Search

Abstract Background Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study.

BackgroundMajor depressive disorder (MDD) is associated with deficits in cognitive function, thought to be related to underlying decreased hedonic experiences. Further research is needed to fully elucidate the role of functional brain activity in this relationship. In this study, we investigated the neurofunctional correlate of the interplay between cognitive function and hedonic experiences in medication-free MDD using functional near-infrared spectroscopy (fNIRS).MethodsWe examine differences of brain activation corresponding to the verbal fluency test (VFT) between MDD patients and healthy controls (HCs). Fifty-six MDD patients and 35 HCs underwent fMRI scanning while performing the VFT. In exploratory analyses, cognitive performance, as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), four dimensions of hedonic processing (desire, motivation, effort, and consummatory pleasure) measured by the Dimensional Anhedonia Rating Scale (DARS), and relative changes in oxygenated hemoglobin concentration during the VFT were compared across groups.ResultsPatients with MDD demonstrated impairments in sustained attention and working memory, accompanied by lower total and subscale scores on the DARS. Compared to healthy controls, MDD patients exhibited reduced activation in the prefrontal cortex (PFC) during the VFT task (t = 2.32 to 4.77, p < 0.001 to 0.02, FDR corrected). DARS motivation, desire, and total scores as well as sustained attention, were positively correlated with activation in the dorsolateral PFC and Broca’s area (p < 0.05, FDR corrected).ConclusionsThese findings indicate that changes in prefrontal lobe oxygenated hemoglobin levels, a region implicated in hedonic motivation and cognitive function, may serve as potential biomarkers for interventions targeting individuals with MDD. Our results corroborate the clinical consensus that the prefrontal cortex is a primary target for non-invasive neuromodulatory treatments for depression.

Background Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p

Abstract Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms. We also explored the relationship between complement factors with CT, cognition and psychotic symptoms. Patients showed significantly higher levels of C1q, C4, factor B, factor H, and properdin in plasma. Among patients, higher levels of C3 in plasma were associated with worse memory recall, while higher levels of C4, factor B and factor H were associated with thinner sensory cortex. These findings link dysregulation of specific complement components to abnormal brain structure and cognition in schizophrenia.

BackgroundThere is an urgent need to identify differentiating and disease-monitoring biomarkers of schizophrenia, bipolar disorders (BD), and major depressive disorders (MDD) to improve treatment and management.MethodsWe recruited 54 first-episode schizophrenia (FES) patients, 52 BD patients, 35 MDD patients, and 54 healthy controls from inpatient and outpatient clinics. α-Melanocyte Stimulating Hormone (α-MSH), β-endorphin, neurotensin, orexin-A, oxytocin, and substance P were investigated using quantitative multiplex assay method. Psychotic symptoms were measured using the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS), manic symptoms using the Young Mania Rating Scale (YMRS), and depressive symptoms using 17 item-Hamilton Depression Rating Scale (HAMD). We additionally measured cognitive function by using a battery of tests given to all participants.Resultsα-MSH, neurotensin, orexin-A, oxytocin, and substance P were decreased in the three patient groups compared with controls. Neurotensin outperformed all biomarkers in differentiating patient groups from controls. There were no significant differences for 6 neuropeptides in their ability to differentiate between the three patient groups. Higher neurotensin was associated with better executive function across the entire sample. Lower oxytocin and higher substance p were associated with more psychotic symptoms in FES and BD groups. β-endorphin was associated with early morning wakening symptom in all three patient groups.ConclusionOur research shows decreased circulating neuropeptides have the potential to differentiate severe mental illnesses from controls. These neuropeptides are promising treatment targets for improving clinical symptoms and cognitive function in FES, BD, and MDD.

Abstract Background Identifying the causal genes at the risk loci and elucidating their roles in schizophrenia (SCZ) pathogenesis remain significant challenges. To explore risk variants associated with gene expression in the human brain and to identify genes whose expression change may contribute to the susceptibility of SCZ, here we report a comprehensive integrative study on SCZ. Methods We systematically integrated the genetic associations from a large-scale SCZ GWAS (N = 56,418) and brain expression quantitative trait loci (eQTL) data (N = 175) using a Bayesian statistical framework (Sherlock) and Summary data-based Mendelian Randomization (SMR). We also measured brain structure of 86 first-episode antipsychotic-naive schizophrenia patients and 152 healthy controls with the structural MRI. Results Both Sherlock (P = 3. 38 × 10−6) and SMR (P = 1. 90 × 10−8) analyses showed that TYW5 mRNA expression was significantly associated with risk of SCZ. Brain-based studies also identified a significant association between TYW5 protein abundance and SCZ. The single-nucleotide polymorphism rs203772 showed significant association with SCZ and the risk allele is associated with higher transcriptional level of TYW5 in the prefrontal cortex. We further found that TYW5 was significantly upregulated in the brain tissues of SCZ cases compared with controls. In addition, TYW5 expression was also significantly higher in neurons induced from pluripotent stem cells of schizophrenia cases compared with controls. Finally, combining analysis of genotyping and MRI data showed that rs203772 was significantly associated with gray matter volume of the right middle frontal gyrus and left precuneus. Conclusions We confirmed that TYW5 is a risk gene for SCZ. Our results provide useful information toward a better understanding of the genetic mechanism of TYW5 in risk of SCZ.

