Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

Effects of dietary restriction on cognitive function: a systematic review and meta-analysis.

BACKGROUND: Potential positive link between cognitive function and dietary restriction has been widely concerned. The present study describes a systematic review and preliminary meta-analysis to assess the efficacy of dietary restriction on cognitive function. We classified dietary restrictions as Calories Restriction (CR) and Intermittent Fasting (IF). METHOD: This systematic review and meta-analysis conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA) Checklist, Databases including PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials (RCTs) assessing the cognition effectiveness of dietary restriction from database inception to Sep 2021. RESULT: Eleven RCTs met the inclusion criteria in the systematic review and meta-analysis. The overall effect of dietary restriction on cognitive function is SMD = 0.22 (95% CI: 0.09-0.34, p < 0.01). The effect on global function SMD = 0.35 (95% CI: 0.04-0.65, p < 0.05) and memory SMD = 0.18 (95% CI: 0.00-0.35, p = 0.05) is significant. MCI showed the best effectiveness SMD = 0.36 (95% CI: 0.05-0.68, p < 0.05), followed by the normal weight population SMD = 0.28 (95% CI: 0.03-0.52, p < 0.05) and overweight population SMD = 0.20 (95% CI: 0.06-0.34, p < 0.01). No statistically significant difference showed between IF and CR (p > 0.05). CONCLUSION: Our study demonstrated that dietary restriction has varying degrees of positive effect on cognitive function in overweight/normal-weight people and MCI. However, it should be cautious when generalizing to other populations. Additional high-quality, large-scale, cohort and intervention studies are needed to further assess the effectiveness of dietary restriction on cognition.

Liver Protection of a Low-Polarity Fraction from Ficus pandurata Hance, Prepared by Supercritical CO2 Fluid Extraction, on CCl4-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Ferroptosis Mediated by Strengthened Antioxidation.

Ficus pandurata Hance (FPH) is a Chinese herbal medicine widely used for health care. This study was designed to investigate the alleviation efficacy of the low-polarity ingredients of FPH (FPHLP), prepared by supercritical CO2 fluid extraction technology, against CCl4-induced acute liver injury (ALI) in mice and uncover its underlying mechanism. The results showed that FPHLP had a good antioxidative effect determined by the DPPH free radical scavenging activity test and T-AOC assay. The in vivo study showed that FPHLP dose-dependently protected against liver damage via detection of ALT, AST, and LDH levels and changes in liver histopathology. The antioxidative stress properties of FPHLP suppressed ALI by increasing levels of GSH, Nrf2, HO-1, and Trx-1 and reducing levels of ROS and MDA and the expression of Keap1. FPHLP significantly reduced the level of Fe2+ and expression of TfR1, xCT/SLC7A11, and Bcl2, while increasing the expression of GPX4, FTH1, cleaved PARP, Bax, and cleaved caspase 3. The results demonstrated that FPHLP protected mouse liver from injury induced by CCl4 via suppression of apoptosis and ferroptosis. This study suggests that FPHLP can be used for liver damage protection in humans, which strongly supports its traditional use as a herbal medicine.

The Chinese version of informant AD8 for mild cognitive impairment and dementia screening in community-dwelling older adults.

BACKGROUND: Conducting routine mild cognitive impairment (MCI) and dementia screening for older adults in the community is important, which not only can improve our understanding of these diseases but also can increase early detection and treatment. METHODS: To analyze the reliability and validity of the informant AD8 and explore the cut-off values for screening MCI and dementia in the community-dwelling older adults, this study adopted a multi-stage cluster sampling method to recruit 327 participants aged 60 and over in communities. The informant AD8 and Clinical Dementia Rating (CDR) scales were used to evaluate cognitive function of the subjects, and the receiver operating characteristic curves (ROC) was conducted to test the screening efficacy. RESULTS: Among the 327 participants, 33.0% of them met the criteria of MCI, and 3.4% of them met the criteria of dementia. The area under the receiver operating characteristic curve (AUC) of the informant AD8 for screening dementia was 0.974, with a screening cut-off of three, sensitivity of 90.9% and specificity of 89.0%. But it has a poor discriminability in MCI screening [AUC = 0.645, 95% confidence interval (CI): 0.578-0.711]. CONCLUSIONS: This study suggests that the informant AD8 is an ideal and useful tool for dementia screening in community-dwelling older adults. However, it is less capable to distinguish older adults with MCI from those with normal cognitive function.

