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Major depressive disorder (MDD) is a common psychiatric disorder that is characterized by cognitive deficits and affective symptoms. To date, an increasing number of neuroimaging studies have focused on emotion regulation and have consistently shown that emotion dysregulation is one of the central features and underlying mechanisms of MDD. Although gray matter morphological abnormalities in regions within emotion regulation networks have been identified in MDD, the interactions and relationships between these gray matter structures remain largely unknown. Thus, in this study, we adopted a structural covariance method based on gray matter volume to investigate the brain morphological abnormalities within the emotion regulation networks in a large cohort of 65 MDD patients and 65 age- and gender-matched healthy controls. A permutation test with p < 0.05 was used to identify the significant changes in covariance connectivity strengths between MDD patients and healthy controls. The structural covariance analysis revealed an increased correlation strength of gray matter volume between the left angular gyrus and the left amygdala and between the right angular gyrus and the right amygdala, as well as a decreased correlation strength of the gray matter volume between the right angular gyrus and the posterior cingulate cortex in MDD. Our findings support the notion that emotion dysregulation is an underlying mechanism of MDD by revealing disrupted structural covariance patterns in the emotion regulation network.

Background: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. Objective: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). Methods: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. Results: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). Conclusions: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD.

Background To identify different network-symptom relationship may be a model of how precision medicine approach. In the July 2019 issue of AJP, Brady et al. successfully identified a network biomarker of negative symptom severity in a sample of patients with schizophrenia using resting state functional connectivity (FC) fMRI, which pushed forward the psychiatric research from purely correlational studies. As we known, medications and different episodes of the disease affect the brain function, so the breakdown of cerebellar-prefrontal network connectivity may not directly correspond to negative symptom. At this point, we would strengthen empirical support for a causal relationship between dysfunctional connectivity and psychopathology using different stages of patients with schizophrenia. Methods We used three independent cohorts with schizophrenia, one of which is 54 medication-naïve patients with first episode schizophrenia (FES) in Shanghai Mental Health Center (SH), the other is 112 medicated patients with FES in Guangzhou Huiai Hospital (GZ1), and the third is 35 chronic patients with schizophrenia in Guangzhou Huiai Hospital (GZ2). All patients were Mandarin-speaking Han Chinese and met the criteria for schizophrenia disorder based on the structured clinical interview for DSM-IV-TR. Negative symptom severity was assessed with the Scale for Assessment of Negative Symptoms (SANS) in SH cohort and with the Positive and Negative Syndrome Scale (PANSS) in GZ1 and GZ2 cohorts. MRI imaging was respectively conducted on Siemens 3.0-T (SH) and Philips 3.0-T (GZ1+GZ2) MRI systems. MRI data were preprocessed and analyzed using the DPABI toolbox, which are the same as the study of Brady et al. Furthermore, we selected the regions of interest (ROI) from the results of Brady et al. for our ROI-wise functional connectivity analysis: right dorsolateral prefrontal cortex (dlPFC, 36, 24, 30), left dorsolateral prefrontal cortex (-33, 30, 42) and midline cerebellar cortex (-9, -96, -27). Results We modeled the effect of negative symptom severity on FC between left or right dlPFC and midline cerebellar cortex while covaried the effects of head motion, age and sex. Our results showed that FC between right dlPFC and cerebellar cortex positively correlated with negative symptom severity in medication-naïve patients (SH cohort: r = 0.343, p = 0.014) and the FC tended to be significantly positively correlated with negative symptom severity in medication patients with FES (GZ1 cohort: r = 0.179, p = 0.061). However, in chronic patients with schizophrenia, the FC between right dlPFC and cerebellar cortex negatively correlated with negative symptom severity (GZ2 cohort: r = -0.390, p = 0.021). The FC between left dlPFC and cerebellar cortex did not correlate with negative symptom severity in all three cohorts. Discussion Our data of chronic patients with schizophrenia validated Brandy’s findings: negative symptom severity was found inversely correlated with FC between right dlPFC and cerebellar cortex. However, our results showed a significantly positive correlation in medication free cohort, and the significance become weaker in the medicated cohort. Our finding proved that the prefrontal cortex – cerebellum network circuit linked directly to negative symptoms, further it is a positive correlation in FES patients, and it is a negative correlation in chronic patients which are the same as Brandy’s. We speculate that medication affects function of the brain network, and then reverses the correlationship between it and the symptoms. We will follow up our two cohorts of FES patients for further fMRI data collection and symptom assessment, and test whether the network could correspond to negative symptom severity.

Background Suicidal ideation (SI) is common in patients with major depressive disorder (MDD) and often related to cognitive deficits. Limited longitudinal study has shown that cognitive improvement is associated with reduced SI. However, the comparatively study in Chinese depressed patients is still absent. The objective of this study was to explore the specific cognitive deficits in Chinese MDD with SI and investigate the relationship between changes in cognition and change in SI across antidepressant treatment. Methods Three hundred and five patients with MDD received four weeks of antidepressant treatment. The 17-item Hamilton Depression Rating Scale (HAMD-17) and four domains of the MATRICS Consensus Cognitive Battery (MCCB), including speed of processing, working memory, visual learning and verbal learning were measured at baseline and four-week follow-up. Results One hundred and thirty patients (42.6%) expressed suicidal ideation. Suicidal patients performed worse on verbal learning than non-suicidal patients. Change in speed of processing domain was negatively associated with change in suicidal scores over time. Logistic regression analysis showed that reduction of SI was associated with improvement of speed of processing. Limitation The major limitation was that there was no healthy control group in the current study, which might limit the interpretation of cognitive deficits in depressed patients with SI. Conclusions Our findings suggest that suicidal patients performed worse on verbal learning which can potentially serve as a cognitive biomarker of suicide risk in MDD. Moreover, reduced suicidal ideation was associated with improved speed of processing.