Livestock intensification improves production efficiency and enhances the demand for quality forage to feed ruminants. Novel combinations of forage plants, especially including Gramineae and Leguminous plants, benefit both ruminant animals and contribute to a sustainable environment. This study explored an oat-pea mixed seeding strategy as an approach to improving silage quality. Before ensialing, lactic acid bacteria (Lactobacillus plantarum and Lactobacillus brucelli) were added to forage from five different mixed seeding proportions of oats (O) and peas (P) (10:0, 8:2, 7:3, 5:5, and 0:10 oat to pea ratio) at two harvesting periods (the early flowering stage and the milk ripening stage for the oats). The results showed that mixed seeding changed the soil quality parameters. Moreover, the silage from the O5P5 (5:5 oat to pea ratio) group showed the lowest pH values (4.16) and highest LA contents (7.74% DM) after ensiling for 7d (p < 0.05) in early flowering stage. Also, the O5P5 group increased the number of tillers/branches and produced silage with the highest CP content (13.14–14.06) after ensiling for 7d in early flowering stage and both 7d and 30d in early flowering stage and milk ripening stage (p < 0.05). In conclusion, this study found that the selection of oat-pea mixed seeding as O5P5 and harvesting at the milk ripening stage of oat is recommended as a desirable oat-pea mixed seeding strategy for producing high quality silage.

Although many studies have characterized genetic variation in human populations, few have investigated structural variation and few have been in non-European populations. Here, the authors have performed long read sequencing on 405 Chinese individuals to identify structural variants and link them to phenotypes.

Abstract Background It is unclear whether psychotic experiences (PEs) gradually merge into states of clinical psychosis along a continuum which correspond to a dimensional classification or whether latent classes appear above a certain severity threshold which correspond better to diagnostic categories of psychosis. Methods Annual cross-sectional surveys, 2014–19, among Chinese undergraduates (N = 47,004) measured PEs, depression and etiological risk factors using standardized self-report instruments. We created a psychosis continuum with five levels and tested linear and extra-linear contrasts in associated etiological risk factors, before and after adjustment for depression. We carried out latent class analysis. Results Categorical expression of psychosis, including hallucinations and delusions, nuclear symptoms, and nuclear symptoms and depression were found at severe level 5. Etiological risk factors which impacted linearly across the continuum were more common for depression. Child maltreatment impacted extra-linearly on both psychosis and depression. Family history of psychosis impacted linearly on psychosis; male sex and urban birth impacted extra-linearly and were specific for psychosis. Four latent classes were found, but only at level 5. These corresponded to nuclear schizophrenia symptoms, nuclear schizophrenia and depressive symptoms, severe depression, and an unclassified category with moderate prevalence of PEs. Conclusion Quantitative and qualitative changes in the underlying structure of psychosis were observed at the most severe level along a psychosis continuum, where four latent classes emerged. These corresponded to existing categorical classifications but require confirmation with clinical interview. PEs are non-specific and our findings suggest some are on a continuum with depression, whilst others are on a continuum with non-affective psychosis. Differing patterns of impact from etiological risk factors across the spectrum of psychopathology determine outcome at the most severe level of these continua.

