The Mediation Role of Sleep Disturbances between Vitamin D and Depressive Symptoms: A Cross-Sectional Study.

Depression and sleep disturbances are highly prevalent health problems that have been suggested to be associated with vitamin D deficiency. This study investigated whether sleep disturbances affect the association between vitamin D and depressive symptoms. A total of 425 patients with depression were included in this study. Spearman correlation coefficients were chosen to assess the relation between vitamin D concentrations and depressive symptomatology (according to the PHQ-9 and HAMD-17 scores). The GLM Mediation Model in the Medmod module for data analysis in Jamovi 2.2.5 was used to analyze the mediation models for sleep disturbances. Vitamin D concentrations were significantly correlated with PHQ-9 and HAMD-17 scale scores. In addition, item 3 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of PHQ-9, and item 4 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of HAMD-17. Sleep disturbances (especially difficulty falling asleep) are mediators between vitamin D and depressive symptoms, suggesting that increasing vitamin D levels at the right time to regulate sleep disturbances may improve depression symptoms, yet further research is necessary.

The influence of EEG channels and features significance on automatic detection of epileptic waves in MECT.

Modified Electric Convulsive Therapy (MECT) is an efficacious physical therapy in treating mental disorders. The occurrence of epilepsy is a crucial benchmark for evaluating therapeutic effectiveness. However, the medical field still lacks relevant research on automatically detecting epileptic waves in MECT. Therefore, this article proposes a novel automatic detection method of epileptic waves in MECT. In this article, EEG local features (time, frequency, and time-frequency domains) and global features (Pearson correlation coefficient) are combined for epileptic wave detection with SVM (Support Vector Machine). We researched the system with 15 EEG detection channels. The dataset under investigation contains EEG data from 22 patients who received MECT and presented with epileptic seizures. The results revealed that LA (Logarithm of Activity) feature exhibits the best classification significance. When epileptic waves appear, there is a decrease in the power ratio of delta waves and an increase in the power ratio of theta waves. Additionally, the complexity of EEG decreases while the correlation between EEG channels increases. The Cz, F4, and P3 channels exhibit the highest classification significance among all EEG channels. Furthermore, based on the channel classification significance, the EEG detection channels number can be reduced to 8. Similarly, based on the feature classification significance, the local feature number can be reduced from 9 to 3. These conclusions can improve detection efficiency and reduce the cost for MECT. Moreover, the method we proposed can effectively detect epileptic waves in MECT. This work can provide physicians with a reference for evaluating the effectiveness of MECT.

Effects of Early Adverse Life Events on Depression and Cognitive Performance from the Perspective of the Heart-Brain Axis.

Early adverse life events (EALs) increase susceptibility to depression and impair cognitive performance, but the physiological mechanisms are still unclear. The target of this article is to clarify the impact of adverse childhood experiences on emotional and cognitive performance from the perspective of the heart-brain axis. We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test cognitive function and the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Heart rate variability (HRV) and electroencephalograms (EEG) were acquired at rest. We observed that subjects with depression had experienced more traumatic events during their childhood. Furthermore, they exhibited lower heart rate variability and higher power in the delta, theta, and alpha frequency bands. Moreover, heart rate variability partially mediated the association between childhood trauma exposure and depressive symptoms. Our findings suggested that adverse life events in childhood could influence the development of depression in adulthood, which might be linked to cardiac autonomic dysfunction and altered brain function.

Striatum-related spontaneous coactivation patterns predict treatment response on positive symptoms of drug-naive first-episode schizophrenia with risperidone monotherapy.

Background: Evidence from functional magnetic resonance imaging (fMRI) studies of schizophrenia suggests that interindividual variation in the stationary striatal functional circuit may be correlated with antipsychotic treatment response. However, little is known about the role of the dynamic striatum-related network in predicting patients' clinical improvement. The spontaneous coactivation pattern (CAP) technique has recently been found to be important for elucidating the non-stationary nature of functional brain networks. Methods: Forty-two drug-naive first-episode schizophrenia patients underwent fMRI and T1W imaging before and after 8 weeks of risperidone monotherapy. The striatum was divided into 3 subregions, including the putamen, pallidum, and caudate. Spontaneous CAPs and CAP states were utilized to measure the dynamic characteristics of brain networks. We used DPARSF and Dynamic Brain Connectome software to analyze each subregion-related CAP and CAP state for each group and then compared the between-group differences in the neural network biomarkers. We used Pearson's correlation analysis to determine the associations between the neuroimaging measurements with between-group differences and the improvement in patients' psychopathological symptoms. Results: In the putamen-related CAPs, patients showed significantly increased intensity in the bilateral thalamus, bilateral supplementary motor areas, bilateral medial, and paracingulate gyrus, left paracentral lobule, left medial superior frontal gyrus, and left anterior cingulate gyrus compared with healthy controls. After treatment, thalamic signals in the putamen-related CAP 1 showed a significant increase, while the signals of the medial and paracingulate gyrus in the putamen-related CAP 3 revealed a significant decrease. The increase in thalamic signal intensity in the putamen-related CAP 1 was significantly and positively correlated with the percentage reduction in PANSS_P. Conclusion: This study is the first to combine striatal CAPs and fMRI to explore treatment response-related biomarkers in the early phase of schizophrenia. Our findings suggest that dynamic changes in CAP states in the putamen-thalamus circuit may be potential biomarkers for predicting patients' variation in the short-term treatment response of positive symptoms.

Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics.

Background: Antipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications. Methods: Utilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement. Results: We detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms. Conclusions: This study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a "three-step" roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.

Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis.

Controversial results of the association between maternal body mass index (BMI) and risk of autism spectrum disorder (ASD) in offspring were reported among several studies. This meta-analysis was conducted to estimate the overall association between maternal BMI and risk of ASD in offspring. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched until January 2016. Cohort and case-control studies addressing the association between maternal BMI and risk of ASD in offspring were included. We used random-effect models to estimate the summary relative risks (RRs), we also performed a dose-response meta-analysis to estimate the trend from the correlated log RR estimates across levels of BMI quantitatively. Totally, 6 cohort studies and 1 case-control study involving 8,403 cases and 509,167 participants were included for analysis. The summary RR (95% confidence interval) for ASD in offspring in relation to maternal underweight, overweight, and obesity vs. normal weight during pre-pregnancy or pregnancy, was 1.07 (0.93, 1.23), 1.28 (1.19, 1.36) and 1.36 (1.03, 1.78), respectively. A linear dose-response relationship was found, with a pooled RR of 1.16 (1.01, 1.33) for each 5 kg/m2. increment in maternal BMI. The present study suggests that excessive maternal BMI is associated with increased ASD risk in offspring.

Association between diabetes and risk of suicide death: A meta-analysis of 3 million participants.

BACKGROUND: Results of the relationships between diabetes and the risk of suicide death are inconclusive. This meta-analysis was conducted to assess this association. METHODS: We systematically searched PubMed, EMBASE, Web of Science and the Cochrane Library up to February 29, 2016 for relevant observational studies regarding the association between diabetes and risk of suicide. Random-effects models were used to calculate summary relative risk (RR) and 95% confidence interval (CI). RESULTS: 6 observational studies (8 independent reports) with a total of 3,075,214 participants and 3038 suicide deaths events were included in the meta-analysis. Overall, diabetes was not associated with risk of suicide deaths, with significant heterogeneity among studies observed (Summary RR=1.61, 95% CI: 0.91-2.83, Pheterogeneity<0.001, I2=97.2%). No publication bias was detected across studies, and both the subgroup analysis and sensitivity analysis suggested that the general result was robust. CONCLUSION: Our meta-analysis based on more than 3 million participants indicates that diabetes is not associated with increased risk of suicide death. Further well-designed prospective cohort studies are needed to confirm the findings of this meta-analysis.

Normalization of Intrinsic Neural Circuits Governing Tourette's Syndrome Using Cranial Electrotherapy Stimulation.

GOAL: The aim of this study was to investigate the normalization of the intrinsic functional activity and connectivity of TS adolescents before and after the cranial electrotherapy stimulation (CES) with alpha stim device. METHODS: We performed resting-state functional magnetic resonance imaging on eight adolescents before and after CES with mean age of about nine-years old who had Tourette's syndrome with moderate to severe tics symptom. Independent component analysis (ICA) with hierarchical partner matching method was used to examine the functional connectivity between regions within cortico-striato-thalamo-cortical (CSTC) circuit. Granger causality was used to investigate effective connectivity among these regions detected by ICA. We then performed pattern classification on independent components with significant group differences that served as endophenotype markers to distinguish the adolescents between TS and the normalized ones after CES. RESULTS: Results showed that TS adolescents after CES treatment had stronger functional activity and connectivity in anterior cingulate cortex (ACC), caudate and posterior cingulate cortex while had weaker activity in supplementary motor area within the motor pathway compared with TS before CES. CONCLUSION: The results suggest that the functional activity and connectivity in motor pathway was suppressed while activities in the control portions within CSTC loop including ACC and caudate were increased in TS adolescents after CES compared with adolescents before CES. SIGNIFICANCE: The normalization of the balance between motor and control portions of the CSTC circuit may result in the recovery of TS adolescents.

Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.

OBJECTIVES: Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. METHODS: iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.

Abnormal frontal cortex white matter connections in bipolar disorder: a DTI tractography study.

OBJECTIVE: In bipolar disorder, white matter abnormalities have been reported with region-of-interest and voxel-based methods; however, deficits in specific white matter tracts cannot be localized by these methods. Therefore, in this study, we aimed to investigate the white matter tracts that mediate connectivity of the frontal cortex using diffusion tensor imaging (DTI) tractography. METHODS: Eighteen patients with bipolar disorder and sixteen age- and gender-matched healthy subjects underwent DTI examinations. Frontal cortex white matter tracts, including the anterior thalamic radiation (ATR), uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), cingulum, and inferior fronto-occipital fasciculus (IFO) were reconstructed by DTI tractography, and we calculated the mean fractional anisotropy (FA) for each fiber tract. The values were compared between groups by repeated measures analysis of variance with age and gender as covariates, which allowed us to investigate significant differences between the tracts. RESULTS: When compared with healthy controls, the patients with bipolar disorder showed significantly decreased FA in the ATR and UF, and a trend towards lower FA in the SLF and cingulum. However, there were no FA differences between groups in the IFO. CONCLUSIONS: Our study indicates that bipolar patients show abnormalities within white matter tracts connecting the frontal cortex with the temporal and parietal cortices and the fronto-subcortical circuits. These findings suggest that alterations in the connectivity of white matter tracts in the frontal cortex might contribute to the neuropathology of bipolar disorder.

Comparison of the Addition of Siberian Ginseng (Acanthopanax senticosus) Versus Fluoxetine to Lithium for the Treatment of Bipolar Disorder in Adolescents: A Randomized, Double-Blind Trial.

BACKGROUND: Bipolar disorder (BD) is a common, recurrent, and often life-long major psychiatric condition characterized by manic, depressive, and mixed episodes. Without treatment, there is substantial risk for morbidity and mortality, making BD a considerable public health problem. OBJECTIVE: The purpose of this study was to compare the relative effectiveness and tolerability of Acanthopanax senficosus (A senficosus)-an herb that is derived from eleutherosides and polysaccharides found in the plant's root- versus fluoxetine added to lithium in the treatment of BD in adolescents. METHODS: This was a double-blind, 6-week study. The patients were randomized into 2 treatment groups-A senticosus plus lithium (A senticosus group) and fluoxetine plus lithium (fluoxetine group). The patients underwent a baseline assessment using the 17-Item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) during the screening period. Patients were scheduled for clinical visits at the end of weeks 1, 2, 4, and 6. At the end of the 6-week treatment period, each patient's condition was rated as follows: response (indicating an improvement of ≥50% in the HAMD-17 score from baseline); remission (a HAMD-17 score of ⪯7); and switching to mania (a YMRS score >16, and meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] for a manic episode). At each visit (with the exception of the enrollment visit), the patients were queried as to whether they experienced any health problems since the previous visit, a Treatment Emergent Symptom Scale assessment was completed, and the serum lithium concentration was analyzed. The patients were instructed to report adverse events (AEs) at any time during the study. AEs were also observed by the investigator(s) at clinical visits. RESULTS: Seventy-nine Chinese adolescents were initially enrolled into the study. However, 76 adolescents were assessed for inclusion (45 females, 31 males; mean [SD] age, 15.4 [30.0] years; age range, 12-17 years) in the study. All included patients completed the study. After 6 weeks of treatment, the response rate between the A senticosus and the fluoxetine groups was similar (67.6% vs 71.8%, respectively). The remission rate between both groups was also similar (51.4% vs 48.7%). Analyzed by a general line model, the HAMD-17 scores revealed there was a significant time effect (F = 183.06; P < 0.01), but not a significant group effect (F = 0.99) or group-by-duration of treatment interaction (F = 0.779). Three patients in the fluoxetine group experienced switching to mania compared with no patient in the A senticosus group. AEs reported by patients in the A senticosus group were as follows: nausea, 2 (5.4%); rash, 1 (2.7%); and diarrhea, 1 (2.7%). AEs reported by patients in the fluoxetine group were as follows: nausea, 4 (10.3%); anxiety, 3 (7.7%); insomnia, 3 (7.7%); constipation, 1 (2.6%); and tinnitus, 1 (2.6%). CONCLUSION: Our study found no significant difference in these adolescents with BD treated with lithium plus adjunctive A senticosus or fluoxetine. All treatments were generally well tolerated.