Impact of body mass index (BMI) on the success rate of fresh embryo transfer in women undergoing first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.

OBJECTIVE: To investigate the impact of body mass index (BMI) on the success rate and prenatal outcomes of fresh embryo transfer in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. METHODS: It is a post-hoc analysis of a prospective observational cohort study. 2569 Chinese women were grouped in quintiles of BMI and according to the official Chinese classification of body weight. IVF/ICSI and pregnancy outcomes were compared between groups. RESULTS: BMI was not associated with IVF/ICSI pregnancy outcomes including hCG positive rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, ongoing pregnancy rate, early miscarriage rate, and live birth rate. However, it was negatively related to some pregnancy complications such as gestational diabetes mellitus (GDM) and hypertension. Additionally, the proportion of Cesarean-section was increased with BMI. As for prenatal outcomes, the current results showed no statistical difference in the number of male and female newborn, the proportion of low live birth weight (<2500 g), macrosomia (≥4000 g) (both in all live birth and full-term live birth), and premature delivery (<37 weeks). CONCLUSIONS: The current study showed that BMI was not associated with embryo transfer outcomes after fresh embryo transfer in women undergoing their first IVF/ICSI treatment, whereas BMI was associated with GDM and gestational hypertension.

Prevalence and relative factors of health anxiety of elders in community healthcare centers.

OBJECTIVE: The study's aims were (i) to identify the prevalence of health anxiety (HA) among the elderly in urban community healthcare centers and (ii) to determine whether HA is related to social, physical, or psychological factors. DESIGN: It is a population-based observational study. SETTING: Data were collected from urban community healthcare centers in Chengdu, China, from October 2016 to March 2017. PARTICIPANTS: A total of 893 participants aged ≥ 60 years. MEASUREMENTS: The Short HA Inventory was used for HA assessment. Mental health status was assessed using the Geriatric Depression Inventory and Mini-Mental State Examination. Other information was collected through face-to-face interviews. Data analysis was performed using SPSS 19.0. RESULTS: The point prevalence rate of HA was 9.53% (95%CI = 6.99%-12.07%). The number of chronic diseases was a positive factor associated with HA in a regression analysis. As compared with participants without chronic diseases, people with one (OR = 1.796; 95%CI = 0.546-5.909), two (OR = 2.922; 95%CI = 0.897-9.511), and three chronic diseases (OR = 6.448; 95%CI = 2.147-19.363) had higher odds of suffering from HA. CONCLUSIONS: The prevalence of HA was high in the elderly population. Certain physical conditions, such as having chronic diseases, were significant impact factors. More attention should be paid to the situation of HA in this population.

Super-enhancer-driven Sorting Nexin 5 expression promotes dopaminergic neuronal ferroptosis in Parkinson's disease models.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide. Recent studies revealed that the ferroptosis pathway is involved in the death process of dopaminergic neurons in PD. The aberrant endosomal sorting pathway, which results in aberrant iron level in eukaryotic cells, may serve a role in the ferroptosis pathway in PD condition. However, its specific molecular mechanisms remained unclear. In the present study, we performed chromatin immunoprecipitation (ChIP) assay, the rank ordering of super-enhancers (ROSE) algorithm, and RNA interference (RNAi) to explore the regulatory mechanism of PD-specific super-enhancer (SE) in the endosomal sorting pathway and ferroptosis pathway of 6-OHDA-lesioned rats and cells. The ChIP assay and ROSE algorithm results showed that there are specific SEs expression in 6-OHDA-lesioned SNc of PD rats, and the most significant expression gene is Sorting Nexin 5 (SNX5). SNX5 silencing by RNAi experiments significantly decreased the level of ferroptosis in 6-OHDA-lesioned PC12 cells, suggesting the correlation between the SNX5, ferroptosis, and PD. In conclusion, this study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in PD models. This study further improved the understanding of the mechanism of ferroptosis during PD injury and provided potential therapeutic targets and clinical diagnostic markers in PD condition.

Data-driven clustering differentiates subtypes of major depressive disorder with distinct brain connectivity and symptom features.