Abstract Background Urban birth and upbringing show consistent associations with psychotic illness but the key urban exposures remain unknown. Associations with psychotic-like experiences (PEs) are inconsistent. These could be confounded by common mental disorders associated with PEs. Furthermore, associations between PEs and urban exposures may not extrapolate to psychotic disorders such as schizophrenia. Methods Annual cross-sectional surveys among first year Chinese undergraduates 2014–2019 (n = 47,004). Self-reported, hierarchical categorisation of psychosis: from psychoticism, paranoid ideation, schizotypal symptoms, nuclear syndrome using SCL-90-R, to clinical diagnosis of schizophrenia. Depressive symptoms using PHQ 9. Dissociative symptoms and posttraumatic stress disorder (PTSD) measured using PCL-C. Etiological factors of family history and childhood disadvantage. We studied effects of urban birth, urban living and critical times of exposure in childhood on psychosis phenotypes. Results Associations with urbanicity were found only after adjustments for depression. Urban birth was associated with paranoia (AOR 1.34, 1.18–1.53), schizotypal symptoms (AOR 1.59, 1.29–1.96), and schizophrenia (AOR 2.07, 1.10–3.87). The same phenotypes showed associations with urban residence > 10 years. Only schizophrenia showed an association with urban exposure birth-3 years (AOR 7.01, 1.90–25.86). Child maltreatment was associated with both psychosis and depression. Urbanicity measured across the total sample did not show any associations with demography, family history of psychosis, or child maltreatment. Sensitivity analysis additionally adjusting for dissociative symptoms and PTSD showed the same pattern of findings. Conclusions Urban birth and urban living showed a hierarchical pattern of increasing associations from paranoid ideation to schizotypal disorder to schizophrenia, confirming that associations for psychotic experiences could be extrapolated to schizophrenia, but only after adjusting for confounding from depression, dissociative symptoms and PTSD. Several etiological factors were the same for psychosis and depression. Future studies of PEs should adjust for confounding from common mental disorders and dissociative symptoms. Effects of urbanicity on psychosis were not explained by demography, family history of mental disorder, or child maltreatment.

Emerging evidence has demonstrated overlapping biological abnormalities underlying schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD); these overlapping abnormalities help explain the high heterogeneity and the similarity of patients within and among diagnostic categories. This study aimed to identify transdiagnostic subtypes of these psychiatric disorders based on lipidomics abnormalities. We performed discriminant analysis to identify lipids that classified patients (N = 349, 112 with SCZ, 132 with BP, and 105 with MDD) and healthy controls (N = 198). Ten lipids that mainly regulate energy metabolism, inflammation, oxidative stress, and fatty acylation of proteins were identified. We found two subtypes (named Cluster 1 and Cluster 2 subtypes) across patients with SCZ, BP, and MDD by consensus clustering analysis based on the above 10 lipids. The distribution of clinical diagnosis, functional impairment measured by Global Assessment of Functioning (GAF) scales, and brain white matter abnormalities measured by fractional anisotropy (FA) and radial diffusivity (RD) differed in the two subtypes. Patients within the Cluster 2 subtype were mainly SCZ and BP patients and featured significantly elevated RD along the genu of corpus callosum (GCC) region and lower GAF scores than patients within the Cluster 1 subtype. The SCZ and BP patients within the Cluster 2 subtype shared similar biological patterns; that is, these patients had comparable brain white matter abnormalities and functional impairment, which is consistent with previous studies. Our findings indicate that peripheral lipid abnormalities might help identify homogeneous transdiagnostic subtypes across psychiatric disorders.

Schizophrenia (SCZ) and bipolar disorder (BD) are debilitating neurodevelopmental disorders with high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by three females. An adolescent female was clinically diagnosed as first-episode SCZ. One of her cousins was clinically diagnosed as BD and another one was unaffected control. Induced pluripotent stem cells (iPSCs) were established with reprograming factors Oct4, Sox2, Nanog, Lin28, c-myc, Klf4, and SV40LT. All lines presented normal karyotype and highly expressed pluripotency markers in vitro. All iPSCs were capable to differentiate into derivatives of three germ layers in vivo.

With less exposure to environmental and medication influences, individuals with early-onset schizophrenia (EOS) may provide valuable evidence to study the pathogenesis and phenotypic pattern of schizophrenia.T1-weighted magnetic resonance images were collected in 60 individuals with EOS and 40 healthy controls. Voxel-based morphometry and surface-based morphometry analyzes were performed. Gray matter volume, cortical thickness and cortical surface area were compared between the EOS and healthy controls and among schizophrenia subgroups (with or without family history of schizophrenia). Compared with healthy controls, the EOS group had reduced gray matter volume in the bilateral middle temporal gyrus and reduced cortical thickness in several brain regions. The sporadic early onset schizophrenia and the familial early onset schizophrenia showed different brain structure morphology. These findings suggest that abnormal brain structure morphology, especially in the temporal and frontal lobes, may be an important pathophysiological feature of EOS.

