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Changes in Brain Structure, Function, and Network Properties in Patients With First-Episode Schizophrenia Treated With Antipsychotics.

ABSTRACT: Purpose: Comprehensive and longitudinal brain analysis is of great significance for understanding the pathological changes of antipsychotic drug treatment in patients with schizophrenia. This study aimed to investigate the changes of structure, function, and network properties in patients with first-episode schizophrenia (FES) after antipsychotic therapy and their relationship with clinical symptoms. Materials and Methods: A total of 30 patients diagnosed with FES and 30 healthy subjects matched for sex and age were enrolled in our study. Patients at baseline were labeled as antipsychotic-naive first-episode schizophrenia (AN-FES), and patients after antipsychotic treatment were labeled as antipsychotic treatment first-episode schizophrenia (AT-FES). The severity of illness was measured by using the PANSS and CGI score. Structural and functional MRI data were also performed. Differences in GMV, ALFF, and ReHo between the FES group and healthy control group were tested using a voxel-wise two-sample t-test, and the comparison of AN-FES group and AT-FES group was evaluated by paired-sample t-test. Results: After the 1-year follow-up, the FES patients showed increased GMV in the right cerebellum, right inferior temporal gyrus, left middle frontal gyrus, parahippocampal gyrus, bilateral inferior parietal lobule, and reduced GMV in the left occipital lobe, gyrus rectus, right orbital frontal cortex. The patients also showed increased ALFF in the medial superior frontal gyrus and right precentral gyrus. For network properties, the patients showed reduced characteristic path length and increased global efficiency. The GMV of the right inferior parietal lobule was negatively correlated with the clinical symptoms. Conclusions: Our study showed that the antipsychotic treatment contributed to the structural alteration and functional improvement, and the GMV alteration may be associated with the improvement of clinical symptoms.

SUBMITTER: Yin P

PROVIDER: S-EPMC8668948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceRecent data suggest that treatment with antipsychotics is associated with reductions in cortical gray matter in patients with schizophrenia. These findings have led to concerns about the effect of antipsychotic treatment on brain structure and function; however, no studies to date have measured cortical function directly in individuals with schizophrenia and shown antipsychotic-related reductions of gray matter.ObjectiveTo examine the effects of antipsychotics on brain structure and function in patients with first-episode schizophrenia, using cortical thickness measurements and administration of the AX version of the Continuous Performance Task (AX-CPT) during event-related functional magnetic resonance imaging.Design, setting, and participantsThis case-control cross-sectional study was conducted at the Imaging Research Center of the University of California, Davis, from November 2004 through July 2012. Participants were recruited on admission into the Early Diagnosis and Preventive Treatment Clinic, an outpatient clinic specializing in first-episode psychosis. Patients with first-episode schizophrenia who received atypical antipsychotics (medicated patient group) (n = 23) and those who received no antipsychotics (unmedicated patient group) (n = 22) and healthy control participants (n = 37) underwent functional magnetic resonance imaging using a 1.5-T scanner.Main outcomes and measuresBehavioral performance was measured by trial accuracy, reaction time, and d'-context score. Voxelwise statistical parametric maps tested differences in functional activity during the AX-CPT, and vertexwise maps of cortical thickness tested differences in cortical thickness across the whole brain.ResultsSignificant cortical thinning was identified in the medicated patient group relative to the control group in prefrontal (mean reduction [MR], 0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P = .001), and occipital (MR, 0.24 mm; P = .001) cortices. The unmedicated patient group showed no significant cortical thickness differences from the control group after clusterwise correction. The medicated patient group showed thinner cortex compared with the unmedicated patient group in the dorsolateral prefrontal cortex (DLPFC) (MR, 0.26 mm; P = .001) and temporal cortex (MR, 0.33 mm; P = .047). During the AX-CPT, both patient groups showed reduced DLPFC activity compared with the control group (P = .02 compared with the medicated group and P < .001 compared with the unmedicated group). However, the medicated patient group demonstrated higher DLPFC activation (P = .02) and better behavioral performance (P = .02) than the unmedicated patient group.Conclusions and relevanceThese findings highlight the complex relationship between antipsychotic treatment and the structural, functional, and behavioral deficits repeatedly identified in schizophrenia. Although short-term treatment with antipsychotics was associated with prefrontal cortical thinning, treatment was also associated with better cognitive control and increased prefrontal functional activity. This study adds important context to the growing literature on the effects of antipsychotics on the brain and suggests caution in interpreting neuroanatomical changes as being related to a potentially adverse effect on brain function.

Project description:BackgroundInflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia.MethodsThirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients.ResultsPatients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients.ConclusionsPatients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.

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Changes in Brain Structure, Function, and Network Properties in Patients With First-Episode Schizophrenia Treated With Antipsychotics.

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