Genetic polymorphisms of BDNF on cognitive functions in drug-naive first episode patients with schizophrenia.
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ABSTRACT:
SUBMITTER: Su X
PROVIDER: S-EPMC8501135 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients.Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC).Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients.Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.
| S-EPMC4333112 | biostudies-literature
Project description:Background: Schizophrenia is a severe mental disease which characterized by positive symptom, negative symptom, general pathology syndrome and cognitive deficits. In recent years, many studies have investigated the relationship between cognitive deficits and clinical characteristics in schizophrenia, but relatively few studies have been performed on first-episode drug-naïve patients. Methods: Eighty seven first-episode drug-naïve schizophrenia patients were assessed for positive symptom, negative symptom, general pathology symptom and cognitive deficits from the Positive and Negative Symptom Scale and MATRICS Consensus Cognitive Battery. Psychotics depression were assessed using the Calgary depressing scale for schizophrenia. The relationship between clinical characteristics and cognitive deficits were assessed using correlation analysis and linear regression analysis. Results: The prevalence of cognitive deficits among the patients in our study was 85.1% (74/87) which was much higher than that in the general population. According to correlation analysis, negative symptom was negatively correlated with speed of processing and social cognition, and general pathology showed a negative correlation with attention/vigilance. In addition, a positive correlation was found between age and speed of processing. No correlation was found between cognitive deficits and positive symptom. Conclusions: This study confirmed that negative symptom is negatively related with some domains of cognitive function in first-episode drug naïve schizophrenia patients. Trail Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).
| S-EPMC7950319 | biostudies-literature
Project description:BackgroundRecent neuroimaging studies revealed dysregulated neurodevelopmental, or/and neurodegenerative trajectories of both structural and functional connections in schizophrenia. However, how the alterations in the brain's structural connectivity lead to dynamic function changes in schizophrenia with age remains poorly understood.MethodsCombining structural magnetic resonance imaging and a network control theory approach, the white matter network controllability metric (average controllability) was mapped from age 16 to 60 years in 175 drug-naïve schizophrenia patients and 155 matched healthy controls.ResultsCompared with controls, the schizophrenia patients demonstrated the lack of age-related decrease on average controllability of default mode network (DMN), as well as the right precuneus (a hub region of DMN), suggesting abnormal maturational development process in schizophrenia. Interestingly, the schizophrenia patients demonstrated an accelerated age-related decline of average controllability in the subcortical network, supporting the neurodegenerative model. In addition, compared with controls, the lack of age-related increase on average controllability of the left inferior parietal gyrus in schizophrenia patients also suggested a different pathway of brain development.ConclusionsBy applying the control theory approach, the present study revealed age-related changes in the ability of white matter pathways to control functional activity states in schizophrenia. The findings supported both the developmental and degenerative hypotheses of schizophrenia, and suggested a particularly high vulnerability of the DMN and subcortical network possibly reflecting an illness-related early marker for the disorder.
| S-EPMC8744281 | biostudies-literature
Project description:Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.
| S-EPMC4266300 | biostudies-literature
Project description:Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major treatment target for antipsychotics, the primary treatments for schizophrenia; however, there are few studies on the functional connectivity (FC) of striatum in drug-naive early-onset schizophrenia (EOS) patients. We examined the FC values of the caudate nucleus and putamen with whole brain by resting-state functional magnetic resonance imaging (RS-fMRI) and the associations with indices of clinical severity. Patients demonstrated abnormal FC between subregions of the putamen and both the visual network (left middle occipital gyrus) and default mode network (bilateral anterior cingulate, left superior frontal, and right middle frontal gyri). Furthermore, FC between dorsorostral putamen and left superior frontal gyrus correlated with both positive symptom subscore and total score on the Positive and Negative Syndrome Scale (PANSS). These findings demonstrate abnormal FC between the striatum and other brain areas even in the early stages of schizophrenia, supporting neurodevelopmental disruption in disease etiology and expression.
