Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

The effects of childhood trauma on personality in unaffected first-degree relatives of patients with major depressive disorder.

ABSTRAC: OBJECTIVES: This study aimed to preliminarily and exploratorily examine the associations between childhood trauma (CT), its subtypes, and personality traits among unaffected first-degree relatives (FDR, children, or siblings) of patients with major depressive disorder (MDD). METHODS: The study sample included three subgroups: MDD patients (N = 85), Patients' FDRs (N = 35), and healthy control individuals (HC, N = 89). The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma and the Eysenck Personality Questionnaire was used to assess personality traits. RESULTS: Significant differences were found in a few personality traits (p < 0.05 for extraversion, neuroticism, and psychoticism) among MDD patients, FDR, and HC, and there were no significant differences between HC and FDR. In the FDR group, compared with those without CT, participants with CT scored significantly higher for neuroticism (N) (F = 3.246, p = 0.046). CT was significantly associated with N, psychoticism (P) and Lie (L), and the strongest association was between CT total score and N. Significantly positive correlations were found between N and sexual abuse (SA) (r = 0.344, p = 0.043), emotional neglect (EN) (r = 0.394, p = 0.019), physical neglect (PN) (r = 0.393, p = 0.019), and CTQ total score (r = 0.452, p = 0.006); between P and CTQ total score (r = 0.336, p = 0.049); and significant negative correlations were found between L and EN (r = -0.446, p = 0.007), CTQ total score (r = -0.375, p = 0.027). CONCLUSION: In unaffected FDRs, there were significant associations between childhood trauma and a few personality traits, including neuroticism, psychoticism, and lie, and emotional neglect was significantly associated with neuroticism.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Impact of childhood trauma on sensory gating in patients with first-episode schizophrenia.

BACKGROUND: Childhood trauma (CT) has been found to contribute to the onset of schizophrenia and auditory sensory gating deficit is a leading endophenotype for schizophrenia. However, the association between the CT and sensory gating in first-episode schizophrenia remains elusive. METHODS: Fifty-six patients and 49 age and sex-matched healthy controls were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale (PANSS) for symptoms severity. Sensory gating was tested using the modified paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and the perceived spatial co-location PPI (PSC-PPI or classical PPI). RESULTS: Comparing with healthy controls, the patients had significantly higher score on sexual abuse (t = 2.729, p < 0.05), lower PSS- PPI, % (ISI = 120 ms and ISI = 60 ms) (t = - 3.089, - 4.196, p < 0.05). Univariate analysis revealed the absence of a significant correlation among CT, PPI paradigms and symptoms. However, multiple linear regression analyses demonstrated the CTQ-SF total was negatively associated with PSS PPI (ISI = 120 ms) (p = 0.018). CONCLUSION: The current study illustrates that the impact of CT on sensory gating in patients with first-episode schizophrenia, and thus we conclude that CT may be a risk factor to the occurrence of schizophrenia through its impact on sensory gating.

Deficits of perceived spatial separation induced prepulse inhibition in patients with schizophrenia: relationships to symptoms and neurocognition.