Objective Preclinical studies have reported that abnormal kynurenic acid (KYNA) may play a role in cognitive deficits. Schizophrenia (SCZ) is characterized by a wide range of cognitive deficits that may evolve from abnormal KYNA. This study aimed to explore the relationship between KYNA and cognitive impairment in SCZ, which has not yet been reported. Methods We recruited 30 SCZ patients and 34 healthy controls, measured clinical symptoms by using the Positive and Negative Syndrome Scale and performed cognitive tests using the MATRICS Consensus Cognitive Battery (MCCB). Plasma levels of tryptophan, kynurenine, and KYNA were determined by high-performance liquid chromatography–tandem mass spectrometry. Results We found that plasma KYNA levels were significantly higher in patients than in healthy controls (p=0.009). The cognitive performance of patients in the total MCCB scores and the scores of all subscales were significantly lower than those in healthy controls (all P < 0.01). Correlation analysis showed that KYNA levels were negatively correlated with attention/vigilance (r=–0.457, p=0.019) and social cognition (r=–0.481, p=0.013) only in SCZ patients. Conclusion Our results indicate that elevated plasma KYNA levels may serve as a biomarker of cognitive impairment in SCZ patients.

BACKGROUND Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. OBJECTIVE To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). METHODS The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naive AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. RESULTS 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p

Background Ketamine has rapid-acting antidepressant and antisuicidal properties, while a proportion of patients do not adequately achieve a complete response to ketamine. Our aim was to explore the applicability of using clinical factors and serum tryptophan (TRP) metabolites to predict the response to six doses of ketamine for depression with suicidal ideation. Methods Seventy-three depressed patients with suicidal ideation received a thrice-weekly infusion regimen of subanaesthetic doses of ketamine. Clinical symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Scale for Suicide Ideation (SSI) and Patient Health Questionnaire-9 (PHQ-9), and serum levels of TRP, kynurenine (KYN) and kynurenic acid (KYNA) were detected by liquid chromatography-tandem mass spectrometry at baseline and day 1 (1 day after the first infusion). The potential predictors of response was evaluated using receiver operating characteristic (ROC) curve analyses. Results The area under the curve (AUC = 0.959) implied a good accuracy of the combination of early clinical response and day 1 KYN and KYNA levels as a predictor of acute antidepressant response. The combination of early clinical response and day 1 KYNA levels showed moderate discrimination of acute antisuicidal response with an AUC of 0.825 and short-term antidepressant response with an AUC of 0.813. Limitations The patients continued receiving previous medications during ketamine treatment, which may have impacted the TRP metabolites. Conclusion The combination of early clinical response and TRP metabolites at the early stage of repeated ketamine treatment could be considered an eligible predictor for acute- and short-term response for treating depression with suicidal ideation.

BACKGROUND Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²₁ = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (β = 0.75, t = 7.72, P < .001) and total score (β = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (β = 0.74, t = 8.45, P < .001), total score (β = 0.47, t = 5.71, P < .001), and cognitive factor subscore (β = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

There is evidence that obesity or higher body mass index is correlated with cognitive impairment in schizophrenia. Recent studies have demonstrated that genetic risk factors, such as the NRG3, are correlated with both elevated BMI and reduced cognitive function. In present study, we aimed to determine whether possession of the NRG3 rs10748842 influences the correlation between elevated BMI and reduced cognitive ability in schizophrenia. To our knowledge, this has never been examined before. A total of 625 inpatients with schizophrenia and 400 controls were recruited. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. We used multiple analysis of covariance (MANCOVA), analyses of covariance (ANCOVA), Pearson correlations, partial correlations, and multivariate regression analysis to test the influence of NRG3 rs10748842 on the aforementioned variables. All RBANS five sub-scores and total score were lower in patients than those in controls (all p NRG3 rs10748842 TC + CC heterozygous genotype had lower attention score compared to TT homozygous genotype (adjusted F = 4.77, p = 0.029). BMI was positively associated with language score in patients (β = 0.387, t = 2.59, p = 0.01). Interestingly, we further found positive association between BMI and language score in TT carriers (partial correlations: r = 0.13, adjusted p = 0.004; multivariate regression: β = 0.42, t = 2.66, p = 0.008), but not in CT + CC carrier (p > 0.05). Our study demonstrated that NRG3 rs10748842 was associated with cognitive impairments, especially attention performance in schizophrenia. Moreover, NRG3 rs10748842 altered the effect of BMI on cognitive impairments as measured by the RBANS language score in chronic patients with schizophrenia.

Objective Ketamine has been demonstrated to have robust and rapid antidepressant effects, and few studies have focused on the relationship between insomnia and the efficacy of ketamine. The objective of this study was to examine whether baseline insomnia predicted the antidepressant efficacy of repeated intravenous ketamine infusions for unipolar and bipolar depression. Method Patients with high insomnia (n = 64) or low insomnia (n = 68) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Monday-Wednesday-Friday). The Montgomery-Asberg Depression Rating Scale (MADRS) without sleep item was used to assess depressive symptoms. Response was defined as a MADRS total score ≥ 50%, and remission was defined as a MADRS total score ≤ 10. Result There were no differences in response or remission rates between patients with high and low insomnia. However, the logistic regression model showed that high insomnia predicted an increased likelihood of response and remission. Cox proportional hazards models showed a reduced latency to respond and remit in patients with high insomnia. A linear mixed model showed that the high insomnia subgroup had greater improvement than the low insomnia subgroup (all p Limitation The major limitation of this study is the open-label design. Conclusion When given six ketamine infusions, patients with high insomnia were more likely to respond and remit than those with low insomnia. Patients with high insomnia showed not only a shorter latency to respond and remit, but also greater improvement than those with low insomnia.

