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We present a long-term seasonal tree ring cellulose oxygen isotope (δ18Oc) time series created by analyzing four segments (S1, S2, S3, and S4) per year during the period of 1951–2009 from southeastern Tibetan Plateau. This intraseasonal δ18Oc reveals the onset and mature phase of the summer monsoon precipitation in this region. Analysis indicates that the δ18Oc of S1 has the strongest correlation with precipitation during the regional monsoon onset (29–33 pentads, May 21–June 10, r = −0.69), and the δ18Oc values for S2, S3, and S4 correlate strongly with June, July, and August precipitation, respectively. Combined δ18Oc of S2, S3, and S4 shows the most robust correlation (r = −0.82) with the mature-phase monsoon precipitation (June-July-August, JJA), passing rigorous statistical tests for calibration and verification in dendroclimatology. These results demonstrate the feasibility in using long-term intraseasonal δ18Oc to reconstruct the Asian summer monsoon's intraseasonal variations.
Many studies showed the differences in subjective response to sexual stimuli between heterosexual and homosexual men. However, the underlying neurobiological factors of sexual orientation are largely unknown. We addressed the question what is the major attribution of the expected differences in brain activation, i.e. neural circuits or different cognitive process. Twenty-eight healthy male volunteers, 14 heterosexuals and 14 homosexuals, were scanned by functional Magnetic Resonance Imaging while subjects were viewing different types of stimuli, i.e. heterosexual couple stimuli (HCS), gay couple stimuli (GCS), lesbian couple stimuli (LCS) and neutral stimuli (NS). SPM02 was used for data analysis. Rating of sexual attractiveness was assessed. Subjective sexual arousal was induced by HCS and GCS in heterosexual and homosexual men, respectively. And sexual disgust was induced by GCS and LCS in heterosexual and homosexual men, respectively. As compared to viewing NS, viewing sexual stimuli induced significant different brain activations most of which had characteristic for cognitive process. These observations suggested that different cognitive pattern was major attribution of different subjective response to sexual stimuli between heterosexual and homosexual men.
Genetic variation of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The negative symptom is a severe form of the illness related to prefrontal hypodopaminergia. In the present study, we attempted to perform a quantitative trait test for genetic association between the COMT gene and the negative symptoms in a Chinese population.
A total of 160 unrelated schizophrenic individuals were recruited for genetic analysis and their symptoms were assessed and scored by Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program to see the correlation between scored negative symptoms and some single nucleotide polymorphisms (SNPs) present in the COMT gene.
rs362204 (Del/Ins SNP) showed allelic association with four negative symptoms, including blunted affect (p=0.00008), poor rapport (p=0.00006), passive/apathetic social withdrawal (p=0.0003) and lack of spontaneity and flow of conversation (p=0.001). The rs165656(C)-rs6267(G)-rs4680 (G)-rs362204 (Del) haplotype was strongly associated with both blunted affect (p=0.0245) and poor rapport (p=0.0186).
The present study suggests that COMT may etiologically contribute to the severity of negative symptoms of schizophrenia but its precise mechanism needs further investigating.
The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists. The possible mechanism of the refractory schizophrenia included diagnostic errors, medical conditions and brain dysgensis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucination and persecutory delusion and so on. We reexamined all his possible medical conditions and found the patient had an abnormal enlarged Cavus Septum Pellucidum (CSP) combined with Cavum Vergae (CV) (maximum length>30 mm). Some reports suggested that abnormal CSP(length>6 mm) has an significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may lead to schizophrenia and worse prognosis.
The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.
An increasing number of studies have described the relationship between velo-cardio-facial syndrome (VCFS) and schizophrenia. in a family-based study, we found that rs10314, a single nucleotide polymorphism (SNP) present in the 3’-flanking region of the CLDN5 gene, was associated with schizophrenia among a Chinese population. High false positive rate is a common problem with the association study of human diseases. It is very important to replicate an initial finding with different samples and experimental designs.
A total of 749 patients with schizophrenia and 383 age and sex matched healthy control subjects in Chinese population were recruited. PCR-based RFLP protocol was applied to genotype rs10314 to see its disease association.
The χ2 goodness-of-fit test showed that the genotypic distributions of rs10314 were in Hardy-Weinberg equilibrium in both the patient group (χ2=1.12, P=0.289) and the control group (χ2=0.22, P=0.639). rs10314 was associated with schizophrenia with an odds ratio (OR) of 1.32 in the male subjects (χ2=5.45, P=0.02, 95% CI 1.05-1.67) but not in the female subjects (χ2=0.64, P=0.425, OR=1.14, 95% CI 0.83-1.57). the χ2 test showed a genotypic association only for combined samples (χ2=7.80, df=2, P=0.02). SNP rs10314 is a G to C base change. Frequency of the genotypes containing the C allele was significantly higher in the patient group than in the control group.