BACKGROUND: Major depressive disorder (MDD) is a clinically and biologically heterogeneous syndrome. Identifying discrete subtypes of illness with distinguishing neurobiological substrates and clinical features is a promising strategy for guiding personalised therapeutics. AIMS: This study aimed to identify depression subtypes with correlated patterns of functional network connectivity and clinical symptoms by clustering patients according to a weighted linear combination of both features in a relatively large, medication-naïve depression sample. METHOD: We recruited 115 medication-naïve adults with MDD and 129 matched healthy controls, and evaluated all participants with magnetic resonance imaging. We used regularised canonical correlation analysis to identify component mapping relationships between functional network connectivity and symptom profiles, and K-means clustering was used to define distinct subtypes of patients. RESULTS: Two subtypes of MDD were identified: insomnia-dominated subtype 1 and anhedonia-dominated subtype 2. Subtype 1 was characterised by abnormal hyperconnectivity within the ventral attention network and sleep maintenance insomnia. Subtype 2 was characterised by abnormal hypoconnectivity in the subcortical and dorsal attention networks, and prominent anhedonia symptoms. CONCLUSIONS: Our study identified two distinct subtypes of patients with specific neurobiological and clinical symptom profiles. These findings advance understanding of the biological and clinical heterogeneity of MDD, offering a pathway for defining categorical subtypes of illness via consideration of both biological and clinical features.

Poverty transitions in severe mental illness: longitudinal analysis of social drift in China, 1994-2015.

BACKGROUND: Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China. METHODS: Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions. RESULTS: The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty. CONCLUSIONS: This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.

Characteristics of Intrinsic Brain Functional Connectivity Alterations in Major Depressive Disorder Patients With Suicide Behavior.

BACKGROUND: The intrinsic brain functional connectivity of suicide attempts in major depressive disorder (MDD) remains incompletely understood. PURPOSE: To investigate graph-theoretical based functional connectivity strength (FCS) alterations in MDD patients with suicidal behavior. STUDY TYPE: Prospective. SUBJECTS: Fifty medication-free MDD patients, with (suicide attempters, SA, N = 15) and without (non-attempters, nSA, N = 35) a history of a suicide attempt, and 37 healthy controls (HC). FIELD STRENGTH/SEQUENCE: Resting-state functional magnetic resonance imaging (fMRI) using a gradient-echo imaging sequence was acquired at 3.0 T. ASSESSMENT: For each individual, voxel-wise whole-brain functional network was constructed and graph-theoretical based FCS map was calculated. For each individual in two patient groups, the seed-based functional connectivity map was constructed. STATISTICAL TESTS: Non-parameter permutation tests, analysis of covariance, two-sample t-test, Chi-square test, and Pearson correlation analysis. A P value <0.05 was considered statistically significant. RESULTS: Relative to the HC group, two MDD patient groups showed significantly lower FCS in the left hippocampus, while nSA patients showed additionally lower FCS in more widespread regions (P < 0.05). Importantly, comparing to nSA patients, SA patients had significantly higher FCS in the right orbitofrontal cortex (OFC) and bilateral dorsomedial prefrontal cortex (dmPFC) (P < 0.05). Further seed-based functional connectivity analysis revealed that the right OFC exhibited significantly higher connectivity to right middle frontal gyrus and lower connectivity to the left anterior cingulate cortex and left calcarine sulcus, and the bilateral dmPFC had significantly higher connectivity to the left middle frontal gyrus and right inferior temporal gyrus in the SA patients than in the nSA patients (P < 0.05). DATA CONCLUSION: This study identified disconnections of the OFC and dmPFC which were putatively related to a higher risk of suicidal behavior in MDD patients, thus extended the understanding of suicidal behavior at a brain circuit level. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Mental Health Multimorbidity among Caregivers of Older Adults During the COVID-19 Epidemic.