Objectives:This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD).Methods:A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias.Results:Sixteen RCTs ( n=1357) on minocycline (50–300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: −0.45 (95%CI: −0.73, −0.16), p=0.002; I2=77%], positive [SMD: −0.15 (95%CI: −0.28, −0.02), p=0.02; I2=0%], negative [SMD: −0.62 (95%CI: −0.95, −0.28), p=0.0003; I2=85%] and general psychopathology scores [SMD: −0.28 (95%CI: −0.53, −0.03), p=0.03; I2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache ( p=0.02, number-needed-to-harm=14, 95%CI=5–14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category.Conclusion:In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated.Review registration:PROSPERO: CRD42018102483

Aim The aim of the present study was to evaluate the efficacy and safety of lurasidone for the treatment of Chinese schizophrenic patients. Methods Hospitalized schizophrenia patients aged 18-65 were randomized to 6 weeks of double-blind, double-dummy, flexible-dose treatment with lurasidone (40 or 80 mg/day) or risperidone (2, 4 or 6 mg/day). Efficacy was evaluated using a non-inferiority comparison of lurasidone relative to risperidone based on week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score. Safety assessments included adverse events, clinical laboratory measures, and electrocardiograms. Results Four hundred and forty-four patients were screened to obtain an intent-to-treat sample of 384 patients, of whom 54 patients discontinued treatment prior to 6 weeks. Lurasidone met the criteria for non-inferiority versus risperidone on the PANSS total score. Adjusted mean (SE) change at week 6 on the PANSS total score was -31.2 (1.0) and -34.9 (1.0) in the lurasidone and risperidone group, respectively. The mean difference score was 3.7, and the upper boundary of the 95%-confidence interval (1.0-6.3) was less than the prespecified margin of 7.0. No clinically meaningful between-treatment group differences were evident on secondary efficacy measures, including PANSS positive, PANSS negative, Clinical Global Impression scale - Severity, and Calgary Depression Scale for Schizophrenia scales. The incidence of adverse events was lower for lurasidone vs risperidone for extrapyramidal symptoms (17.0% vs 38.2%), akathisia (7.2% vs 13.6%), prolactin increase (3.1% vs 14.1%), and weight increase (0.5% vs 5.2%). Conclusion Lurasidone was found to be non-inferior to risperidone on the primary endpoint with minimal effects on weight, metabolic parameters, or prolactin levels.

Although estrogenic fluctuation is considered a major risk factor for postpartum depression (PPD), the effects of the interactions between the genetic background and estradiol (E2) change on PPD are not well understood. Here, a cohort study with 437 postpartum women was carried out to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and E2 change on the risk of PPD symptoms. The participants were assessed using the Edinburgh Postnatal Depression Scale and the Self-Rating Depression Scale at 1 and 6 weeks after delivery. The PCR-based restriction fragment length polymorphism method was utilized to examine the genotype distribution of the 5-HTTLPR polymorphism, and the serum levels of E2 were determined in individuals in the third trimester of pregnancy and at 1 week postpartum. A significant association was observed between E2 change and PPD susceptibility in the late postpartum period (6 weeks) [P = 0.002, odds ratio (OR) = 2.341, 95% confidence interval (CI) = 1.361-4.027], but it was not observed in the early postpartum period (1 week). There was no significant association between the 5-HTTLPR genotype and PPD risk at both the early and late postpartum periods (P0.05). However, the interaction between E2 change and the 5-HTTLPR polymorphism could reasonably influence PPD risk. The women who carried the SS genotype with large decreases in E2 showed a significantly higher risk for PPD at both the early (P = 0.002, OR = 2.525, 95% CI = 1.384-4.059) and late postpartum periods (P0.001, OR = 3.108, 95% CI = 1.562-4.436) compared with those who carried the SL/LL genotype. This study suggests that there is an association between E2 change in the perinatal period with the 5-HTTLPR genotype and the occurrence of PPD.

BackgroundSchizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.AimsTo investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.MethodGenomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.ResultsThe imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.ConclusionsThese findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.

Aim Olfactory deficits are potential markers of early diagnosis, monitoring progress and predicting outcome in patients with schizophrenia and depression. We aimed to investigate differences in patterns and influencing factors of olfactory deficits between patients with acute episode of schizophrenia and major depressive episode (MDE). Methods Fifty-two patients with acute episode of schizophrenia, 75 patients with unipolar MDE and 199 healthy controls were included in this retrospective study. Following a structured interview, participants underwent olfactory tests (Sniffin' Sticks), assessment of psychiatric symptoms (Positive and Negative Syndrome Scale), depressive symptoms (Hamilton Depression Rating Scale), and cognitive function (color-word test and word generation test). Results Both patients with schizophrenia and MDE exhibited significant olfactory deficits, and MDE patients have poorer olfactory sensitivity than schizophrenia. Patients with MDE had a higher proportion of olfactory deficits (45.3% and 28%, respectively) but a better self-awareness (21.3% and 9.6%, respectively) than patients with schizophrenia. In patients with schizophrenia, PANSS scores was positively associated with olfactory sensitivity but negatively associated with olfactory identification, and olfactory discrimination was associated with word generation. In patients with MDE, olfactory discrimination was associated with word generation and age, but not disease severity. First-episode schizophrenia group showed significantly lower threshold scores than recurrent schizophrenia group, and first-episode MDE group had significantly lower threshold scores and higher discrimination scores than the recurrent MDE group. Conclusions Patterns and modulating factors of olfactory deficits in acute episode of schizophrenia and MDE are different, their differences should be considered when using olfactory deficits as marker in clinical practice.

Recent studies have suggested that neurocognition is changed after repeated infusions of ketamine in patients with treatment-resistant depression (TRD). The objective of this study was to investigate whether differences existed in the neurocognitive effect of six ketamine infusions in patients with anxious and nonanxious TRD and to determine the association between baseline neurocognition and changes in symptoms after the infusions.Patients with anxious (n = 30) and nonanxious TRD (n = 20) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days. Speed of processing (SOP), working memory (WM), verbal learning and memory (VBM), visual learning and memory (VSM) and the severity of depressive and anxious symptoms were assessed at baseline, one day after the last infusion (day 13) and two weeks after the completion of the serial infusions (day 26). A linear mixed model was used to determine whether the neurocognitive changes differed between the two groups. Pearson correlation analysis was used to determine the relationship between baseline neurocognition and the changes in the symptomatic scores.Patients with anxious TRD had significant increases in SOP on day 13 and day 26 (both p 0.001), and in VBM on day 13 (p = 0.028). However, no significant increase in any neurocognitive domain was found in patients with nonanxious TRD. Faster SOP at baseline was associated with greater improvement of anxious symptoms in patients with anxious TRD, and better VSM at baseline was associated with greater improvement of depressive symptoms in patients with nonanxious TRD.The major limitation of this study is the open-label design.After six ketamine infusions, neurocognitive improvement was observed in patients with anxious TRD but not in patients with nonanxious TRD.

