593703
                8264251
                34248691
                31c956ad-c91e-40e8-a5f3-929d18ac39a0
                Copyright © 2021 Yang, Tang, Liu, Yao, Xu, Sun, Tao, Gong, Cao, Zhang and Lui.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 August 2020
                : 28 May 2021
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 76, Pages: 9, Words: 7163
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81621003
                Award ID: 82071908
                Funded by: Fundamental Research Funds for the Central Universities 10.13039/501100012226
                Award ID: 2020SCU12053
                Funded by: Sichuan Province Science and Technology Support Program 10.13039/100012542
                Award ID: 2020YJ0018
                Award ID: 2021JDTD0002
                Award ID: 2021YFS0077
                Categories
                Psychiatry
                Mini Review

                Clinical Psychology & Psychiatry
                first-episode schizophrenia,antipsychotics,treatment response,longitudinal,magnetic resonance imaging

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