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1.

Background

Evidence shows that STON2 gene is associated with synaptic function and schizophrenia. This study aims to explore the relationship between two functional polymorphisms (Ser307Pro and Ala851Ser) of STON2 gene and the cortical surface area in first-episode treatment-naïve patients with schizophrenia and healthy controls.

Methodology/Principal Findings

Magnetic resonance imaging of the whole cortical surface area, which was computed by an automated surface-based technique (FreeSurfer), was obtained from 74 first-episode treatment-naïve patients with schizophrenia and 55 healthy controls. Multiple regression analysis was performed to investigate the effect of genotype subgroups on the cortical surface area. A significant genotype-by-diagnosis effect on the cortical surface area was observed. Pro-allele carriers of Ser307Pro polymorphism had larger right inferior temporal surface area than Ser/Ser carriers in the patients with schizophrenia; however, no significant difference was found in the same area in the healthy controls. The Ala851Ser polymorphism of STON2 gene was not significantly associated with the cortical surface area in patients with schizophrenia and healthy controls.

Conclusions/Significance

The present study demonstrated that the functional variant of the STON2 gene could alter cortical surface area on the right inferior temporal and contribute to the pathogenesis of schizophrenia.  相似文献   

2.

Background

The default mode network (DMN) has been linked to a number of mental disorders including schizophrenia. However, the abnormal connectivity of DMN in early onset schizophrenia (EOS) has been rarely reported.

Methods

Independent component analysis (ICA) was used to investigate functional connectivity (FC) of the DMN in 32 first-episode adolescents with EOS and 32 age and gender-matched healthy controls.

Results

Compared to healthy controls, patients with EOS showed increased FC between the medial frontal gyrus and other areas of the DMN. Partial correlation analyses showed that the FC of medial frontal gyrus significantly correlated with PANSS-positive symptoms (partial correlation coefficient  = 0.538, Bonferoni corrected P = 0.018).

Limitations

Although the sample size of participants was comparable with most fMRI studies to date, it was still relatively small. Pediatric brains were registered to the MNI adult brain template. However, possible age-specific differences in spatial normalization that arise from registering pediatric brains to the MNI adult brain template may have little effect on fMRI results.

Conclusion

This study provides evidence for functional abnormalities of DMN in first-episode EOS. These abnormalities could be a source of abnormal introspectively-oriented mental actives.  相似文献   

3.

Background

Although schizophrenia has been associated with abnormalities in brain anatomy, imaging studies have not fully determined the nature and relative contributions of gray matter (GM) and white matter (WM) disturbances underlying these findings. We sought to determine the pattern and distribution of these GM and WM abnormalities. Furthermore, we aimed to clarify the contribution of abnormalities in cortical thickness and cortical surface area to the reduced GM volumes reported in schizophrenia.

Methods

We recruited 76 persons with schizophrenia and 57 healthy controls from the community and obtained measures of cortical and WM surface areas, of local volumes along the brain and WM surfaces, and of cortical thickness.

Results

We detected reduced local volumes in patients along corresponding locations of the brain and WM surfaces in addition to bilateral greater thickness of perisylvian cortices and thinner cortex in the superior frontal and cingulate gyri. Total cortical and WM surface areas were reduced. Patients with worse performance on the serial-position task, a measure of working memory, had a higher burden of WM abnormalities.

Conclusions

Reduced local volumes along the surface of the brain mirrored the locations of abnormalities along the surface of the underlying WM, rather than of abnormalities of cortical thickness. Moreover, anatomical features of white matter, but not cortical thickness, correlated with measures of working memory. We propose that reductions in WM and smaller total cortical surface area could be central anatomical abnormalities in schizophrenia, driving, at least partially, the reduced regional GM volumes often observed in this illness.  相似文献   

4.

Background

Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.

Methods

Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.

Results

There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.

Conclusions

Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.  相似文献   

5.

Background

A recent modeling study by the authors predicted that contextual information is poorly integrated into episodic representations in schizophrenia, and that this is a main cause of the retrieval deficits seen in schizophrenia.

Methodology/Principal Findings

We have tested this prediction in patients with first-episode schizophrenia and matched controls. The benefit from contextual cues in retrieval was strongly reduced in patients. On the other hand, retrieval based on item cues was spared.

Conclusions/Significance

These results suggest that reduced integration of context information into episodic representations is a core deficit in schizophrenia and one of the main causes of episodic memory impairment.  相似文献   

6.

Background

Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest.

Methods

Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data.

Results

Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD.

Conclusions

Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.  相似文献   

7.

Background

No reliable biomarkers are identified in KLS. However, few functional neuroimaging studies suggested hypoactivity in thalamic and hypothalamic regions during symptomatic episodes. Here, we investigated relative changes in regional brain metabolism in Kleine-Levin syndrome (KLS) during symptomatic episodes and asymptomatic periods, as compared to healthy controls.

Methods

Four drug-free male patients with typical KLS and 15 healthy controls were included. 18-F-fluorodeoxy glucose positron emission tomography (PET) was obtained in baseline condition in all participants, and during symptomatic episodes in KLS patients. All participants were asked to remain fully awake during the whole PET procedure.

Results

Between state-comparisons in KLS disclosed higher metabolism in paracentral, precentral, and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus and putamen during symptomatic episodes, and decreased metabolism in occipital and temporal gyri. As compared to healthy control subjects, KLS patients in the asymptomatic phase consistently exhibited significant hypermetabolism in a wide cortical network including frontal and temporal cortices, posterior cingulate and precuneus, with no detected hypometabolism. In symptomatic KLS episodes, hypermetabolism was additionally found in orbital frontal and supplementary motor areas, insula and inferior parietal areas, and right caudate nucleus, and hypometabolism in the middle occipital gyrus and inferior parietal areas.

Conclusion

Our results demonstrated significant hypermetabolism and few hypometabolism in specific but widespread brain regions in drug-free KLS patients at baseline and during symptomatic episodes, highlighting the behavioral state-dependent nature of changes in regional brain activity in KLS.  相似文献   

8.

Introduction

Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia.

Methods

Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J).

Results

Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients.

Conclusions

This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.  相似文献   

9.

Aim

We sought to use a regional homogeneity (ReHo) approach as an index in resting-state functional magnetic resonance imaging (fMRI) to investigate the features of spontaneous brain activity within the default mode network (DMN) in patients suffering from bipolar depression (BD).

Methods

Twenty-six patients with BD and 26 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. We compared the differences in ReHo between the two groups within the DMN and investigated the relationships between sex, age, years of education, disease duration, the Hamilton Rating Scale for Depression (HAMD) total score, and ReHo in regions with significant group differences.

Results

Our results revealed that bipolar depressed patients had increased ReHo in the left medial frontal gyrus and left inferior parietal lobe compared to healthy controls. No correlations were found between regional ReHo values and sex, age, and clinical features within the BD group.

Conclusions

Our findings indicate that abnormal brain activity is mainly distributed within prefrontal-limbic circuits, which are believed to be involved in the pathophysiological mechanisms underlying bipolar depression.  相似文献   

10.
11.
Liu J  Qin W  Nan J  Li J  Yuan K  Zhao L  Zeng F  Sun J  Yu D  Dong M  Liu P  von Deneen KM  Gong Q  Liang F  Tian J 《PloS one》2011,6(11):e27049

Background

Migraine shows gender-specific incidence and has a higher prevalence in females. However, little is known about gender-related differences in dysfunctional brain organization, which may account for gender-specific vulnerability and characteristics of migraine. In this study, we considered gender-related differences in the topological property of resting functional networks.

Methodology/Principal Findings

Data was obtained from 38 migraine patients (18 males and 20 females) and 38 healthy subjects (18 males and 20 females). We used the graph theory analysis, which becomes a powerful tool in investigating complex brain networks on a whole brain scale and could describe functional interactions between brain regions. Using this approach, we compared the brain functional networks between these two groups, and several network properties were investigated, such as small-worldness, network resilience, nodal centrality, and interregional connections. In our findings, these network characters were all disrupted in patients suffering from chronic migraine. More importantly, these functional damages in the migraine-affected brain had a skewed balance between males and females. In female patients, brain functional networks showed worse resilience, more regions exhibited decreased nodal centrality, and more functional connections revealed abnormalities than in male patients.