Background Suicide is a tremendous public health crisis and is demanded urgent intervention. Previous studies found that ketamine intervention could rapidly reduce suicidal ideation in depression. However, the comparatively study in Chinese population remains absence. The current study aims to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal patients, especially distinguish between low suicidal ideation (SI) group and high SI group. Methods Eighty-six unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) and Beck Scale for Suicide Ideation (SSI) was measured at baseline, 4 h and 24 h after each infusion, and two-week naturalistically follow-up. Results Forty-nine (57.0%) patients relief of suicidal ideation after first infusion and 56 (65.1%) after six infusions. Anti-suicidal response rate in low SI group were higher than high SI group, and anti-suicidal response at 4 h after first infusion was significant predictor of response at 24 h after sixth infusion. Furthermore, at 24 h after the sixth infusion, correlation between changes in suicidal ideation and depression was 0.23, accounting for 7.4% in the variance of suicidal ideation change. Limitation The major limitation of this study was that lack of a placebo or other control group limits the interpretation of efficacy. Conclusions We confirmed that six repeated ketamine infusions for Chinese suicidal depressed patients were effective in generating a rapid response of suicidal ideation, especially low SI achieved more benefits from ketamine infusions.

Evidence has shown the importance of tumor necrosis factor alpha (TNF-alpha) in the pathophysiological feature in schizophrenia patients. This study aims to determine the impact of a single-nucleotide polymorphism (SNP) in the TNF-alpha gene promoter on the susceptibility, onset age, and cognitive function of schizophrenia.The SNP -1031TC in the TNF-alpha gene was genotyped in 905 patients and 571 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the schizophrenia symptoms and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognitive function.There was no significant difference in allele or genotype distribution of the SNP -1031TC between patients and controls (p = .85, p = .98). This polymorphism had no significant genotypic effect on the symptomatology assessed by the PANSS. Interestingly, this polymorphism was significantly correlated with onset age in schizophrenia patients (p = .004). We found an earlier onset age in patients with the TT genotype compared to those with the CT and CC genotypes (both p.05). Moreover, there were significant genotypic effects on the immediate memory index, visuospatial/constructional index, and RBANS total score (all p0.05) in the patient group.Our results suggest that the SNP -1031TC of the TNF-alpha gene may not be associated with susceptibility to schizophrenia but possibly acts as a modulator for its onset age as well as for cognitive deficits. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder. Methods: Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday–Wednesday–Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively. Results: After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, pConclusion: Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the "Sniffin' Sticks" olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

Background: Bilirubin may be an upstream activator inducing Alzheimer's disease (AD). Methods: Bilirubin/albumin (ALB) levels in dementia patients with Aβ deposition were explored. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was prescribed to AD patients to examine the effect of albumin on AD symptoms. Findings: Significantly higher indirect bilirubin (IBIL) levels and higher ratio of IBIL to albumin (IBIL/ALB) were reported in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies and general paresis of insane.Intravenous albumin significantly lowered the ratio of IBIL to albumin (IBIL/ALB) at week 24. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve show significantly improvements in change of Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale scores and Clinical Dementia Rating Scale-Sum of Boxes scores. Interpretation: IBIL and IBIL/ALB was significantly higher in dementia patients with Aβ deposition. Bilirubin may be an upstream activator that induces AD. Consistent with these clinical findings, our intervention study shows that increasing serum bilirubin binding capacity from albumin by intravenous supplementation of human albumin yields benefit on daily function and dementia severity in AD patients. Targeting IBIL/ALB has highly potential for AD treatment. Trial Registration: The study was registered at chictr.org.cn (ChiCTR-IOR-17011539). Funding Statement: This work was supported by the National Funds for Developing Local Colleges and Universities (B16056001), Natural Science Foundation research team of Guangdong Province (2018B030312001) (to J.L), and Guangdong Natural Science Foundation (2017A030313662), Science and Technology Program of Guangzhou (201707010046) (to C.Z). Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: The Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital) approved this study. A written informed consent was obtained from the participants or their nearest relatives.

The objective of this study was to investigate the effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with schizophrenia using EEG microstates. Thirty-eight patients with chronic schizophrenia were included in a double-blind, randomized and sham-controlled trial (19 participants in the active group and 19 participants in the sham group) and received 10 Hz active or sham rTMS stimulation to the left dorsolateral prefrontal cortex (left DLPFC) 5 days per week over for 4 weeks. Four classical microstate classes (i.e., classes A, B, C and D) were identified by clustering, and the parameters (i.e., duration, occurrence and contribution) of each class were computed. Our results showed that (1) after stimulation, the positive and negative syndrome scale (PANSS) positive scores decreased significantly in the active group; (2) the duration of the microstate of class C derived from EEG data decreased significantly in the active group; and (3) the change of the duration of class D in the active group was significantly higher than that in the sham group. Our findings demonstrated that 10 Hz active rTMS stimulation was beneficial to improving the positive symptoms of patients with chronic schizophrenia, and the EEG microstate could be an effective indicator of symptom improvements.

NiCrAlO/Al2O3 solar selective coating prepared by direct current (DC) magnetron sputtering and water boiling is demonstrated in this paper. Firstly, the coating consisting of tandem layers of Au/NiCrAl/Al with different NiCr volume fractions in NiCrAl sublayers is deposited solely by DC magnetron sputtering. Then the coating is boiled by deionized water and dehydrated by vacuum heating. The surface morphology, the depth distributions and relative chemical states of elements of the coating are characterized by scanning electron microscopy (SEM), Auger electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS). It is found that Al in the coating is totally oxidized while most of NiCr and Au keep metallic after water boiling and vacuum dehydration, which forms the effective solar selective coating consisting of Au/NiCrAlO/Al2O3 with different metallic NiCr volume fractions. High near normal solar absorptance of 0.964 and low near normal thermal emittance of 0.066 are demonstrated by the reflectance measured by UV-VIS-IR spectrometer. The combination of DC magnetron sputtering and water boiling is very promising for fabrication of solar selective coating based on the dielectric aluminum oxide, as it is environmentally friendly and circumvents the radio frequency (RF) magnetron sputtering which needs RF automatic matching.