Abstract Background Residential mobility during childhood increases risk of psychopathology in adulthood and is a common experience among Chinese children. This study investigated associations between number and age of first move, etiological risk factors for psychopathology, and common mental disorders in adolescence and early adulthood. Methods The sample included 39,531 undergraduates (84.5% completion rate) age 15–34 years in their first year at a Chinese comprehensive university in annual cross-sectional surveys during 2014–2018. Common mental disorders measured using standardised self-report instruments. Data analysed using logistic regression models and interaction analysis. Results Half of all students experienced one or more moves of residence before age 15 years. Outcomes of Depression, Somatisation, Obsessive-compulsive disorder, Hallucinations and Delusions, and Suicide attempts showed dose-response relationships with increasing number of moves. Other etiological risk factors, including childhood disadvantage and maltreatment, showed similar dose response relationships but did not confound associations with mobility. We found interactions between reporting any move and being a left-behind child on depression and somatisation; number of moves and younger age at first move on depression, somatisation, suicide attempts and hallucinations and delusions. Conclusions Residential mobility in childhood is associated with psychopathology in adulthood and this association increases with increasing number of moves. Mobility is also associated with childhood disadvantage and maltreatment but associations with psychopathology are independent of these factors. Multiplicative effects were shown for multiple moves starting at a younger age and if the participant had been a left-behind child.

IntroductionPrevious studies on transcriptional profiles suggested dysregulation of multiple RNA species in major depressive disorder (MDD). However, the interaction between different types of RNA was neglected. Therefore, integration of different RNA species in transcriptome analysis would be helpful for interpreting the functional readout of the transcriptome in MDD.MethodsA whole transcriptome sequencing were performed on the peripheral blood of 15 patients with MDD and 15 matched healthy controls (HCs). The differential expression of miRNAs, lncRNAs, circRNAs, and mRNAs was examined between MDD and HCs using empirical analysis of digital gene expression data in R (edgeR). Weighted correlation network analysis (WGCNA) was used to identify RNA co-expression modules associated with MDD. A ceRNA network was constructed for interpretation of interactions between different RNA species. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to explore potential biological mechanisms associated with MDD.ResultsMultiple RNAs and co-expression modules were identified to be significantly dysregulated in MDD compared to HCs. Based on the differential RNAs, a ceRNA network that were dysregulated in MDD were constructed. The pathway networks that related to oxidative phosphorylation and the chemokine signaling were found to be associated with MDD.ConclusionOur results suggested that the processes of energy metabolism and inflammation may be involved in the pathophysiology of MDD.

Schizophrenia (SCZ) is a debilitating neurodevelopmental disorder with a high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by a pair of dizygotic twins. The female was clinically diagnosed as SCZ by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria, and her unaffected male sibling was healthy control. Induced pluripotent stem cells (iPSCs) were established using Episomal vectors carrying reprograming factors OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT. These lines with normal karyotype highly expressed pluripotency markers and are capable to differentiate into derivatives of three germ layers. Both lines are negative of mycoplasma.

PurposeUniversity students experience high levels of stress, and the prevalence of depression is higher than in the general population. The reason is not clear. More effective interventions and better prevention are needed.MethodsWe did annual cross-sectional surveys of Chinese undergraduates 2014–2018 (mean age 18.7 [SD 2.1], N = 39,573). We measured adaptation to university life using the Adolescent Self-rating Life Events Checklist (ASLEC) and common mental disorders using standardized self-report instruments. Regression analyses identified associations between childhood maltreatment, current family problems, stress in adaptation to undergraduate life, and psychiatric morbidity. Mediation analyses further tested relationships between these factors.ResultsChildhood maltreatment, current family problems, stress in adaptation, and psychiatric morbidity were all significantly associated with each other. The strongest association between childhood experiences and psychiatric morbidity was for sexual abuse and depression (OR = 3.39, 95%CI: 2.38–4.83, p < 0.001) and between stress from adaptation and somatic disorder (OR = 4.54, 95%CI: 3.62–5.68, p < 0.001). Associations between childhood maltreatment and stress from university life were partly mediated by psychiatric morbidity. Associations between family problems and psychiatric morbidity were mediated by stress from university life.ConclusionsStress from adaptation to university life and pressures from academic study exert stronger effects on psychiatric morbidity among students than childhood traumatic experiences and current family problems, although these factors are closely interrelated. Mental health services for students should focus on adaptation to university life and pressures from academic study as well as external factors of childhood trauma and family problems.