OBJECTIVE: To investigate mental health status and associated factors among caregivers of older adults during the COVID-19 epidemic in China. METHODS: From March 1 to 31, 2020, 916 caregivers of older adults participated in an online cross-sectional survey on the prevalence of anxiety, depression, and sleep problems. The seven-item Generalized Anxiety Disorder Scale (GAD-7) was administered to measure anxiety symptoms, the two-item Patient Health Questionnaire (PHQ-2) was used to assess depressive symptoms, and a self-developed questionnaire was used to assess sleep quality and duration. Six questions about COVID-19-related experiences were used to assess community-level infection contact and the level of exposure to media information. The prevalence rates of anxiety, depression and sleep problems were computed. The Wald χ2 were applied to compare the differences between subgroups. Multiple logistic regression analyses were performed to investigate factors associated with anxiety, depression, sleep problems, and multimorbidity. RESULTS: The prevalence rates of anxiety, depression, and sleep problems were 46.8%, 29.8%, and 10.8%, respectively. Approximately 263 participants (28.7%) presented with two or more mental health problems. Being female (OR, 2.254; 95% CI, 1.510-3.363), having community-level COVID-19 contact (OR, 1.856; 95% CI, 1.189-2.898), and having a mental disorder (OR, 3.610; 95% CI, 1.644-7.930) were associated with increased risk of multimorbidity among caregivers. Caregivers who preferred positive information (OR, 0.652; 95% CI, 0.472-0.899) had reduced risk of multimorbidity. CONCLUSION: Anxiety and depression were common among caregivers of older adults during the COVID-19 epidemic. Being female and having community-level COVID-19 contact were independent risk factors for experiencing multiple mental health problems. Preexisting mental disorders increased the risk of multimorbidity among caregivers, while enhanced access to positive media information decreased the risk of multimorbidity.

Establishing cut-off scores for the self-rating AD8 based on education level.

This study aimed to explore the threshold of self-rating AD8 in mild cognitive impairment (MCI) and dementia screening among community-dwelling older adults with and without education. 523 participants in Chengdu, China, were recruited: 346 with normal cognitive function, 160 with MCI and 17 with dementia. At the cut-off score of 2, the area under the receiver operator characteristic curves (AUC) of self-rating AD8 for MCI and dementia screening was 0.607 and 0.931 regardless of educational level, respectively. Grouping by educational level, the cut-off in MCI screening was 1 for literate (AUC=0.662) and 2 for illiterate individuals (AUC=0.588). For dementia screening, the cut-off was 2 for illiterate (AUC=0.912) and 4 for literate individuals (AUC=0.963). We concluded that the self-rating AD8 was ideal for dementia screening in community-dwelling older adults, with a cut-off score of 2 for illiterate and 4 for literate people, while its effectiveness for MCI screening required further evaluation.

Heterogeneity in the dynamic change of cognitive function among older Chinese people: A growth mixture model.

OBJECTIVES: Our aim is to distinguish different trajectories of cognitive change in Chinese geriatric population and identify risk factors for cognitive decline in each subpopulation. METHODS: We obtained data from five waves (2002, 2005, 2008, 2011, 2014) of the Chinese Longitudinal Health Longevity Survey, using the Chinese Mini-Mental State Examination (C-MMSE) as a proxy for cognitive function. We applied growth mixture modeling (GMM) to identify heterogeneous subpopulations and potential risk factors. RESULTS: Our sample included 3859 older adults, 1387 (48.7%) male and 1974 (51.2%) female with age range of 62 to 108 (average of 74.5) at initial survey. Using GMM and best fit statistics, we identified two distinct subgroups in respect to their longitudinal cognitive function: (a) cognitively stable (87.8%) group with 0.49 C-MMSE points decline per 3 years, and (b) cognitively declining (12.2%) group with 6.03 C-MMSE points decline per 3 years. Of note, cognitive activities were protective, and hearing and visual impairments were risk factors in both groups. Diabetes, hypertension, stroke and cardiovascular disease were associated with cognitive decline in the cognitively declining group. Physical activities, and intake of fresh vegetables, fruits, and fish products were protective in the cognitively stable group. CONCLUSIONS: Using GMM, we identified heterogeneity in trajectories of cognitive change in older Chinese people. Moreover, we found risk factors specific to each subgroup, which should be considered in future studies.

[Study on molecular mechanism of Solanum nigrum in treatment of hepatocarcinoma based on network pharmacology and molecular docking].