BACKGROUND: Prepulse inhibition (PPI) and attention were impaired, which may cause psychotic symptoms and (or) hinder the cognitive functions in schizophrenia. However, due to the measurement methods of PPI, findings about the relationship between PPI and clinical symptoms, cognitive performances have been equivocal. METHODS: Seventy-five schizophrenia patients (SZ) and 50 healthy controls (HC) were assessed in a modified acoustic PPI paradigm, named perceived spatial separation-induced PPI (PSS-PPI), compared to perceived spatial co-location PPI (PSC-PPI) with inter-stimulus interval (ISI) of 120 ms. Repeatable Battery for the Assessment of Neuropsychological Status and the Stroop Color-Word Test were administered to all subjects. RESULTS: Significant decrease in the modified PPI was found in the patients as compared to the controls, and effect sizes (Cohen'd) for patients vs. HCs % PPI levels achieved a significant level (PSC-PPI d = 0.84, PSS-PPI d = 1.27). A logistic regression model based on PSS-PPI significantly represented the diagnostic grouping (χ2= 29.3; p < 0 .001), with 85.2% area under ROC curve in predicting group membership. In addition, patients exhibited deficits in neurocognition. Among patients of "non-remission", after controlling for gender, age, education, duration, recurrence times, onset age, cigarettes per day and chlorpromazine equivalent dosage, PSS-PPI levels were associated with positive and negative symptoms, PANSS total and thought disorder (P1, P6, P7, N5, N7, G9). In multiple linear regression analyses, male and higher attention scores contributed to better PSC-PPI and PSS-PPI in controls group, while larger amount of smoke and longer word-color interfere time contributed to poor PSS-PPI. In patients' group, higher education and attention scores contributed to better PSS-PPI, while repeated relapse contributed to poor PSS-PPI. CONCLUSIONS: The acoustic perceived spatial separation-induced PPIs may bring to light the psychopathological symptoms, especially for thought disorder, and the mechanism(s) of the novel PPI paradigm was associated with attention function.

Effect of childhood trauma on cognitive functions in a sample of Chinese patients with schizophrenia.

In this study, we aimed to determine the influence of various types of childhood trauma (CT) on cognitive functions in Chinese patients presented with schizophrenia. One hundred sixty-two patients were assessed with the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We investigated the correlations between various types of CT, demographic characteristics, and cognitive functions. Significant negative correlations were observed in physical abuse (PA) and sexual abuse (SA) with the language score (r=-0.190, -0.216, respectively, p<0.05). Similarly, physical neglect (PN) and the total score of CTQ were negatively correlated with the attention score (r=-0.17, -0.206, p<0.05, respectively) as well as the total RBANS score (r=-0.199, -0.223, respectively P<0.05). PN was also negatively correlated with delayed memory (r=-0.167, p<0.05). Regressions analysis indicated significant negative correlations between PN and attention, as well as the cognitive total score (p<0.001). Furthermore, demographic variables (years of education, family income) and clinical characteristics (type of anti-psychotics, duration of illness and times of recurrence) were correlated with cognitive functions. The current study showed that different types of CT could impact specific cognitive functions in Chinese schizophrenia patients. Therefore, we recommend that trauma-focused mental interventions for schizophrenia patients should be developed and routinely offered to patients.

Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia: A Prospective, Multicenter Study.

The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms-Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.

BACKGROUND: Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined. AIM: To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism. METHODS: In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale. RESULTS: COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, ß = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, ß = -0.250, 95%CI: -0.495 to -0.004, P = 0.046). CONCLUSION: This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Detection of Schizophrenia Cases From Healthy Controls With Combination of Neurocognitive and Electrophysiological Features.

Background: The search for a method that utilizes biomarkers to identify patients with schizophrenia from healthy individuals has occupied researchers for decades. However, no single indicator can be employed to achieve the good in clinical practice. We aim to develop a comprehensive machine learning pipeline based on neurocognitive and electrophysiological combined features for distinguishing schizophrenia patients from healthy people. Methods: In the present study, 69 patients with schizophrenia and 50 healthy controls participated. Neurocognitive (contains seven specific domains of cognition) and electrophysiological [prepulse inhibition, electroencephalography (EEG) power spectrum, detrended fluctuation analysis, and fractal dimension (FD)] features were collected, all these features were taken together to generate the identification models of schizophrenia by applying logistics, random forest, and extreme gradient boosting algorithm. The classification capabilities of these models were also evaluated. Results: Both the neurocognitive and electrophysiological feature sets showed a good classification effect with the highest accuracy greater than 85% and AUC greater than 90%. Specifically, the performances of the combined neurocognitive and electrophysiological feature sets achieved the highest accuracy of 93.28% and AUC of 97.91%. The extreme gradient boosting algorithm as a whole presented more stably and precisely in classification efficiency. Conclusion: The highest classification accuracy of 93.28% by combination of neurocognitive and electrophysiological features shows that both measurements are appropriate indicators to be used in discriminating schizophrenia patients and healthy individuals. Also, among three algorithms, extreme gradient boosting had better classified performances than logistics and random forest algorithms.