Nodular cast iron QT700-2 is extensively used in automobile engine crankshaft parts due to its prime mechanical properties. The journal of a crankshaft is a curved surface, and traditional wheel grinding easily causes grinding burn and surface and subsurface damage. Shape adaptive grinding (SAG) is a flexible grinding technology, which has the advantages of low grinding force and temperature, and good grinding quality. It is suitable for machining curved surface parts with complex shapes. Therefore, the SAG surface integrity of nodular cast iron QT700-2 was experimentally investigated. The influence of grinding parameters on grinding force, material removal rate, grinding temperature, and surface integrity was studied, and the machining performance of SAG tools was evaluated. It was concluded that the grain size in SAG is the most important factor affecting the grinding force, material removal rate, and surface roughness; the influence of SAG grinding is very weak, mainly removing the workpiece material. Then, the influence law of SAG technology on the surface integrity of nodular cast iron QT700-2 was summarized, and the optimal grinding parameters were obtained, providing a reference for the curved surface grinding of nodular cast iron QT700-2 in the future.

Background: Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated.Methods: To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms.Results: Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms.Conclusions: Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Background Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model. Aims We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia. Method This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months. Results This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients. Conclusion This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.

Background Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design. Aims This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934). Method Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups. Results The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine. Conclusions The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.

Objective Major depressive disorder is associated with abnormal functioning of the hypothalamic–pituitary–adrenal (HPA) axis. Studies using hair cortisol to measure the effect of antidepressants on the HPA axis are lacking. The aim of this study was to explore the long-term effects of antidepressants on hair cortisol concentration (HCC). Methods Participants were 42 patients and 36 healthy individuals. The patients took antidepressants for 4 weeks. Patient HCC was measured pre-treatment and post-treatment. The HCC of healthy controls was also measured. Results Patient post-treatment HCC (mean ± standard deviation: 34.40 ± 32.57 pmol/mg) was significantly higher than patient pre-treatment HCC (17.42 ± 12.40 pmol/mg) and healthy control HCC (10.22 ± 7.99 pmol/mg). No significant correlation was found between Hamilton Depression Rating Scale scores and HCC at pre-treatment or post-treatment. Conclusions Hair cortisol concentration analysis could be used to monitor the dynamics of the effects of antidepressants on the HPA axis.

Animal feed (including forage and silage) can be contaminated with mycotoxins. Here, 200 maize silage samples from around China were collected in 2019 and analyzed for regulated mycotoxins, masked mycotoxins (deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and deoxynivalenol-3-glucoside), and emerging mycotoxins (beauvericin, enniatins, moniliformin, and alternariol). Deoxynivalenol and zearalenone were detected in 99.5% and 79.5% of the samples, respectively. Other regulated mycotoxins were detected in fewer samples. The highest deoxynivalenol and zearalenone concentrations were 3600 and 830 μg/kg, respectively. The most commonly detected masked mycotoxin was 15-acetyldeoxynivalenol, which was detected in 68.5% of the samples and had median and maximum concentrations of 61.3 and 410 μg/kg, respectively. The emerging mycotoxins beauvericin, alternariol, enniatin A, enniatin B1, and moniliformin were detected in 99.5%, 85%, 80.5%, 72.5%, and 44.5%, respectively, of the samples but at low concentrations (medians

The objective of this study was to investigate the effect of a diet supplemented with fresh amla fruit as a natural feed additive on blood metabolic parameters, milk antioxidant capacity, and milk fatty acid (FA) proportions in lactating dairy cows. Eight ruminally cannulated mid-lactation dairy cows were used in a repeated crossover design. The first group of four cows received total mixed ration (TMR) feed without fresh amla fruit (control group). The remaining four cows sequentially supplemented fresh amla fruit (FAF) at three levels (200, 400, then 600 g/d) (treatment group) at 14-day intervals. In second period, control and treatment groups were exchanged. The first ten days were adjusted to diet adaptation for each sub-period, and the last four days for sampling milk and blood. A total of 514 metabolites were detected from FAF using UPLC-ESI-MS/MS. The five main metabolites in FAF were phenolic acids (22%), flavonoids (20%), lipids (20%), amino acids and derivatives (9%), and tannins (7%). Amla fruit supplementation reduced total saturated fatty acid and the omega-6/omega-3 ratio at 200 or 400 g/d FAF dose compared to controls. In addition, amla fruit increased unsaturated FA, such as C20:5 (Eicosapentaenoic acid, EPA) and C22:6 (docosahexaenoic acid, DHA), and branched-chain FA in a dose-dependent manner at 200 or 400 g/d compared to controls. In addition, amla fruit increased the antioxidant capacity biomarkers in the blood, such as superoxide dismutase (SOD) and albumin; this confirms that amla fruit is an excellent antioxidant, inhibiting reactive oxygen species’ (ROS) metabolism, and can thereby protect cells from oxidative stress. Moreover, the most remarkable improvement of ferric reducing-antioxidant power (FRAP) and total antioxidant capacity (TAC) in milk was recorded at 400 g/d FAF doses compared to controls. Therefore, fresh amla fruit doses for lactating cows at 400 g/d on an as-fed basis can be used as an alternative additive feed in dairy cow diets to improve antioxidant capacity, protein efficiency, butter quality, and to produce more desirable milk fatty acid profiles for human consumption.