The present work shows that the CLDN5 gene polymorphism is more likely to be involved in schizophrenic men than women, suggesting that this gene may contribute to the gender differences in schizophrenia.
Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.
This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.
To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).
Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.
Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.
In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.
The majority of neuroimaging studies reported smaller hippocampal volumes in patients with posttraumatic stress disorder (PTSD). Our previous study found that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields However, the causality of smaller hippocampal volumes and PTSD cannot be determined in these studies because of the cross-sectional nature of them. The purpose of this longitudinal study was to determine if PTSD caused hippocampal subfields volume loss following traffic accidents. Volumes of hippocampal subfields in thirty seven traffic accident survivors were measured using 3T MRI in one week after accident, and twenty five of them completed one year follow-up MRI scan. Fourteen participants met the PTSD diagnosis in one year follow-up while other eleven did not met PTSD diagnosis criteria. PTSD was significantly associated with volumes reduction of CA3/dentate gyrus subfield (β=0.244 p=0.017) while other subfields were spared. It also shown volume loses of Entorhinal Cortex (ERC) of both side in one year follow-up for the whole sample (mean volume reduction: right 19.25mm3, left 22.04 mm3). But no association has been found between PTSD and ERC volume alteration. The findings indicate for the first time in humans that selective volume loss of the CA3/dentate gyrus subfields is the results but not the risk factor of PTSD. It also suggested that ERC may also be a stress sensitive region.
Recent imaging studies have shown that brain morphology and neural activity during sexual arousal differ between homosexual and heterosexual men. Whether the structural and task-related functional differences also exist in the resting state is unknown. The purpose of the study is to characterize the association of homosexual preference with measures of regional homogeneity and functional connectivity in the resting state. Participants were 26 homosexual men and 26 age-matched heterosexual men. The sexual orientation of every participant was evaluated using the Kinsey Scale. We first assessed group differences in regional homogeneity and then, taking the identified differences as seed regions, we compared groups in measures of functional connectivity from those seeds. The behavioral significances of the differences in regional homogeneity and functional connectivity were assessed by examining their associations with scores on the Kinsey Scale. Homosexual participants showed significantly reduced regional homogeneity in the left inferior occipital gyrus, right middle occipital gyrus, right superior occipital gyrus, left cuneus, right precuneus, and increased regional homogeneity in the rectal gyrus, bilateral midbrain, and left temporal lobe. Regional homogeneity correlated positively with Kinsey scores in the left inferior occipital gyrus. The homosexual group also showed reduced functional connectivity in left middle temporal gyrus, left supra-marginal gyrus and right cuneus. In addition, the connection between the left inferior occipital gyrus and right thalamus in the homosexual group was correlated positively with Kinsey scores. This differences in homogeneity and fucntional connectivity may contribute to a better understanding of the neural basis of male sexual orientation.
Increasing evidence indicates that major depressive disorder (MDD) is associated with cognitive as well as mood disturbances.
To evaluate cognitive function and white matter structure, resting-state brain function in first-episode, treatmentnaive patients with MDD.
To explore brain structure and function mechanisms of cognitive impairment in MDD.
46 Han Chinese MDD patients aged 18–45 year and 46 controls were assessed by a series of validated test procedures.Then, 30 patients and 30 controls were obtained by MRI scan.White matter abnormalities evaluated using diffusion tensor imaging (DTI) were analyzed using tract based spatial statistics (TBSS) and resting-state brain function was evaluated using regional homogeneity (ReHo) analysis.
Cognitive impairment in patients with MDD was demonstrated by reduced accuracy in the Wisconsin Card Sorting test (WSCT) and to a lesser extent the Continuous Performance test (CPT) and Trail Making tests (TMT). White matter abnormalities found in the left cerebellum, and resting-state abnormalities present in the left inferior parietal gyrus, left anterior cingulate nucleus and left hippocampal gyrus were associated with impaired performance in the WSCT and CPT tests. We also showed that poor WSCT performance was associated with increased interconnectivity between the left ventral anterior cingulate nucleus and the medial frontal lobe areas.
The present study indicates cognitive disturbances in patients with MDD are associated with white matter and resting-state changes and altered interconnections in specific brain areas.
