Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.
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ABSTRACT:
SUBMITTER: Lei W
PROVIDER: S-EPMC4519942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Schizophrenia is a complex disorder associated with aberrant brain functional connectivity. This study aims to demonstrate the relation of heterogeneous symptomatology in this disorder to distinct brain connectivity patterns within the triple-network model. The study sample comprised 300 first-episode antipsychotic-naive patients with schizophrenia (FES) and 301 healthy controls (HCs). At baseline, resting-state functional magnetic resonance imaging data were captured for each participant, and concomitant neurocognitive functions were evaluated outside the scanner. Clinical information of 49 FES in the discovery dataset were reevaluated at a 6-week follow-up. Differential features between FES and HCs were selected from triple-network connectivity profiles. Cutting-edge unsupervised machine learning algorithms were used to define patient subtypes. Clinical and cognitive variables were compared between patient subgroups. Two FES subgroups with differing triple-network connectivity profiles were identified in the discovery dataset and confirmed in an independent hold-out cohort. One patient subgroup appearing to have more severe clinical symptoms was distinguished by salience network (SN)-centered hypoconnectivity, which was associated with greater impairments in sustained attention. The other subgroup exhibited hyperconnectivity and manifested greater deficits in cognitive flexibility. The SN-centered hypoconnectivity subgroup had more persistent negative symptoms at the 6-week follow-up than the hyperconnectivity subgroup. The present study illustrates that clinically relevant cognitive subtypes of schizophrenia may be associated with distinct differences in connectivity in the triple-network model. This categorization may foster further analysis of the effects of therapy on these network connectivity patterns, which may help to guide therapeutic choices to effectively reach personalized treatment goals.
| S-EPMC8208970 | biostudies-literature
Project description:Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.
| S-EPMC6811827 | biostudies-literature
Project description:BackgroundGrey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.Methods343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying 'networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.ResultsCompared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.ConclusionsIn untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.
| S-EPMC10277763 | biostudies-literature
Project description:BackgroundData on differences in brain features between monozygotic (MZ) twins with and without schizophrenia are scarce.MethodsWe compared brain features of female MZ twins with and without first-episode schizophrenia and healthy controls (n = 20 each). Voxel-based morphometry and tract-based spatial statistics were used to analyze differences in brain structure. Whole-brain effective connectivity (EC) and functional connectivity (FC) networks were constructed using resting-state functional magnetic resonance imaging (rs-fMRI) data.ResultsFemale twins with schizophrenia exhibited abnormal gray matter volume (GMV) in the basal ganglia and prefrontal and parietal cortices, impairments in the arcuate fasciculus, and significant disruptions (primarily decreases) in nine EC networks. They exhibited rs-EC alterations involving the limbic areas and subcortex. Combined rs-EC and rs-FC data distinguished twins with first-episode schizophrenia with high accuracy. Combined consideration of structural and functional features enabled the distinction of female MZ twins with schizophrenia from those without schizophrenia and healthy controls with 100% accuracy.ConclusionsFemale MZ twins with schizophrenia exhibited increased GMV, white matter impairment, and disruptions in EC and FC networks. The combination of rs-EC + rs-FC data could distinguish female twins with schizophrenia from twins without schizophrenia and healthy controls with 97.4% accuracy, and the addition of structural brain features yielded a 100% accuracy rate. These findings may provide pivotal insight for further study of the mechanisms underlying schizophrenia.
| S-EPMC7882158 | biostudies-literature
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:Neural substrates behind schizophrenia (SZ) and its heritability mediated by brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of activation in the brain, reflects the neuronal metabolism, and is promisingly used to detect cerebral alteration thereby shedding light on the features of individuals at high genetic risk. We performed a cross-sectional functional magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naïve patients with SZ, 32 unaffected first-degree relatives of these patients, and 51 healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological properties. SZ patients showed increased CBF in the left medial superior frontal gyrus and right precuneus compared with HCs, and decreased CBF in the left middle temporal gyrus compared with their relatives. Furthermore, unaffected relatives revealed higher level of CBF pronounced in regions within default mode network (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns. Notably, as for the network properties, unaffected relatives were with an intermediate level between SZ patients and HCs in the local efficiency and global efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the CBF connectivity pattern might be a familial feature in the brain of first-episode SZ patients and their relatives.