Abstract The current study aimed to explore age-variant trait differences of cortical gray matter volume (GMV) in a unique sample of first-episode and treatment-naïve patients with schizophrenia. A total of 158 subjects, including 26 adolescent-onset patients and 49 adult-onset patients as well as 83 age- and gender-matched controls were scanned using a 3T MRI scanner. Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL) was used to explore group differences between patients and controls in regional GMV. We found that patients with schizophrenia had decreased GMV in the left parietal postcentral region that extended to the left frontal regions, the right middle temporal gyrus, the occipital lobe and the right cerebellum posterior pyramis. Further analysis showed a distinct pattern of gray matter alterations in adolescent-onset patients compared with both healthy controls and adult-onset patients. Relative to healthy controls, adolescent-onset patients showed GMV alterations in the left parietal postcentral gyrus, parahippocampal gyrus and right cerebellum posterior pyramis, while GMV deficits in adult-onset patients were focused on the cingulo-fronto-temporal module and right occipital regions. Our study identified differential cortical gray matter deficits between adolescent- and adulthood-onset patients with schizophrenia, which suggests that the cortical abnormalities in schizophrenia are likely adjusted by the developmental community structure of the human brain.

Abstract This study was to explore the sex differences in clinical characteristics and brain gray matter volume (GMV) alterations in 29 male patients with major depressive disorder (MDDm), 53 female patients with MDD (MDDf), and in 29 male and 53 female matched healthy controls. Maps of GMV were constructed using magnetic resonance imaging data and compared between groups. We evaluated clinical symptoms using the Hamilton Rating Scale for Depression and obtained a total score and five syndrome scores. A two-factor ANCOVA model was specified using SPM8, with sex and diagnosis as the between-subject factors. We found that: (1) significant GMV increase in the left cerebellum and GMV reduction in the bilateral middle temporal gyrus and left ventral medial prefrontal gyrus occurred selectively in male patients, while the GMV reduction in the left lingual gyrus and dorsal medial prefrontal gyrus occurred selectively in female patients; (2) MDDf may have experienced more severe sleep disturbance than MDDm; and (3) the severity of sleep symptom could be predicted by the sex specific brain structural alterations in depressions. These findings suggest that sex specific anatomical alterations existed in MDD, and these alterations were associated with the clinical symptoms.

Background: Promising biomarkers would be used to improve the determination of diagnosis and severity, as well as the prediction of symptomatic and functional outcomes of schizophrenia. Basic procedures: In this study, we used three different mouse models induced by a genetic factor (PV-Cre; ErbB4−/−, G group), an environmental stressor (adolescent social isolation, G group), and a combination of genetic factor and environmental stressor (PV-Cre; ErbB4−/− mice with isolation, G × E group). Attenuated PPI (%) confirmed the successful establishment of three schizophrenia-like mouse models. To evaluate whether neuropeptide levels in plasma would be potential biomarkers of different schizophrenia models in our work, we used MILLIPLEX® MAP method to simultaneously measure 6 critical neuropeptides in plasma. Main findings: Among the evaluated neuropeptides, increased neurotensin tends to be associated with genetic factors of schizophrenia, increased orexin A seems to be a biomarker of an interplay between genetic and social isolation, while higher plasma oxytocin might be more apt to be responsive to social isolation. The potential biomarkers are mostly independent of sex. Conclusions: This research would provide novel clues to develop circulating biomarkers of plasma neuropeptides for multifactorial schizophrenia. Keywords: Schizophrenia, Neuropeptides, Biomarkers, Genetic factor, Social isolation, Dual-hit model