In recent years, finding photocatalysts that can operate at a broad range of wavelengths is interesting in photocatalytic research field. In this study, CsxWO3/BiOCl composites with different mass ratios of CsxWO3 were synthesized by solid state calcination method. The as-prepared samples were characterized by X-ray diffraction analysis, scanning electron microscopy, photoluminescence emission spectroscopy, photocurrent and UV–vis. diffuse reflectance spectra. The photocatalytic activity of the products was evaluated through photocatalytic degradation of rhodamine B (RhB) and methylene blue (MB) under visible light irradiation. The results show that the photocatalytic activity of the CsxWO3/BiOCl composite photocatalyst with the mass ratio 1/3 is better than the single CsxWO3 and BiOCl. The significantly improved photocatalytic activity is attributed to the synergetic effect of two semiconductors, such as the extended visible absorption and the promoted electron–hole pairs separation. The novel composite photocatalyst will have a great application potential in the field of environmental purification.

BackgroundUnder ‘cocktail party’ listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking.MethodUsing functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions.ResultsIn both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients.ConclusionsThe left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.

Caregiver burden may be especially high in China. However, there has been no empirical study comparing burden experienced by caregivers who live with their patient kin and caregivers live separately from their kin. This study compared caregiver burden in cohabiting and non-cohabiting families and examined characteristics that may account for observed differences ion experienced burden. Patients were evaluated on symptoms, insight, attitudes toward medication before discharge and their prime caregivers were evaluated on family burden shortly after admission. Bivariate analysis of covariance and multiple regression analyses were used to compare burden between these two groups and to identify factors that might account for observed differences between them. Of 243 schizophrenic patients, 4.9% lived with their primary caregivers. Caregiver burden was greater among caregivers living with patient kin on three factors, caregiver distress, disrupted routines and assistance provided by caregivers, but not on caregiver perceptions of behavioral problems or suicidality. Multiple regression analysis showed that living with caregiver explained 6.7%, 8.3% and 6.7% of the variance in distress, disrupted routines and helpfulness. Living with a patient was by far the strongest correlate of increased burden experienced by schizophrenia caregivers in this study and these caregivers should be offered community-based support.

P-glycoprotein (Pgp) overexpression in the blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Recently, the poly(butylcyanoacrylate) (PBCA) nanoparticle system was shown to overcome the obstacle of the BBB to deliver drugs into the brain. To determine whether pluronic P85-coated phenytoin poly(butylcyanoacrylate) nanoparticles (P85-PHT-PBCA-NPs) target PHT to the brain, PHT-resistant rats overexpressing Pgp in the BBB were screened by response to PHT treatment after chronic temporal lobe epilepsy induced by lithium-pilocarpine, followed by direct verification of PHT transport via measurement of brain PHT concentrations using microdialysis. Thereafter, the PHT-resistant rats were divided into three groups, which were treated with PHT, PHT + tariquidar (TQD), or P85-PHT-PBCA-NPs. PHT + TQD and P85-PHT-PBCA-NPs showed anticonvulsant activity in the PHT-resistant rats and increased the ratio of the area under the curve of the PHT concentrations in the brain/plasma in comparison with that observed in animals subjected to PHT treatment. However, the ratios of the PHT concentrations in the liver/plasma and kidney/plasma following P85-PHT-PBCA-NPs treatment were much lower than those measured following PHT + TQD treatment. Thus, Pgp overexpression decreases therapeutic drug concentrations in the brains of subjects with drug-resistant epilepsy and P85-PHT-PBCA-NPs could increase these drug concentrations.

Objective Although concern about chronic ketamine abuse has grown, the characteristic symptomatology of chronic ketamine users has yet to be examined. This study aims to measure the psychotic, depressive and anxiety symptoms in chronic ketamine users. Methods A group of chronic ketamine users in Guangzhou, China were evaluated. The socio-demographic and drug use characteristics of subjects were documented. Symptoms of psychosis, depression, anxiety were evaluated by the Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The severity of the symptoms was identified by standard severity cutoffs. Results The PANSS total score, positive symptom, negative symptom, general psychopathology subscale score were 45.3±8.4, 8.0±1.7, 13.2± 3.9 and 24.2± 4.9 respectively. BDI and BAI score was 13.1±6.5 and 15.7±9.6 respectively. 77.5% and 46.0% of the subjects showed moderate to severe depressive symptoms and anxiety symptoms respectively. The BDI score was positively correlated with ketamine use frequency. The BAI score was positively correlated with ketamine use frequency. Conclusions Depressive symptoms were commonly presented in chronic ketamine users. The higher ketamine use frequency and dosage were associated with more severe depressive symptoms.

NiCr–MgF2 spectrally selective solar absorber, which consists of the tandem films of Au, high-metal-volume-fraction (HMVF) NiCr–MgF2, low-metal-volume-fraction (LMVF) NiCr–MgF2 and MgF2, is designed and fabricated for ultra-high solar absorptance and low thermal emittance. The performance of Au/NiCr–MgF2 (HMVF)/NiCr–MgF2 (LMVF)/MgF2 is simulated using the effective medium theory and film matrix method, and the optimized NiCr–MgF2 spectrally selective solar absorber has a normal solar absorptance (αsn) of 0.981 and a normal thermal emittance (en) of 0.042 at 25 °C. The tandem films of Au/NiCr–MgF2 (HMVF)/NiCr–MgF2(LMVF)/MgF2 are fabricated by magnetron sputtering and measured by UV-VIS-IR spectrometer, and it has an ultra-high near normal solar absorptance of αsn = 0.976 and a low near normal thermal emittance of en = 0.045 at 25 °C, which approaches very closely to the simulated limit. Furthermore, NiCr–MgF2 spectrally selective solar absorber allows a wide incident angle (θ) with its angular solar absorptance αs(θ)≥0.957 and angular thermal emittance e(θ)≤0.054 if θ ≤ 50°. Such spectrally selective solar absorber is an outstanding candidate for solar thermal applications.

Background: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation. Methods: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery–Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days. Results: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p Conclusion: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation.