| S-EPMC9120884 | biostudies-literature
Project description:BackgroundOur previous study has shown the cingulate cortex abnormalities in first-episode drug naïve (FEDN) schizophrenia patients with comorbid depressive symptoms. However, it remains largely unknown whether antipsychotics may induce morphometric change in cingulate cortex and its relationship with depressive symptoms. The purpose of this study was to further clarify the important role of cingulate cortex in the treatment on depressive symptoms in FEDN schizophrenia patients.MethodIn this study, 42 FEDN schizophrenia patients were assigned into depressed patients group (DP, n = 24) and non-depressed patients group (NDP, n = 18) measured by the 24-item Hamilton Depression Rating Scale (HAMD). Clinical assessments and anatomical images were obtained from all patients before and after 12-week treatment with risperidone.ResultsAlthough risperidone alleviated psychotic symptoms in all patients, depressive symptoms were decreased only in DP. Significant group by time interaction effects were found in the right rostral anterior cingulate cortex (rACC) and other subcortical regions in the left hemisphere. After risperidone treatment, the right rACC were increased in DP. Further, the increasing volume of right rACC was negatively associated with improvement in depressive symptoms.ConclusionThese findings suggested that the abnormality of the rACC is the typical characteristics in schizophrenia with depressive symptoms. It's likely key region contributing to the neural mechanisms underlying the effects of risperidone treatment on depressive symptoms in schizophrenia.
| S-EPMC9922813 | biostudies-literature
Project description:Different patterns of gray matter volume (GMV) abnormalities have been reported between chronic patients with deficit schizophrenia (DS), relative to nondeficit schizophrenia (NDS) patients. However, it is not clear whether these differences are characteristic to the pathophysiology of DS or due to the effects of medications or illness durations. To address this issue, GMV in 88 first-episode, drug-naive patients with schizophrenia (44 DS and 44 NDS), 67 of their first-degree relatives and 84 healthy controls were assessed using voxel- based morphometry (VBM) and compared between groups. Correlations between GMV and clinical symptoms in patients were also assessed. Compared to controls, DS patients displayed more severe GMV reduction in the cerebellar culmen than NDS patients. GMV reduction in culmen was also observed in the first-degree relatives of DS (but not NDS) patients, suggesting possible different genetic risk in DS and NDS. The left insula was significantly smaller in DS patients than both NDS patients and controls, and smaller GMV of this region was associated with more severe negative symptoms in patients. Our results collectively indicate that DS might represent a distinct subtype of schizophrenia from NDS and the GMV change in left insula may be a morphological signature of DS.
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Project description:Convergent evidence has suggested a significant effect of antipsychotic exposure on brain structure and function in patients with schizophrenia, yet the characteristics of favorable treatment outcome remains largely unknown. In this work, we aimed to examine how large-scale brain networks are modulated by antipsychotic treatment, and whether the longitudinal changes could track the improvements of psychopathologic scores. Thirty-four patients with first-episode drug-naïve schizophrenia and 28 matched healthy controls were recruited at baseline from Shanghai Mental Health Center. After 8 weeks of antipsychotic treatment, 24 patients were re-scanned. Through a systematical dynamic functional connectivity (dFC) analysis, we investigated the schizophrenia-related intrinsic alterations of dFC at baseline, followed by a longitudinal study to examine the influence of antipsychotic treatment on these abnormalities by comparing patients at baseline and follow-up. A structural connectivity (SC) association analysis was further carried out to investigate longitudinal anatomical changes that underpin the alterations of dFC. We found a significant symptomatic improvement-related increase in the occurrence of a dFC state characterized by stronger inter-network integration. Furthermore, symptom reduction was correlated with increased FC variability in a unique connectomic signature, particularly in the connections within the default mode network and between the auditory, cognitive control, and cerebellar network to other networks. Additionally, we observed that the SC between the superior frontal gyrus and medial prefrontal cortex was decreased after treatment, suggesting a relaxation of normal constraints on dFC. Taken together, these findings provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network. Moreover, our identified neuroimaging markers tied to the neurobiology of schizophrenia could be used as potential indicators in predicting the treatment outcome of antipsychotics.
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Project description:Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10-8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10-7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10-17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.
| S-EPMC5603592 | biostudies-literature
Project description:Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.
| S-EPMC9279212 | biostudies-literature