| S-EPMC5700958 | biostudies-literature
Project description:BackgroundSchizophrenia (SZ) is associated with the highest disability rate among serious mental disorders. Excited symptoms are the core symptoms of SZ, which appear in the early stage, followed by other stages of the disease subsequently. These symptoms are destructive and more prone to violent attacks, posing a serious economic burden to the society. Abnormal spontaneous activity in the orbitofrontal cortex had been reported to be associated with excited symptoms in patients with SZ. However, whether the abnormality appears in first-episode drug-naïve patients with SZ has still remained elusive.MethodsA total of 56 first-episode drug-naïve patients with SZ and 27 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) and positive and negative syndrome scale (PANSS). First, differences in fractional amplitude of low-frequency fluctuations (fALFF) between first-episode drug-naïve patients with SZ and healthy controls were examined to identify cerebral regions exhibiting abnormal local spontaneous activity. Based on the fALFF results, the resting-state functional connectivity analysis was performed to determine changes in cerebral regions exhibiting abnormal local spontaneous activity. Finally, the correlation between abnormal functional connectivity and exciting symptoms was analyzed.ResultsCompared with the healthy controls, first-episode drug-naïve patients with SZ showed a significant decrease in intrinsic activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and the left orbitofrontal cortex. In addition, first-episode drug-naïve patients with SZ had significantly reduced functional connectivity values between the left orbitofrontal cortex and several cerebral regions, which were mainly distributed in the bilateral postcentral gyrus, the right middle frontal gyrus, bilateral paracentral lobules, the left precentral gyrus, and the right median cingulate. Further analyses showed that the functional connectivity between the left orbitofrontal cortex and the left postcentral gyrus, as well as bilateral paracentral lobules, was negatively correlated with excited symptoms in first-episode drug-naïve patients with SZ.ConclusionOur results indicated the important role of the left orbitofrontal cortex in first-episode drug-naïve patients with SZ and suggested that the abnormal spontaneous activity of the orbitofrontal cortex may be valuable to predict the occurrence of excited symptoms. These results may provide a new direction to explore the excited symptoms of SZ.
| S-EPMC9366470 | biostudies-literature
Project description:Background:The investigation of large-scale intrinsic connectivity networks in antipsychotic-naïve first-episode schizophrenia increases our understanding of system-level cerebral dysfunction in schizophrenia while enabling control of confounding effects of medication and disease progression. Reports on functional connectivity in antipsychotic-naïve patients have been mixed and the relation between network alterations, psychopathology and cognition is unclear. Methods:A total number of 47 patients with first-episode schizophrenia who had never received antipsychotic medication and 47 healthy controls were scanned with functional magnetic resonance imaging under resting conditions. Main outcome measures were differences in functional connectivity between groups and the relationship between network alterations, psychopathology and cognition. Results:Altered connectivity was found between right central executive network (CEN) and right ventral attention network (VAN) (patients > controls, P = .001), left CEN and left VAN (P = .002), and between posterior default mode network and auditory network (P = .006). Association between network connectivity and clinical characteristics was found as interactions between the effects of group and sustained attention (P = .005) and between group and processing speed (P = .007) on the connectivity between right CEN and right VAN. Conclusions:Our findings suggest that the early phase of schizophrenia is characterized by increased connectivity between fronto-parietal networks suggested to be involved in the control of cognitive and sensory functions. Moreover, the present study suggests that the problem of not disengaging the VAN leads to difficulties with attention and possibly subjective awareness.
| S-EPMC6192505 | 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:Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first-episode treatment-naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal-temporal association cortex, but reduced myelination of the cingulo-insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ.
| S-EPMC7294057 | biostudies-literature