Background: Voxel-based morphometry studies have repeatedly highlighted the presence of distributed gray matter changes in schizophrenia, but to date, it is not clear if clinically useful prognostic information can be gleaned from structural imaging. The suspected association between gray matter volume (GMV) and duration of psychotic illness, antipsychotic exposure, and symptom severity also limits the prognostic utility of morphometry. We address the question of whether morphometric information from patients with drug-naive first-episode psychosis can predict the linear trajectory of symptoms following early antipsychotic intervention using a longitudinal design.Method: Sixty-two first-episode, drug-naive patients with schizophrenia underwent brain magnetic resonance imaging scans at baseline, treated with antipsychotics, and rescanned after 1-year follow-up. Positive and Negative Syndrome Scale (PANSS) was used to assess their clinical manifestations. A multivariate approach to detect covariance-based network-like spatial components [Source Based Morphometry (SBM)] was performed to analyze the GMV. Paired t tests were used to study changes in the loading coefficients of GMV in the spatial components between two time points. The reduction in PANSS scores between the baseline (T0) and 1-year follow-up (T1) expressed as a ratio of the baseline scores (reduction ratio) was computed for positive, negative, and disorganization symptoms. Separate multiple regression analyses were conducted to predict the longitudinal change in symptoms (treatment response) using the loading coefficients of spatial components that differed between T0 and T1 with age, gender, duration of illness, and antipsychotic dose as covariates. We also tested the putative “toxicity” effects of baseline symptom severity on the GMV at 1 year using multiple regression analysis.Results: Of the 30 spatial components of gray matter extracted using SBM, loading coefficients of anterior cingulate cortex (ACC), insula and inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG), precuenus, and dorsolateral prefrontal cortex (DLPFC) reduced with time in patients. Specifically, the lower volume of insula and IFG at baseline predicted a lack of improvement in positive and disorganization symptoms. None of the symptom severity scores (positive, negative, or disorganization) at baseline independently predicted the reduced GMV at 1 year.Conclusions: The baseline deficit in a covariance-based network-like spatial component comprising of insula and IFG is predictive of the clinical course of schizophrenia. We do not find any evidence to support the notion of symptoms per se being neurotoxic to gray matter tissue. If judiciously combined with other available predictors of clinical outcome, multivariate morphometric information can improve our ability to predict prognosis in schizophrenia.

The objective of this study was to estimate cow variability that can be used to determine the optimal sample size for digestibility trials using lactating dairy cows. Experimental design was randomized complete block design having three blocks and three dietary treatments. Three similarly managed nearby intensive farms were considered as blocks, and three diets were formulated to have 0.7, 1.0, and 1.3 neutral detergent fiber (NDF): starch ratio. In each farm, 18 cows were assigned for each dietary treatment and five sample sizes per each treatment group were simulated by simple random sampling of data from 18, 15, 12, 9 and 6 cows respectively. Intake was not affected by diet or sample size (p > 0.05). Estimated cow variability (as standard deviation) for digestibility of dry matter, NDF and starch were 3.8 g/kg, 5.1 g/kg and 3.3 g/kg, respectively. A major implication of this study is that cow variability is greatest for NDF digestibility and the use of a minimum of 12 cows per dietary treatment is adequate to reliably detect treatment effects on the digestibility of NDF, starch and dry matter using cows fed in groups with randomized block design under these experimental conditions.

Background: It is unclear whether psychotic experiences (PEs) gradually merge into states of clinical psychosis along a continuum which correspond to a dimensional classification or whether latent classes appear above a certain severity threshold which correspond better to diagnostic categories of psychosis. Methods: Annual cross-sectional surveys, 2014-19, among Chinese undergraduates (N = 47,004) measured PEs, depression and etiological risk factors using standardized self-report instruments. We created a psychosis continuum with five levels and tested linear and extra-linear contrasts in associated etiological risk factors, before and after adjustment for depression. We carried out latent class analysis. Results: Categorical expression of psychosis, including hallucinations and delusions, nuclear symptoms, and nuclear symptoms and depression were found at severe level 5. Etiological risk factors which impacted linearly across the continuum were more common for depression. Child maltreatment impacted extra-linearly on both psychosis and depression. Family history of psychosis impacted linearly on psychosis; male sex and urban birth impacted extralinearly and were specific for psychosis. Four latent classes were found, but only at level 5. These corresponded to nuclear schizophrenia symptoms, nuclear schizophrenia and depressive symptoms, severe depression, and an unclassified category with moderate prevalence of PEs. Conclusion: Quantitative and qualitative changes in the underlying structure of psychosis were observed at the most severe level along a psychosis continuum, where four latent classes emerged. These corresponded to existing categorical classifications but require confirmation with clinical interview. PEs are non-specific and our findings suggest some are on a continuum with depression, whilst others are on a continuum with non-affective psychosis. Differing patterns of impact from etiological risk factors across the spectrum of psychopathology determine outcome at the most severe level of these continua. [ABSTRACT FROM AUTHOR]