Fengchun Wu,1,2,* Yue Zhang,2,3,* Yongzhe Yang,2–4 Xiaobing Lu,1,2 Ziyan Fang,1 Jianwei Huang,1 Lingyin Kong,3 Jun Chen,5,6 Yuping Ning,1,2 Xiaobo Li,7,8 Kai Wu2,3,5,6,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; 2Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China; 3Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, China; 4School of Medicine, South China University of Technology (SCUT), Guangzhou, China; 5Guangdong Engineering Technology Research Center for Diagnosis and Rehabilitation of Dementia, Guangzhou, China; 6National Engineering Research Center for Healthcare Devices, Guangzhou, China; 7Department of Biomedical Engineering, New Jersey Institute of Technology, NJ, USA; 8Department of Electric and Computer Engineering, New Jersey Institute of Technology, NJ, USA; 9Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan *These authors contributed equally to this work Background: Structural and functional brain abnormalities in schizophrenia (SZ) have been widely reported. However, a few studies have investigated both structural and functional characteristics in SZ patients at different stages to understand the neuropathology of SZ. Methods: In this study, we recruited 44 first-episode drug-naive SZ (FESZ) patients, 44 medicated chronic SZ (CSZ) patients, and 56 normal controls (NCs) and acquired their structural and resting-state functional magnetic resonance imaging (MRI). We then made group comparisons on structural and functional characteristics, including regional gray matter volume (GMV), regional homogeneity, amplitude of low-frequency fluctuation, and degree centrality. A linear support vector machine (SVM) combined with a recursive feature elimination (RFE) algorithm was implemented to discriminate three groups.Results: Our results indicated that the regional GMV was significantly decreased in patients compared with that in NCs; CSZ patients have more diffused GMV decreases primarily involved in the frontal and temporal lobes when compared with FESZ patients. Both FESZ and CSZ patients showed significant functional alterations compared with NCs; when compared with FESZ patients, CSZ patients showed significant reductions in functional characteristics in several brain regions associated with auditory, visual processing, and sensorimotor functions. Moreover, a linear SVM combined with a RFE algorithm was implemented to discriminate three groups. The accuracies of the three classifiers were 79.80%, 83.16%, and 81.71%, respectively. The performance of classifiers in this study with multimodal MRI was better than that of previous discriminative analyses of SZ patients with single-modal MRI.Conclusion: Our findings bring new insights into the understanding of the neuropathology of SZ and contribute to stage-specific biomarkers in diagnosis and interventions of SZ. Keywords: multimodal MRI, schizophrenia, support vector machine, SVM, classification

Background Adjunctive ketamine with electroconvulsive therapy (ECT) has been investigated for treating major depressive disorder (MDD), but the findings have been inconsistent. Aim This is an updated meta-analysis of the efficacy and safety of ketamine augmentation of ECT in the treatment of MDD. Methods Randomized controlled trials (RCTs) reporting on the efficacy and safety of ketamine and ECT were identified and analyzed. Results Seventeen RCTs (n = 1,035) compared ketamine alone or ketamine plus other anesthetic drugs (n = 557) with other anesthetic agents (n = 478) in MDD patients who received ECT. Ketamine+other anesthetic drugs was superior in improving depressive symptoms over other anesthetic medications at early study time point, but not at post-ECT or end of study time points. Ketamine alone was not more efficacious in treating depressive symptoms than other anesthetic drugs at early study, post-ECT and end of study time points. Sensitivity analysis and 19 of the 20 subgroup analyses also confirmed the lack of significance of these findings. Eleven RCTs testing the effects of ketamine on neurocognitive functions with various test batteries found mixed results. Ketamine alone significantly increased blood pressure more than other anesthetic drugs in MDD treated with ECT. Conclusion Compared to other anesthetic agents, ketamine alone does not appear to improve the efficacy of ECT. However, ketamine+other anesthetic combinations may confer a short-term advantage in improving depressive symptom at the early stages of ECT.

A new self-rating functional scale (SRFS) was developed to assess the functionality of patients with schizophrenia, referred to the structure of Personal and Social Performance Scale (PSP). The main aim of this study was to evaluate the reliability and validity of the SRFS. A total of 210 patients with schizophrenia were recruited from outpatient clinics in six sites in China. Demographic information, SRFS, PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale were assessed. Spearman's correlation coefficient and path analysis were used to assess the reliability and validity of the SRFS. Cronbach's α coefficient was used to assess the internal consistency reliability. Cronbach's α was 0.83, and ranged from 0.80 to 0.82 stably, indicating that the scale was reliable in internal consistency. Spearman's correlation coefficient between split two parts was 0.68 (P

Background: Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression. Methods: Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion. Results: Significant improvements were found on speed of processing ( F=9.344, pConclusions: Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.

Ketamine has demonstrated a rapid antidepressant and antisuicidal effect in patients with major depressive disorder (MDD), but the neurocognitive effects of ketamine are relatively unknown. This study aims to examine the neurocognitive effects of six ketamine infusions and the association of baseline neurocognitive function and the change in severity of depressive symptoms after the last infusions.Sixty-four patients with MDD completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) administered over a 12-day period (Monday-Wednesday-Friday), and were followed by a 2-week observational period. Four domains of neurocognitive function (including speed of processing, working memory, visual learning and verbal learning) were assessed using the MATRICS Consensus Cognitive Battery (MCCB) at 0, 13 and 26 days.In linear mixed model, significant improvements were found in terms of speed of processing (F = 20.7, p 0.001) and verbal learning (F = 11.1, p 0.001). The Sobel test showed the improvement of speed of processing (Sobel test = 2.8, p 0.001) and verbal learning (Sobel test = 3.6, p 0.001) were significantly mediated by change in depressive symptoms. Other two neurocognitive domains showed no significant changes over time. Correlation analysis showed no significant association of change in depressive symptoms with neurocognitive function at baseline.Our findings suggest that six ketamine infusions were associated with the improvement of speed of processing and verbal learning, which were partly accounted for by improvement in the severity of depression symptoms over time.