Conclusions

These results indicated that migraine may have an additional influence on females and lead to more dysfunctional organization in their resting functional networks.  相似文献   

12.

Background

The rs12807809 single-nucleotide polymorphism in NRGN is a genetic risk variant with genome-wide significance for schizophrenia. The frequency of the T allele of rs12807809 is higher in individuals with schizophrenia than in those without the disorder. Reduced immunoreactivity of NRGN, which is expressed exclusively in the brain, has been observed in Brodmann areas (BA) 9 and 32 of the prefrontal cortex in postmortem brains from patients with schizophrenia compared with those in controls.

Methods

Genotype effects of rs12807809 were investigated on gray matter (GM) and white matter (WM) volumes using magnetic resonance imaging (MRI) with a voxel-based morphometry (VBM) technique in a sample of 99 Japanese patients with schizophrenia and 263 healthy controls.

Results

Although significant genotype-diagnosis interaction either on GM or WM volume was not observed, there was a trend of genotype-diagnosis interaction on GM volume in the left anterior cingulate cortex (ACC). Thus, the effects of NRGN genotype on GM volume of patients with schizophrenia and healthy controls were separately investigated. In patients with schizophrenia, carriers of the risk T allele had a smaller GM volume in the left ACC (BA32) than did carriers of the non-risk C allele. Significant genotype effect on other regions of the GM or WM was not observed for either the patients or controls.

Conclusions

Our findings suggest that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small GM volume in the ACC in the left hemisphere in patients with schizophrenia.  相似文献   

13.

Background:

Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.

Methodology and Principal Findings:

To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer''s disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.

Conclusions:

In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.  相似文献   

14.

Background

Effective and accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) is currently of significant interest. ADHD has been associated with multiple cortical features from structural MRI data. However, most existing learning algorithms for ADHD identification contain obvious defects, such as time-consuming training, parameters selection, etc. The aims of this study were as follows: (1) Propose an ADHD classification model using the extreme learning machine (ELM) algorithm for automatic, efficient and objective clinical ADHD diagnosis. (2) Assess the computational efficiency and the effect of sample size on both ELM and support vector machine (SVM) methods and analyze which brain segments are involved in ADHD.

Methods

High-resolution three-dimensional MR images were acquired from 55 ADHD subjects and 55 healthy controls. Multiple brain measures (cortical thickness, etc.) were calculated using a fully automated procedure in the FreeSurfer software package. In total, 340 cortical features were automatically extracted from 68 brain segments with 5 basic cortical features. F-score and SFS methods were adopted to select the optimal features for ADHD classification. Both ELM and SVM were evaluated for classification accuracy using leave-one-out cross-validation.

Results

We achieved ADHD prediction accuracies of 90.18% for ELM using eleven combined features, 84.73% for SVM-Linear and 86.55% for SVM-RBF. Our results show that ELM has better computational efficiency and is more robust as sample size changes than is SVM for ADHD classification. The most pronounced differences between ADHD and healthy subjects were observed in the frontal lobe, temporal lobe, occipital lobe and insular.

Conclusion

Our ELM-based algorithm for ADHD diagnosis performs considerably better than the traditional SVM algorithm. This result suggests that ELM may be used for the clinical diagnosis of ADHD and the investigation of different brain diseases.  相似文献   

15.

Background

YWHAE is a possible susceptibility gene for schizophrenia that encodes 14-3-3epsilon, a Disrupted-in-Schizophrenia 1 (DISC1)-interacting molecule, but the effect of variation in its genotype on brain morphology remains largely unknown.

Methods

In this voxel-based morphometric magnetic resonance imaging study, we conducted whole-brain analyses regarding the effects of YWHAE single-nucleotide polymorphisms (SNPs) (rs28365859, rs11655548, and rs9393) and DISC1 SNP (rs821616) on gray matter volume in a Japanese sample of 72 schizophrenia patients and 86 healthy controls. On the basis of a previous animal study, we also examined the effect of rs28365859 genotype specifically on hippocampal volume.

Results

Whole-brain analyses showed no significant genotype effect of these SNPs on gray matter volume in all subjects, but we found significant genotype-by-diagnosis interaction for rs28365859 in the left insula and right putamen. The protective C allele carriers of rs28365859 had a significantly larger left insula than the G homozygotes only for schizophrenia patients, while the controls with G allele homozygosity had a significantly larger right putamen than the C allele carriers. The C allele carriers had a larger right hippocampus than the G allele homozygotes in schizophrenia patients, but not in healthy controls. No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.

Conclusions

These different effects of the YWHAE (rs28365859) genotype on brain morphology in schizophrenia and healthy controls suggest that variation in its genotype might be, at least partly, related to the abnormal neurodevelopment, including in the limbic regions, reported in schizophrenia. Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.  相似文献   

16.

Background

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample.

Materials and Methods

FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders.

Results

Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study.

Conclusion

This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.  相似文献   

17.

Background

Phenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main neurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare phenylalanine, tyrosine, and their ratio (a proxy for PAH function) in a relatively large sample of schizophrenia patients and healthy controls.

Methods

We measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls.

Results

Compared to controls, schizophrenia patients had higher phenylalanine (p<0.0001) and phenylalanine: tyrosine ratio (p<0.0001) but tyrosine did not differ between the two groups (p = 0.596).

Conclusions

Elevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be replicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a target for novel preventative and interventional approaches.  相似文献   

18.

Background

Long duration of untreated psychosis (DUP) is associated with poor treatment outcome. Whether or not DUP is related to brain gray matter volume abnormalities in antipsychotic medication treatment naïve schizophrenia remains unclear at this time.

Methods

Patients with treatment-naïve schizophrenia and healthy controls went through brain scan using high resolution Magnetic Resonance Imaging. DUP was evaluated using the Nottingham Onset Schedule (NOS), and dichotomized as short DUP (≤ 26 weeks) or long DUP (>26 weeks). Voxel-based methods were used for volumetric measure in the brain.

Results

Fifty-seven patients (27 short DUP and 30 long DUP) and 30 healthy controls were included in the analysis. There were significant gray matter volumetric differences among the 3 groups in bilateral parahippocampus gyri, right superior temporal gyrus, left fusiform gyrus, left middle temporal gyrus, and right superior frontal gyrus (p''s<0.01). Compared with healthy controls, the long DUP group had significantly smaller volume in all these regions (p''s <0.05). Compared with the short-DUP group, the long-DUP group had significantly smaller volume in right superior temporal gyrus, left fusiform gyrus, and left middle temporal gyrus (p''s<0.01).

Conclusion

Our findings suggest that DUP is associated with temporal and occipitotemporal gray matter volume decrease in treatment naïve schizophrenia. The brain structural changes in untreated psychosis might contribute to poor treatment response and long-term prognosis in this patient population.  相似文献   

19.

Background

Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown.

Methods

Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC).

Results

Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions.

Conclusions

These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.  相似文献   

20.

Objective

To examine the difference between schizophrenia patients and normal controls on velocity and acceleration of saccade, by using the basic visually guided saccade (VGS) paradigm.

Methods

Eighteen schizophrenia outpatients and fourteen normal controls participated in the VGS task. Multiple indicators, including amplitude, duration, velocity, latency, accuracy rate, acceleration, and deceleration were analyzed. Asymmetric acceleration index (AAI) was introduced to describe the difference between peak acceleration and peak deceleration. The correlation coefficient (RAD) of AAI and duration was computed to examine the difference between schizophrenia patients and normal controls.

Results

No significant difference between patients and normal controls was found on amplitude, duration, latency, and accuracy rate. However, RAD values of schizophrenia patients were significantly lower than the control group.

Conclusion

Compared to normal controls, association of saccade duration and saccade acceleration/deceleration asymmetry during visually guided saccade was lower in schizophrenia patients.  相似文献   

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