There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuations, grey matter volume, and fractional anisotropy. The multimodal components correlated with miR-132 also show significant group difference in loadings. Results indicate that (i) higher miR-132 levels in major depressive disorder are associated with both lower fractional amplitude of low frequency fluctuations and lower grey matter volume in fronto-limbic network; and (ii) the identified brain regions linked with increased miR-132 levels were also associated with poorer cognitive performance in attention and executive function. Using a data-driven, supervised-learning method, we determined that miR-132 dysregulation in major depressive disorder is associated with multi-facets of brain function and structure in fronto-limbic network (the key network for emotional regulation and memory), which deepens our understanding of how miR-132 dysregulation in major depressive disorders contribute to the loss of specific brain areas and is linked to relevant cognitive impairments. [ABSTRACT FROM AUTHOR]

Background: Impaired visual memory seems to be a core feature of depression, while increased microRNA-132 (miR-132) levels have been widely reported in depression patients. The authors aimed to explore the relationship between miR-132 changes and visual memory deficits in unmedicated patients with major depressive disorder (MDD). Patients and methods: A total of 62 medication-free MDD patients and 73 matched healthy controls (HCs) were tested for miR-132 expression level in peripheral blood using quantitative realtime polymerase chain reaction. We used a computerized neurocognitive task from the Cambridge Neuropsychological Test Automated Battery (CANTAB) - pattern recognition memory (PRM) task - as a measurement of visual memory. The relationship between visual memory, miR-132 expression level, and clinical symptoms was explored in patients with MDD. Results: Upregulated miR-132 expression levels were seen in MDD patients but not in HCs. Two-sample t-tests showed that MDD patients had decreased visual memory, mainly memory delayed compared to that of HCs. Correlation analyses revealed that in MDD patients, increased miR-132 expression levels were significantly correlated with visual memory as measured by the CANTABPRM. Hamilton Rating Scale for Anxiety scores were negatively correlated with PRM - number correct (immediate) and PRM - percent correct (immediate). Limitations: The main limitations were missing data and lack of follow-up studies. Conclusion: Our study suggests that increased miR-132 expression levels were associated with visual memory deficits, which may underlie the pathophysiology of MDD. In individuals with depression, immediate visual memory defects were positively correlated with anxiety symptoms. [ABSTRACT FROM AUTHOR]

Background: Impaired sustained attention seems to be a core feature of depression while the anatomical alteration of brain was widely reported in depression patients. The authors aimed to identify the relationship between anatomical brain changes and sustained attention deficits in unmedicated patients with major depressive disorder (MDD). Methods: A total of 51 medication-free MDD patients and 51 matched healthy controls (HC) underwent high-resolution structural magnetic resonance imaging scanning, and optimized voxel-based morphometry method was performed to analyze the changes of gray matter volume (GMV). We employed a computerized neurocognitive task from the Cambridge Neuropsychological Tests Automated Battery (CANTAB) - Rapid Visual Information Processing (RVP) task -- as a measurement of sustained attention. Based on clinical symptoms, 40 patients who had completed CANTAB-RVP test were divided into MDDa (mild depression patients) and MDDb (severe depression patients) groups. Then the relationships among sustained attention, GMV of different regions and clinical symptoms were explored separately. Results: MDD patients showed significant GMV increase in left posterior cingulate cortex (PCC) and inferior frontal gyrus (IFG) (p<0.001, uncorrected), and significant GMV decrease in medial/superior frontal gyrus (MFG/SFG) and lingual gyrus (p<0.001, uncorrected). Structure-cognition correlation analyses revealed that in MDD patients, GMV alterations of the IFG were significantly correlated with sustained attention as measured by the CANTAB-RVP. Conclusions: Increased GMV values of IFG were associated with sustained attention which may underlie the pathophysiology of MDD or be part of the cognition circuit. In the severe depression patients, sustained attention deficits were positively correlated with clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD). Patients and Methods: Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV) and regional homogeneity (ReHo) between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results: Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P,0.001, uncorrected). In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P,0.001, uncorrected) in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion: Our study suggests a dissociation pattern of brain regions with anatomical and functional alterations in unmedicated patients with MDD, especially with regard to GMV and ReHo. [ABSTRACT FROM AUTHOR]