Background Major depressive disorder (MDD) is associated with neurocognitive impairment and reduced social-occupational function. However, neurocognition and social-occupational function in patients with anxious depression have been under-investigated. An increasing number of studies have demonstrated that neurocognition plays an important role in social-occupational function. The objective of this study was to investigate the association of severity of symptoms, neurocognition and social-occupational function in patients with anxious depression. Method Using a cross-sectional design, 214 patients with MDD were recruited consecutively and evaluated using the 17-item Hamilton Depression Rating scale (HAMD-17), the MATRICS Consensus Cognitive Battery (MCCB) and the Global Assessment of Functioning (GAF). Result The prevalence of anxious depression in MDD patients was 64.5%. Compared to non-anxious subjects, the anxious group had more severe symptoms. Moreover, in the anxious group, social-occupational function was associated with several domains of symptoms and neurocognition, while social-occupational function was associated with only one aspect of depressive symptoms (cognitive disturbance) in the non-anxious group. In addition, there was a mediating effect of neurocognition on the association between the severity of symptoms and social-occupational function in the anxious group. Limitations The major limitation of the present study is the use of a cross-sectional design that is unable to illuminate causal relationships. Conclusion Our results suggest that the severity of symptoms is negatively associated with neurocognition and social-occupational function and that neurocognition is positively associated with social-occupational function in patients with anxious depression.

Background: It is well established that patients with chronic schizophrenia have a substantially higher rate of attempted and completed suicide than the general population. However, the actual prevalence of suicide attempts at first-episode psychosis is relatively unknown. Previous studies showed that suicidal schizophrenia patients demonstrate higher cognitive function than nonsuicidal patients, though with inconsistent results. The aims of the study were to examine the prevalence of suicide attempts and the association of this prevalence with demographic and clinical variables and cognitive function in Chinese first-episode, drug-naive (FEDN) schizophrenia patients using a cross-sectional and case-control design. Method: A total of 357 FEDN inpatients meeting DSM-IV criteria for schizophrenia and 380 healthy controls were enrolled and completed a detailed in-house questionnaire. The suicide attempt data were collected from medical records and interviews with the patients and their family members. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to measure cognition in the 28 patients with and 95 patients without a history of suicide attempt and 151 healthy controls. Also, patients were rated on the Positive and Negative Syndrome Scale (PANSS). This study was conducted from June 2013 to December 2015. Results: A suicide attempt rate of 12.0% was found in inpatients with first-episode schizophrenia. The attempters were more likely to smoke (34.4% vs 17.9%; chi(2) = 5.49, P =.019) and had lower severity of negative symptoms (F-1,F-354 = 4.12, P =.043) as compared to FEDN patients without a suicide attempt. All 5 RBANS subscales (all P .05) showed significantly lower cognitive performance for FEDN patients than for healthy controls. Among the FEDN patients, the suicide attempters performed better than nonattempters on attention (F-1,F-121 = 5.12, P =.025), with an effect size of 0.49. The following variables were independently associated with suicide attempt as shown by multivariate regression analysis: PANSS negative symptom subscale score (Wald chi(2)(1) = 7.90 P =.005; adjusted OR = 0.807, 95% CI, 0.696-0.936) and Attention (Wald chi(2)(1) = 4.69, P =.03; adjusted OR = 0.957, 95% CI, 0.918-0.997). Conclusions: FEDN patients with schizophrenia attempt suicide more often than the general population. The suicidal patients were more likely to smoke, had lower severity of negative symptoms, and showed better attention than nonsuicidal patients.

This work presents an automatically annotated fiber cluster (AAFC) method to enable identification of anatomically meaningful white matter structures from the whole brain tractography. The proposed method consists of 1) a study-specific whole brain white matter parcellation using a well-established data-driven groupwise fiber clustering pipeline to segment tractography into multiple fiber clusters, and 2) a novel cluster annotation method to automatically assign an anatomical tract annotation to each fiber cluster by employing cortical parcellation information across multiple subjects. The novelty of the AAFC method is that it leverages group-wise information about the fiber clusters, including their fiber geometry and cortical terminations, to compute a tract anatomical label for each cluster in an automated fashion. We demonstrate the proposed AAFC method in an application of investigating white matter abnormality in emotional processing and sensorimotor areas in major depressive disorder (MDD). Seven tracts of interest related to emotional processing and sensorimotor functions are automatically identified using the proposed AAFC method as well as a comparable method that uses a cortical parcellation alone. Experimental results indicate that our proposed method is more consistent in identifying the tracts across subjects and across hemispheres in terms of the number of fibers. In addition, we perform a between-group statistical analysis in 31 MDD patients and 62 healthy subjects on the identified tracts using our AAFC method. We find statistical differences in diffusion measures in local regions within a fiber tract (e.g. 4 fiber clusters within the identified left hemisphere cingulum bundle (consisting of 14 clusters) are significantly different between the two groups), suggesting the ability of our method in identifying potential abnormality specific to subdivisions of a white matter structure.

Background Suicidal ideation (SI) is a common and serious clinical concern in people with major depressive disorder (MDD). Inconsistent evidence suggests that individuals with SI may have a lower measured intelligence quotient (IQ) than those without SI. The aims of this study were to examine SI prevalence and its associations with demographic, clinical variables and IQ in Chinese drug-naive MDD patients. Methods 488 drug-naive Chinese Han patients (male: 203, 41.6%) meeting a DSM-IV diagnosis of MDD were enrolled in a cross-sectional study involving seven hospitals. All participants were asked to complete a series of questionnaires, which include information on socio-demographic and clinical variables. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Brief Psychiatric Rating Scale (BPRS) were also administered. Verbal IQ (VIQ), performance IQ (PIQ) and full-scale IQ (FIQ) scores were measured using the Chinese version of the Wechsler Adult Intelligence Scale-Ⅲ (WAIS-Ⅲ). We categorized patients with SI based on a cut-off score of ≥3 on HAMD item 3. Results An estimated prevalence 32.8% (160/488) of drug-naive MDD patients experienced SI during the current episode of illness. Patients with SI were more likely to be divorced (x2 = 6.93, p = 0.031), male (x2 = 6.04, p = 0.014), had higher severity of depression and anxiety symptoms (t = −8.14, p Limitations A cross-sectional study which did not assess the influence of severity of SI. Conclusions The prevalence of SI in drug-naive Chinese patients with MDD is high, and associated with marital status, severity of depression, psychotic features and measured IQ. Further research is needed to further explore these and other potentially relevant risk factors which might affect clinical outcomes.