This study aimed to explore the main active ingredients and potential targets of Solanum nigrum(SN), so as to reveal the potential molecular mechanism of SN in the treatment of hepatocellular carcinoma(HCC) based on network pharmacology and molecular docking. First,the main active ingredients and predictive targets of SN were collected in the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Then,the targets relating to HCC were collected through retrieval of integrated bio-pharmacological network database for traditional Korean medicine(PharmDB-K), oncogenomic database of hepatocellular carcinoma(OncoDB.hcc). The common targets of disease-drug component were selected through intersection between predictive targets and disease targets. Next, based on the String platform, protein-protein interaction network(PPI) model of the potential anti-HCC targets was constructed using the software Cytoscape 3.7.1. ClueGO and CluePedia APP in Cytoscape were used to analyze the gene function of SN in the treatment of HCC, and construct the main active ingredients-potential targets-signal pathways topology network of SN. Finally,DISCOVERY STUDIO software was applied in verifying the molecular docking between the key active ingredient and potential protein target. The results showed that there were 4 main active ingredients of SN, involving 22 potential targets relating to HCC and 7 signal pathways relating to potential anti-HCC targets of SN. Network analysis showed that SN may play a therapeutic role in HCC by acting on key targets, such as EGFR, TP53, MYC, CCND1 and CTNNB1. Molecular docking results showed that quercetin and EGFR could bind stably and interact through amino acid residues LEU718, LYS745 and GLN791. This study revealed the potential active ingredients and the possible molecular mechanism of SN for treatment of HCC, providing scientific basis for follow-up exploration of the molecular mechanism of SN against HCC.

Large-scale white matter network reorganization in posttraumatic stress disorder.

Recently, graph theoretical approaches applied to neuroimaging data have advanced understanding of the human brain connectome and its abnormalities in psychiatric disorders. However, little is known about the topological organization of brain white matter networks in posttraumatic stress disorder (PTSD). Seventy-six patients with PTSD and 76 age, gender, and years of education-matched trauma-exposed controls were studied after the 2008 Sichuan earthquake using diffusion tensor imaging and graph theoretical approaches. Topological properties of brain networks including global and nodal measurements and modularity were analyzed. At the global level, patients showed lower clustering coefficient (p = .016) and normalized characteristic path length (p = .035) compared with controls. At the nodal level, increased nodal centralities in left middle frontal gyrus, superior and inferior temporal gyrus and right inferior occipital gyrus were observed (p < .05, corrected for false-discovery rate). Modularity analysis revealed that PTSD patients had significantly increased inter-modular connections in the fronto-parietal module, fronto-striato-temporal module, and visual and default mode modules. These findings indicate a PTSD-related shift of white matter network topology toward randomization. This pattern was characterized by an increased global network integration, reflected by increased inter-modular connections with increased nodal centralities involving fronto-temporo-occipital regions. This study suggests that extremely stressful life experiences, when they lead to PTSD, are associated with large-scale brain white matter network topological reconfiguration at global, nodal, and modular levels.

Psychoradiologic abnormalities of white matter in patients with bipolar disorder: diffusion tensor imaging studies using tract-based spatial statistics

Background: An increasing number of psychoradiology studies that use tract-based spatial statistics (TBSS) of diffusion tensor imaging have reported abnormalities of white matter in patients with bipolar disorder; however, robust conclusions have proven elusive, especially considering some important clinical and demographic factors. In the present study, we performed a quantitative meta-analysis of TBSS studies to elucidate the most consistent white-matter abnormalities in patients with bipolar disorder. Methods: We conducted a systematic search up to May 2017 for all TBSS studies comparing fractional anisotropy (FA) between patients with bipolar disorder and healthy controls. We performed anisotropic effect size­signed differential mapping meta-analysis. Results: We identified a total of 22 data sets including 556 patients with bipolar disorder and 623 healthy controls. We found significant FA reductions in the genu and body of the corpus callosum in patients with bipolar disorder relative to healthy controls. No regions of increased FA were reported. In subgroup analyses, the FA reduction in the genu of the corpus callosum retained significance in patients with bipolar disorder type I, and the FA reduction in the body of the corpus callosum retained significance in euthymic patients with bipolar disorder. Meta-regression analysis revealed that the percentage of female patients was negatively correlated with reduced FA in the body of the corpus callosum. Limitations: Data acquisition, patient characteristics and clinical variables in the included studies were heterogeneous. The small number of diffusion tensor imaging studies using TBSS in patients with bipolar disorder type II, as well as the lack of other clinical information, hindered the application of subgroup meta-analyses. Conclusion: Our study consistently identified decreased FA in the genu and body of the corpus callosum, suggesting that interhemispheric communication may be the connectivity most affected in patients with bipolar disorder.

Validation of neuropsychological tests for the China Health and Retirement Longitudinal Study Harmonized Cognitive Assessment Protocol.

OBJECTIVE: To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS. METHODS: We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents' functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents' cognitive status independently. RESULTS: The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status. CONCLUSION: A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.