Altered frequency-specific/universal amplitude characteristics of spontaneous brain oscillations in patients with bipolar disorder.

The human brain is a dynamic system with intrinsic oscillations in spontaneous neural activity. Whether the dynamic characteristics of these spontaneous oscillations are differentially altered across different frequency bands in patients with bipolar disorder (BD) remains unclear. This study recruited 65 patients with BD and 85 healthy controls (HCs). The entire frequency range of resting-state fMRI data was decomposed into four frequency intervals. Two-way repeated-measures ANCOVA was employed to detect frequency-specific/universal alterations in the dynamic oscillation amplitude in BD. The patients were then divided into two subgroups according to their mood states to explore whether these alterations were independent of their mood states. Finally, other window sizes, step sizes, and window types were tested to replicate all analyses. Frequency-specific abnormality of the dynamic oscillation amplitude was detected within the posterior medial parietal cortex (centered at the precuneus extending to the posterior cingulate cortex). This specific profile indicates decreased amplitudes in the lower frequency bands (slow-5/4) and no amplitude changes in the higher frequency bands (slow-3/2) compared with HCs. Frequency-universal abnormalities of the dynamic oscillation amplitude were also detectable, indicating increased amplitudes in the thalamus and left cerebellum anterior lobe but decreased amplitudes in the medial superior frontal gyrus. These alterations were independent of the patients' mood states and replicable across multiple analytic and parametric settings. In short, frequency-specific/universal amplitude characteristics of spontaneous oscillations were observed in patients with BD. These abnormal characteristics have important implications for specific functional changes in BD from multiple frequency and dynamic perspectives.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Predictors of relapse in Chinese schizophrenia patients: a prospective, multi-center study.

OBJECTIVE: Relapse prevention is the main goal of maintenance treatment in schizophrenia. This study aimed to determine the rate and the socio-demographic and clinical predictors of relapse in Chinese schizophrenia patients following treatment of the acute phase of the illness. METHODS: In a multi-center, randomized, controlled, longitudinal study, 404 patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to either the maintenance (i.e., initial optimal therapeutic doses continued throughout the study) or the dose-reduction group (i.e., initial optimal therapeutic doses continued for 4 or 26 weeks followed by a 50% dose reduction that was maintained until the end of the study). Participants were interviewed at entry using standardized assessment instruments, and followed up for 12-26 months. RESULTS: In univariate analyses, relapse was significantly associated with the membership of the dose-reduction group, poor medication adherence, and having a diagnosis of the paranoid type of schizophrenia. In Cox proportional-hazards regression analysis the membership of the dose-reduction group, poorer medication adherence, more severe drug-induced side effects and prominent paranoid symptoms independently predicted a higher risk of relapse. CONCLUSION: The study confirmed the importance of maintenance medication in preventing relapse in Chinese schizophrenia patients underscoring the risk of relapse associated with lack of treatment adherence, severe side effects and the patients' paranoid attitude. Socio-demographic characteristics were not associated with relapse in Chinese schizophrenia patients. Potential residual confounding caused by unmeasured variables should be fully considered in future studies.

The Neglect of Left-Behind Children in China: A Meta-Analysis.