Schizophrenia displays sex differences in many aspects. Decreased brain-derived neurotrophic factor (BDNF) levels have been reported to be associated with high body weight or obesity as well as other psychopathological aspects in schizophrenia patients. This study aimed to explore sex differences in the relationship between serum BDNF levels and obesity in patients with chronic schizophrenia. We recruited 132 Chinese patients with chronic schizophrenia (98 males and 34 females) and compared sex differences in the body mass index (BMI), obesity, serum BDNF levels, and their associations. Psychopathology symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). A regression model with various demographic and clinical variables was applied to predict the serum levels of BDNF. Female patients had a higher rate of obesity and higher BMI, but lower BDNF levels than male schizophrenia patients. A significantly negative correlation was observed between BMI and BDNF levels only in female patients but not in male patients. The multiple regression model with demographic and clinical variables significantly predicted BDNF levels only in female patients, with a medium size effect. And only in female patients, BMI made a significant contribution to this prediction. Our results indicate significant sex differences in the obesity, BMI, BDNF levels, and their association in chronic patients with schizophrenia, showing a significant inverse correlation between BMI and BDNF levels only in female patients. Thus, sex needs to be considered when assessing the relationship between BDNF and metabolic syndromes in schizophrenia.

A great number of studies have demonstrated the structural and functional abnormalities in chronic schizophrenia (SZ) patients. However, few studies analyzed the differences between first-episode, drug-naive SZ (FESZ) patients and normal controls (NCs). In this study, we recruited 44 FESZ patients and 56 NCs, and acquired their multi-modal magnetic resonance imaging (MRI) data, including structural and resting-state functional MRI data. We calculated gray matter volume (GMV), regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF), and degree centrality (DC) of 90 brain regions, basing on an automated anatomical labeling (AAL) atlas. We then applied these features into support vector machine (SVM) combined with recursive feature elimination (RFE) to discriminate FESZ patients from NCs. Our results showed that the classifier using the combination of ReHo and ALFF as input features achieved the best performance (an accuracy of 96.97%). Moreover, the most discriminative features for classification were predominantly located in the frontal lobe. Our findings may provide potential information for understanding the neuropathological mechanism of SZ and facilitate the development of biomarkers for computer-aided diagnosis of SZ patients.慢性精神分裂症患者大脑的结构和功能异常已经被广泛报道，但是首发未用药精神分裂症患者和正常人的相关研究较少。本研究采集了 44 名首发未用药精神分裂症患者和 56 名正常人的结构和静息态功能磁共振图像，基于自动解剖标签模板提取了 90 个感兴趣区域的灰质体积、局部一致性、低频振荡振幅和度中心度作为特征，并将这些特征作为输入，用基于递归特征消除的支持向量机对首发未用药精神分裂症患者和正常人进行分类。结果表明，局部一致性和低频振荡振幅的组合为最佳分类特征，分类准确率达到 96.97%，并且分类权重最大的脑区主要位于额叶。研究结果有利于加深对精神分裂症神经病理机制的了解，有助于开发出用于临床辅助诊断的生物学标记物。.

This paper is aimed to analyze the topological properties of structural brain networks in depressive patients with and without anxiety and to explore the neuropath logical mechanisms of depression comorbid with anxiety.Diffusion tensor imaging and deterministic tractography were applied to map the white matter structural networks.We collected 20 depressive patients with anxiety(DPA),18 depressive patients without anxiety(DP),and 28 normal controls(NC)as comparative groups.The global and nodal properties of the structural brain networks in the three groups were analyzed with graph theoretical methods.The result showed that1 the structural brain networks in three groups showed small-world properties and highly connected global hubs predominately from association cortices;2DP group showed lower local efficiency and global efficiency compared to NC group,whereas DPA group showed higher local efficiency and global efficiency compared to NC group;3significant differences of network properties(clustering coefficient,characteristic path lengths,local efficiency,global efficiency)were found between DPA and DP groups;4DP group showed significant changes of nodal efficiency in the brain areas primarily in the temporal lobe and bilateral frontal gyrus,compared to DPA and NC groups.The analysis indicated that the DP and DPA groups showed nodal properties of the structural brain networks,compared to NC group.Moreover,the two diseased groups indicated an opposite trend in the network properties.The results of this study may provide a new imaging index for clinical diagnosis for depression comorbid with anxiety.

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p

Background: Suicide is a tremendous public health crisis around the world and is demanded urgent intervention. Most people who die by suicide suffer from some forms of mental illness, especially mood disorders. Previous studies found that Ketamine intervention could rapidly reduce suicidal ideation. The current study is aim to assess the anti-suicidal efficacy of repeated ketamine infusions for Chinese depressed suicidal patients. Methods: In the current study, 112 unipolar and bipolar depressive patients with current suicidal ideation received six ketamine infusions during a 12-day period. Hamilton Depression Rating Scale (HAMD) was measured at baseline, 4 hours and 24 hours after each infusion, two-week naturalistically follow-up. Findings: 59 (53.6%) relief of suicidal ideation (HAMD-SI=0) after first infusion and 71 (73.2%) after six infusions. Anti-suicidal response rate in low SI group were higher than high SI group (F1,1401=56.81, p

Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed.155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS).Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r=-0.210, p0.01) and negative subscore (r=-0.300, p0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18.Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

It has been difficult to identify relevant correlates of inpatient psychiatric length of stay (LOS), but few have examined family burden as a potential factor. The present study investigated the association of several dimensions of family burden with LOS net of other factors. Dimensions of burden experienced by primary caregivers were evaluated in a sample of 602 psychiatric inpatients in a large hospital in Guangzhou, China within 1 week of admission. Factor analysis reduced the burden data to five factors. Bivariate association and multiple linear regression analyzes were used to investigate burden and other factors associated with LOS (average LOS=58.8 days, SD=44.3). Multiple regression analysis showed that in addition to having health insurance coverage, being diagnosed with schizophrenia, being unmarried, and not being employed; being perceived by family members as showing more violent behavior and causing higher levels of caregiver distress were independently associated with longer LOS.

Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas.