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Major depressive disorder frequently leads to cognitive impairments, significantly affecting patients' quality of life. However, the neurobiological mechanisms underlying cognitive deficits remain unclear. This study aimed to explore multimodal imaging biomarkers associated with cognitive function in major depressive disorder. Five cognitive scores (sustained attention, visual recognition memory, pattern recognition memory, executive function, and working memory) were used as references to guide the fusion of gray matter volume and amplitude of the low frequency fluctuation. Social function was assessed after 2 yr. Linear regression analysis was performed to identify brain features that were associated with social function of patients with major depressive disorder. Finally, we included 131 major depressive disorder and 145 healthy controls. A multimodal frontal-insula-occipital network associated with sustained attention was found to be associated with social functioning in major depressive disorders. Analysis across different cognitive domains revealed that gray matter volume exhibited greater sensitivity to differences, while amplitude of the low frequency fluctuation consistently decreased in the right temporal-occipital-hippocampus circuit. The consistent functional changes across the 5 cognitive domains were related to symptom severity. Overall, these findings provide insights into biomarkers associated with multiple cognitive domains in major depressive disorder. These results may contribute to the development of effective treatment targeting cognitive deficits and social function.
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Encéfalo , Cognição , Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Feminino , Masculino , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Cognição/fisiologia , Pessoa de Meia-Idade , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Testes Neuropsicológicos , Imagem Multimodal , Função Executiva/fisiologia , Atenção/fisiologia , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologiaRESUMO
Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.
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Transtorno Depressivo Maior , Função Executiva , Imageamento por Ressonância Magnética , Imagem Multimodal , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Adolescente , Função Executiva/fisiologia , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Neuroimagem/métodos , Cognição/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Mapeamento Encefálico/métodosRESUMO
BACKGROUND: Over the past several decades, more research focuses have been made on the inflammation/immune hypothesis of schizophrenia. Building upon synaptic plasticity hypothesis, inflammation may contribute the underlying pathophysiology of schizophrenia. Yet, pinpointing the specific inflammatory agents responsible for schizophrenia remains a complex challenge, mainly due to medication and metabolic status. Multiple lines of evidence point to a wide-spread genetic association across genome underlying the phenotypic variations of schizophrenia. METHOD: We collected the latest genome-wide association analysis (GWAS) summary data of schizophrenia, cytokines, and longitudinal change of brain. We utilized the omnigenic model which takes into account all genomic SNPs included in the GWAS of trait, instead of traditional Mendelian randomization (MR) methods. We conducted two round MR to investigate the inflammatory triggers of schizophrenia and the resulting longitudinal changes in the brain. RESULTS: We identified seven inflammation markers linked to schizophrenia onset, which all passed the Bonferroni correction for multiple comparisons (bNGF, GROA(CXCL1), IL-8, M-CSF, MCP-3 (CCL7), TNF-ß, CRP). Moreover, CRP were found to significantly influence the linear rate of brain morphology changes, predominantly in the white matter of the cerebrum and cerebellum. CONCLUSION: With an omnigenic approach, our study sheds light on the immune pathology of schizophrenia. Although these findings need confirmation from future studies employing different methodologies, our work provides substantial evidence that pervasive, low-level neuroinflammation may play a pivotal role in schizophrenia, potentially leading to notable longitudinal changes in brain morphology.
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BACKGROUND: Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES). METHODS: Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored. RESULTS: Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR-p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR-p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR-p = 0.034). CONCLUSION: Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics.
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Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD.
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Microglia , Privação do Sono , Camundongos , Masculino , Animais , Encéfalo , Hipocampo , Tonsila do CerebeloRESUMO
Across the major psychiatric disorders (MPDs), a shared disruption in brain physiology is suspected. Here we investigate the neural variability at rest, a well-established behavior-relevant marker of brain function, and probe its basis in gene expression and neurotransmitter receptor profiles across the MPDs. We recruited 219 healthy controls and 279 patients with schizophrenia, major depressive disorder, or bipolar disorders (manic or depressive state). The standard deviation of blood oxygenation level-dependent signal (SDBOLD) obtained from resting-state fMRI was used to characterize neural variability. Transdiagnostic disruptions in SDBOLD patterns and their relationships with clinical symptoms and cognitive functions were tested by partial least-squares correlation. Moving beyond the clinical sample, spatial correlations between the observed patterns of SDBOLD disruption and postmortem gene expressions, Neurosynth meta-analytic cognitive functions, and neurotransmitter receptor profiles were estimated. Two transdiagnostic patterns of disrupted SDBOLD were discovered. Pattern 1 is exhibited in all diagnostic groups and is most pronounced in schizophrenia, characterized by higher SDBOLD in the language/auditory networks but lower SDBOLD in the default mode/sensorimotor networks. In comparison, pattern 2 is only exhibited in unipolar and bipolar depression, characterized by higher SDBOLD in the default mode/salience networks but lower SDBOLD in the sensorimotor network. The expression of pattern 1 related to the severity of clinical symptoms and cognitive deficits across MPDs. The two disrupted patterns had distinct spatial correlations with gene expressions (e.g., neuronal projections/cellular processes), meta-analytic cognitive functions (e.g., language/memory), and neurotransmitter receptor expression profiles (e.g., D2/serotonin/opioid receptors). In conclusion, neural variability is a potential transdiagnostic biomarker of MPDs with a substantial amount of its spatial distribution explained by gene expressions and neurotransmitter receptor profiles. The pathophysiology of MPDs can be traced through the measures of neural variability at rest, with varying clinical-cognitive profiles arising from differential spatial patterns of aberrant variability.