OBJECTIVE: To evaluate the neglect of left-behind children (LBC) in China. METHOD: Participants: Children separated from one or both parents for at least 6 months. Intervention: Trauma of separation. Comparison: Non-left-behind children (NLBC). Outcomes: Neglect rates and severity. Only case-control studies were included. RESULTS: Thirteen studies were included; there were 18,688 LBC in a large sample (N = 42,003) of children aged 0-18 years in China. The overall neglect rate was significantly higher in LBC compared to NLBC (odds ratio [OR] = 1.58, 95% confidence interval [CI] = [1.50, 1.67], p < .01) based on the Chinese Rural Child Neglected Evaluation Model (CRCNEM) and the Parents-Child Conflict Tactics Scales (OR = 1.44, 95% CI [1.35, 1.54], p < .01). The overall neglect severity in LBC was also significantly higher than NLBC (SMD = 0.31, 95% CI [0.28, 0.33], p < .01). The same trends were observed in sex subgroups. With regard to subtypes, LBC were significantly more likely to have emotional neglect (OR = 2.29, 95% CI [1.88, 2.78], p < .01), medical neglect (OR = 1.79, 95% CI [1.62, 1.98], p < .01), physical neglect (OR = 1.75, 95% CI [1.60, 1.91], p < .01), security neglect (OR = 1.52, 95% CI [1.32, 1.75], p < .01), educational neglect (OR = 1.50, 95% CI [1.31, 1.72], p < .01), and social neglect (OR = 1.33, 95% CI [1.18, 1.51], p < .01). Furthermore, LBC had significantly higher severity in medical neglect (SMD = 0.31, 95% CI [0.27, 0.35], p < .01), emotional neglect (SMD = 0.28, 95% CI [0.24, 0.32], p < .01), physical neglect (SMD = 0.24, 95% CI [0.18, 0.29], p < .01), security neglect (SMD = 0.26, 95% CI [0.23, 0.29], p < .01), educational neglect (SMD = 0.25, 95% CI [0.20, 0.31], p < .01), and social neglect (SMD = 0.25, 95% CI [0.10, 0.40], p < .01). CONCLUSION: The neglect rates and severity in LBC in China were both significantly higher than those in NLBC. There was a strong association between neglect and LBC. Public policy changes are urgently needed to improve the dire situation and the well-being of the LBC.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Sex differences in patients with schizophrenia: A prospective, multi-center study.

This study aimed to determine sex differences in socio-demographic and clinical characteristics of Chinese schizophrenia patients. In a multi-center, randomized, controlled, longitudinal study, 404 clinically stable patients with schizophrenia were randomly assigned to a maintenance group (optimal therapeutic doses continued throughout the study), a 26-week group (optimal therapeutic doses continued for 26 weeks, followed by a 50% dose reduction maintained until the end of the study), or a 4-week group (optimal therapeutic doses continued for 4 weeks, followed by a 50% dose reduction maintained until the end of the study). Participants were interviewed regularly using standardized assessment instruments, and followed up for 12-26 months. In the univariate analyses, the following factors were significantly associated with the male sex: not married, smoking, younger age, earlier age at onset, higher body mass index (BMI) at baseline, and more severe negative and hostility-excitement symptoms at baseline. The following factors were independently associated with the male sex in the multivariate analyses: not being married, smoking, a higher BMI at baseline, less deterioration in disorganized thoughts (4-week group) and positive symptoms (26-week group) and less increase in BMI in all three treatment groups over the study period. The majority of the sex differences in schizophrenia patients in this study are in accordance with results of previous studies worldwide suggesting that sex differences seen in schizophrenia are not dependent on cultural differences between geographically separate patients.

Cigarette smoking in patients with schizophrenia in China: prospective, multicentre study.

OBJECTIVE: The aim of the present study was to explore the rate of cigarette smoking and its sociodemographic and clinical characteristics in Chinese schizophrenia patients. METHODS: In a multicentre, randomized, controlled, longitudinal study, 374 clinically stable patients with schizophrenia were interviewed at entry using standardized assessment instruments, and followed up for 1-2 years. RESULTS: The rate of cigarette smoking was 13.9% in the whole sample, and 26.2% in men and 3.5% in women. On univariate analysis, male sex, unemployment, alcohol consumption, older age, older age at onset, longer duration of illness, more frequent admissions, more severe hostility-excitement at entry and less deterioration in hostility-excitement over the study period were significantly associated with cigarette smoking. On multivariate analysis, male sex, unemployment, alcohol consumption, more frequent admissions, less severe positive and negative symptoms at entry, smaller decline in negative symptoms and more deterioration in disorganized thoughts over the study period were independently associated with cigarette smoking. CONCLUSION: The rate of cigarette smoking in Chinese schizophrenia patients is considerably lower than most figures reported in the Western literature.