We describe an analytical method of SH-SY5Y cell membrane chromatography (SH-SY5Y/CMC) for recognition, separation and identification of active components from traditional Chinese medicines (TCMs). SH-SY5Y cells by means of culture with SH-SY5Y cell lines were used for preparation of the stationary phase in the CMC model. Retention components by the SH- SY5Y/CMC model were collected and active components then analyzed by SH-SY5Y/CMC under the optimized conditions. After investigating the suitability and reliability of the SH-SY5Y /CMC method using risperidone, sertraline and clozapine as standard compounds, this method was applied in screening active components from the extracts of TCMs such as Radix Gentianae, Radix Bupleuri, stir-baked semen ziziphi spinosae, rehmannia dride rhizome, uncaria rhynchophylla. Retention components from the extracts in the SH-SY5Y/CMC model were gentiopicrin and rosmarinci acid identified by the GC/MS method. In vitro pharmacological trials indicated that gentiopicrin and rosmarinci acid could concentration dependently protect the SH-SY5Y pre-treated by H2O2 (P < 0.05). The SH-SY5Y/CMC method is an effective screening system that can rapidly detect target components from a complex sample for antipsychotic candidate drug.
The main aim of the present studies is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorder in the depressed and clinically remitted status respectively.
Three groups of bipolar I (n = 92), bipolar II (n = 131) and unipolar depression patients (n = 293) were tested with a battery of neuropsychological tests at baseline and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance.
At the acute depressive state, the three patients groups (bipolar I, bipolar II and unipolar depression) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not attention compared with controls. And post comparisons revealed that bipolar I patients performed significantly worse in these impaired cognitive domain than bipolar II and unipolar depression patients in verbal fluency and executive function. After treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory in relative to controls, while remitted unipolar depression patients showed cognitive impairment in executive function in addition to processing speed and visual memory.
Bipolar I, bipolar II and unipolar depression patients have a similar pattern of cognitive impairment during the state of acute depressive episodes. At the clinically remission, still both bipolar disorder and unipolar depression patients showed cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for unipolar depression
The association between gray matter and cognitive dysfunction in young major depression remains unclear.
To investigate the brain gray matter and the correlation with cognitive function in first-episode, treatment-naive patients with major depressive disorder (MDD).
To explore brain structural pathological mechanisms of cognitive impairment in MDD.
46 MDD aged 18-45 year and 46 controls were assessed by Wisconsin Card Sorting Test (WCST) and Trail making test (TMT). Then, 30 patients and 30 controls were obtained by MRI scan.
The total number of errors, number of preservative errors, random errors of WSCT in MDD were significantly more than that in controls, and the completion time in the TMT-A and TMT-B was longer than that in controls. MDD showed significant less gray matter volumns than controls in frontal lobe (right precentral gyrus, bilateral superior frontal gyrus and right middle frontal gyrus), parietal lobe (left postcentral gyrus, left paracentral lobule, and bilateral precuneus), temporal lobe (right superior temporal gyrus), and occipital lobe (left superior occipital gyrus). There was a significant negative correlation between left postcentral gyrus and left superior occipital gyrus gray matter density and the TMT-B completion time (r=-0.462, P=0.017; r=-0.448, P=0.022).
The first-episode MDD patient exhibiteded cognitive impairment and showed significant lower gray matter density than controls in frontal lobe, parietal lobe, temporal lobe, occipital lobe. Decreased gray matter density in left postcentral gyrus and left superior occipital gyrus may be involved in the executive dysfunction.
The main aim of this study is to investigate the capacity of a number of variables from four dimensions (clinical, psychosocial, cognitive and genetic domains) to predict the antidepressant treatment outcome, and combined the predictors in one integrate regression model with the aim to investigate which predictor contributed most.
In a semi-naturalistic prospective cohort study with a total of 241 fully assessed MDD patients, decrease in HAM-D scores from baseline to after 6 weeks of treatment was used to measure the antidepressant treatment outcome.
The clinical and psychosocial model (R2 = 0.451) showed that HAM-D scores at baseline and MMPI-2 scale paranoia was the best clinical and psychosocial predictor of treatment outcome respectively. The cognitive model (R2 = 0.502) revealed that combination of better performance on TMT-B test and worse performance on TOH and WAIS-R Digit Backward testes could predict decline in HAM-D scores. The genetics analysis only found median of percent improvement in HAM-D scores in G-allele of GR gene BclI polymorphism carriers (72.2%) was significant lower than that in non-G allele carriers (80.1%). The integrate model showed that three predictors, combination of HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, explained 57.1% of the variance.
Three markers, HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, might serve as predictor of antidepressant outcome in daily psychiatric practice.
Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.
The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.
CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.
The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.
Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.
In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.
Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.
11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.
The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.