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OBJECTIVES: Carotid artery stenosis (CAS) is a leading cause of cerebral ischemic events (CIE). Timely detection and risk assessment can aid in managing CAS patients and improving their prognosis. The aim of the current study is to identify a new biomarker for CAS and to further investigate the impact of miR-195-5p on cellular processes in vascular smooth muscle cells (VSMCs). METHODS: This study involved 112 CAS patients and 65 healthy individuals. Serum miR-195-5p levels were measured using RT-qPCR. The ROC curve was then plotted to evaluate the diagnostic potential of miR-195-5p for CAS. The Kaplan-Meier curve and Cox regression were employed to determine miR-195-5p's prognostic significance. In vitro, the effects of miR-195-5p mimic or inhibitor on VSMC proliferation and migration were assessed using CCK-8 and Transwell assays. RESULTS: In CAS patients, serum miR-195-5p levels were elevated and correlated with the degree of CAS. The ROC curve had an AUC value of 0.897, with sensitivity of 71.4% and specificity of 95.4%. Higher levels of miR-195-5p indicated a higher risk of CIE occurrence and may serve as an independent predictor of CIE. The upregulation of miR-195-5p promoted VSMC proliferation and migration, while downregulation had the opposite effect. CONCLUSIONS: miR-195-5p was demonstrated to have diagnostic and prognostic significance in CAS and may serve as a potential biomarker. It may contribute to the progression of CAS by promoting the proliferation and migration of VSMCs.
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BACKGROUND: To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ). METHODS: We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ. RESULTS: TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ. CONCLUSIONS: Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
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BACKGROUND: Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning. METHODS: Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm. RESULTS: Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = -0.31). In BPD, MMN was significantly correlated with DMS (r = -0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD. CONCLUSIONS: The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.
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Transtorno Bipolar , Esquizofrenia , Adulto , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Eletroencefalografia , Potenciais Evocados , Potenciais Evocados P300 , Potenciais Evocados Auditivos , Estimulação AcústicaRESUMO
BACKGROUND: Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders. METHODS: A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components. RESULTS: GMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level. CONCLUSIONS: BD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.
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Transtorno Bipolar , Transtorno Depressivo Maior , Córtex Motor , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Fator H do Complemento , Properdina , Complemento C1q , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologiaRESUMO
BACKGROUND: Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear. METHODS: 343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying 'networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied. RESULTS: Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests. CONCLUSIONS: In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Substância Cinzenta/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Córtex Cerebral , Córtex Pré-Frontal , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure-function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). METHODS: We quantified the dynamic structure-function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure-function coupling with the topological features of functional networks to examine how the structure-function relationship facilitates brain information communication over time. RESULTS: The dynamic structure-function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure-function coupling and the topological features of functional networks are altered in a manner indicative of state specificity. CONCLUSIONS: These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure-function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.
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Aberrations in intracortical myelination are increasingly being considered as a cardinal feature in the pathophysiology of schizophrenia. We investigated the network-level distribution of intracortical myelination across various cortex depths. We enrolled 126 healthy subjects and 106 first-episode drug-naïve schizophrenia patients. We used T1w/T2w ratio as a proxy of intracortical myelination, parcellated cortex into several equivolumetric surfaces based on cortical depths and mapped T1w/T2w ratios to each surface. Non-negative matrix factorization was used to generate depth-dependent structural covariance networks (dSCNs) of intracortical myelination from 2 healthy controls datasets-one from our study and another from 100-unrelated dataset of the Human Connectome Project. For patient versus control comparisons, partial least squares approach was used; we also related myelination to clinical features of schizophrenia. We found that dSCNs were highly reproducible in 2 independent samples. Network-level myelination was reduced in prefrontal and cingulate cortex and increased in perisylvian cortex in schizophrenia. The abnormal network-level myelination had a canonical correlation with symptom burden in schizophrenia. Moreover, myelination of prefrontal cortex correlated with duration of untreated psychosis. In conclusion, we offer a feasible and sensitive framework to study depth-dependent myelination and its relationship with clinical features.
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Conectoma , Transtornos Psicóticos , Esquizofrenia , Encéfalo , Humanos , Imageamento por Ressonância MagnéticaRESUMO
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.
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Oxigenases de Função Mista , Esquizofrenia , Teorema de Bayes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Oxigenases de Função Mista/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genéticaRESUMO
BACKGROUND: Alcohol dependence is a mental disorder with a high relapse rate. However, specific neuroimaging biomarkers have not been determined for alcohol dependence and its relapse. We conducted data-driven research to investigate resting-state functional magnetic resonance imaging (rs-fMRI) during early abstinence from alcohol dependence and its potential ability to predict relapse. METHODS: Participants included 68 alcohol-dependent patients and 68 healthy controls (HCs). The regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were compared between the alcohol dependence group and the HCs and between the relapse group and the nonrelapse group. The brain regions that presented significantly different ReHo and/or fALFF between the alcohol-dependent patients and HCs and/or between the relapsed and nonrelapsed patients were selected as the seeds to calculate the functional connectivities (FCs). RESULTS: During a 6-month follow-up period, 52.24% of alcohol-dependent patients relapsed. A regression model for differentiating alcohol-dependent patients and HCs showed that reductions in ReHo in the left postcentral region, fALFF in the right fusiform region, and FC in the right fusiform region to the right middle cingulum were independently associated with alcohol dependence, with an area under the receiver operating characteristic curve (AUC) of 0.841. The baseline FC of the left precentral to the left cerebellum of the relapse group was significantly lower than that of the nonrelapse group. The AUC of this FC to predict relapse was 0.774. CONCLUSIONS: Our findings contribute to advancing research on the neurobiological etiology and predictive biomarkers for relapse associated with alcohol dependence.
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Alcoolismo , Alcoolismo/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , RecidivaRESUMO
This study evaluated the effects of two organic acids on the fermentation of alfalfa silages at different dry matter (DM) contents. Alfalfa was wilted to DM contents of 30% (moderately low) and 38% (normal) and ensiled without additives (control) or treated with 0.6% fresh matter DL-malic acid (MA) or 0.6% fresh matter citric acid (CA) for 60 days. After ensiling, silages with a normal DM were higher in pH, water-soluble carbohydrates (WSC) and DM loss (p < 0.05) when compared to silages ensiled at a moderately low DM. The higher DM content also limited proteolysis in silages indicated by lower concentrations of ammonia N (NH3 -N). Compared with the control group, MA and CA-treated silages had lower pH, lower concentrations of acetic acid and NH3 -N but higher concentrations of lactic acid. The addition of MA and CA reduced DM losses in silages when compared to the control group except for MA-treated silage at a moderately low DM in which only numerically lower DM loss was observed. Malic acid and CA also resulted in a higher proportion of polyunsaturated fatty acids, especially in silages with a moderately low DM. Including MA and CA could promote silage fermentation, limit proteolysis and lipolysis at the lower and medium-to-high end of DM contents in alfalfa silages.
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Medicago sativa , Silagem , Animais , Ácido Cítrico/farmacologia , Fermentação , Lipólise , Medicago sativa/química , Proteólise , Silagem/análiseRESUMO
BACKGROUND: It is widely acknowledged that childhood adversities (CAs) and recent stress are potential risk factors for adult depression. However, the mechanism(s) by which interactions of CAs with recent stress affect adult depression remain unclear. AIMS: To investigate the predictive association of the interaction among CAs and recent stress with early-adult depression. METHOD: We conducted an annual survey of all freshmen for the period of 2016-2018 in a Chinese comprehensive university, with a sample size of 23,206. An online questionnaire including standardized self-report instruments was used to assess sociodemographic factors, childhood experiences of left-behind (CELB), and maltreatments (CEMTs) including beating (CEB), neglect (CEN), sexual abuse (CESA), recent stress, and current depression (measured by the 9-item Patient Health Questionnaire). RESULTS: The correlation of Individual CAs and recent stress was significant. In addition to their significant independent/direct incremental effects, all surveyed CAs were associated with increased severity of early-adult depression, and increased frequency of clinically significant depression (CSD), through significant associations with recent stress (mediation effect). History of CEMTs including CEB, CEN, and CESA significantly increased the effects of recent stress on depression (moderation effect). CONCLUSIONS: Chinese undergraduate students reported frequent history of exposure to CAs, which increased the likelihood of depression in early adulthood, not only directly but also through the increasing the likelihood (mediation effect) and impact (moderation effect) of recent stress on depression. These novel findings may help to extend our understanding of environmental determinants of depression, and to guide further research, clinical practice, and policy in this context.
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Maus-Tratos Infantis , Depressão , Adulto , Criança , China/epidemiologia , Depressão/epidemiologia , Humanos , Autorrelato , EstudantesRESUMO
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.
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Transtornos Psicóticos , Esquizofrenia , Criança , Estudos Transversais , Alucinações/diagnóstico , Alucinações/epidemiologia , Humanos , Masculino , Prevalência , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologiaRESUMO
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.
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Transtornos Psicóticos , China/epidemiologia , Estudos Transversais , Humanos , Transtornos Paranoides , Transtornos Psicóticos/epidemiologia , População UrbanaRESUMO
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.