Shared and distinct electroencephalogram microstate abnormalities across schizophrenia, bipolar disorder, and depression.

BACKGROUND: Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear. METHODS: This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design. RESULTS: Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups. CONCLUSIONS: Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.

Dynamic aberrances of substantia nigra-relevant coactivation patterns in first-episode treatment-naïve patients with schizophrenia.

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.

Neural variability in three major psychiatric disorders.

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.

Interactions between overweight/obesity and alcohol dependence impact human brain white matter microstructure: evidence from DTI.

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk.

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.

Association of the plasma complement system with brain volume deficits in bipolar and major depressive disorders.

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.

Dynamic structure-function coupling across three major psychiatric disorders.

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.

Structural Covariance of Depth-Dependent Intracortical Myelination in the Human Brain and Its Application to Drug-Naïve Schizophrenia: A T1w/T2w MRI Study.

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.

Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene.

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.

The pattern glare and visual memory are disrupted in patients with major depressive disorder.

BACKGROUND: Visual memory impairment is one of the most commonly complained symptoms in patients with major depressive disorder (MDD). Pattern glare is also a distorted visual phenomenon that puzzles patients with MDD. Nevertheless, how these two phenomena interact in MDD remains unknown. This study investigated the association between pattern glare and visual memory in MDD patients. METHODS: Sixty-two patients with MDD and forty-nine age-, sex- and education level-matched healthy controls (HCs) were included in this study. The Pattern Recognition Memory (PRM) test and the Brief Visual Memory Test-Revised (BVMT-R) were applied to measure visual memory. The pattern glare test including three patterns with different spatial frequencies (SFs) was used to explore pattern glare levels. RESULTS: Patients with MDD scored lower on the PRM-PCi, BVMT-R1, BVMT-R2, BVMT-R3, and BVMT-Rt and higher on the PRM-MCLd than HCs (all p < 0.05). Pattern glare scores for MDD patients were higher with mid-SF (p < 0.001), high-SF (p = 0.006) and mid-high SF differences (p = 0.01) than for HCs. A positive correlation between mid-SF and PRM-MCLd scores in all participants was observed (p = 0.01, r = 0.246). A negative correlation between mid-high difference scores and BVMT-R2 scores (p = 0.032, r = -0.317) was observed in HCs, but no significant correlation was observed in MDD patients. CONCLUSIONS: The present study showed that visual memory and pattern glare are disrupted in MDD. Visual memory may be associated with pattern glare and needs to be studied in future work.

Data-driven study on resting-state functional magnetic resonance imaging during early abstinence of alcohol dependence in male patients and its predictive value for relapse.

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.

Automated Digital Interventions and Smoking Cessation: Systematic Review and Meta-analysis Relating Efficiency to a Psychological Theory of Intervention Perspective.

BACKGROUND: Smoking remains a highly significant preventable global public health problem. In this context, digital interventions offer great advantages in terms of a lack of biological side effects, possibility of automatic delivery, and consequent human resource savings relative to traditional interventions. Such interventions have been studied in randomized controlled trials (RCTs) but have not been systematically reviewed with the inclusion of text-based and multiplatform-based interventions. In addition, this area has not been evaluated from the perspective of the psychological theoretical basis of intervention. OBJECTIVE: The aim of this paper is to assess the efficiency of digital interventions in RCT studies of smoking cessation and to evaluate the effectiveness of the strategies used for digital interventions. METHODS: An electronic search of RCTs was conducted using PubMed, Embase, and the Cochrane Library by June 30, 2021. Eligible studies had to compare automated digital intervention (ADI) to the use of a self-help guideline or no intervention. Participants were current smokers (aged 16 years or older). As the main outcome, abstinence after endpoint was extracted from the studies. Systematic review and meta-analysis were conducted to assess the efficiency of ADIs. Metaregressions were conducted to assess the relationship between intervention theory and effectiveness. RESULTS: A total of 19 trials (15,472 participants) were included in the analysis. The overall abstinence rate (95% CI) at the endpoint was 17.8% (17.0-18.7). The overall risk ratio of the intervention group compared to the controls at the endpoint was 17.8% (17.0-18.7). Cochrane risk-of-bias tool for randomized trials (ROB 2) suggested that most of the studies had a low risk of bias (56.3%). Psychological theory-related constructs or predictors, which refer to other theory-based concepts (rather than only behavioral theory) such as craving or anxiety, are associated with effectiveness. CONCLUSIONS: This study found that ADI had a clear positive effect compared to self-help guidelines or to no intervention, and effectiveness was associated with theory-related constructs or predictors. ADIs should be promoted by policy makers and clinical practitioners to address the huge gap between the need for smoking cessation and availability of traditional treatment resources. Possible increases in ADI efficiency may be achieved by optimally integrating psychotherapeutic theories and techniques. TRIAL REGISTRATION: PROSPERO CRD42021256593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=256593.

A brief web-based screening plus emotional-disorder health education was associated with improvement of mental health awareness and service-seeking attitudes among patients seeking nonpsychiatric clinical services in China.

OBJECTIVES: Low recognition and intervention rates of emotional disorders among nonpsychiatric clinical patients are primarily attributable to poor mental health awareness of patients and a paucity of mental health care resources. This study aims to investigate the association of a resource-saving brief web-based emotional-disorder self-screening plus a health self-education program (BWBED-SS + HSE) with improved mental health awareness and service-seeking attitudes among nonpsychiatric clinical patients. METHOD: A sample of 2065 patients seeking health services in nonpsychiatric clinical settings underwent BWBED-SS + HSE using mobile terminals. Participants were defined as being at high risk of anxiety and/or depression according to the optimal cut-off point of ≥11 on the Huaxi emotional-distress index (HEI). RESULTS: The rate of participants at high risk of anxiety and/or depression was 6.63%. Following participation in the BWBED-SS + HSE, after controlling for demographics, type of hospital, and test time, the rates of participants considering themselves as having an emotional disorder and willing to seek mental health services among those at high risk of anxiety and/or depression increased from 29.93% to 47.45% (adjusted odds ratio [aOR] = 2.28, p = .002) and from 11.68% to 29.93% (aOR = 3.65, p < .001), respectively. CONCLUSIONS: The BWBED-SS + HSE were associated with improved mental health awareness and service-seeking attitudes among patients seeking nonpsychiatric clinical services in China.

The interactions between childhood adversities and recent stress were associated with early-adulthood depression among Chinese undergraduate students.

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.

Lower regional grey matter in alcohol use disorders: evidence from a voxel-based meta-analysis.

BACKGROUND: Previous research using whole-brain neuroimaging techniques has revealed structural differences of grey matter (GM) in alcohol use disorder (AUD) patients. However, some of the findings diverge from other neuroimaging studies and require further replication. The quantity of relevant research has, thus far, been limited and the association between GM and abstinence duration of AUD patients has not yet been systematically reviewed. METHODS: The present research conducted a meta-analysis of voxel-based GM studies in AUD patients published before Jan 2021. The study utilised a whole brain-based d-mapping approach to explore GM changes in AUD patients, and further analysed the relationship between GM deficits, abstinence duration and individual differences. RESULTS: The current research included 23 studies with a sample size of 846 AUD patients and 878 controls. The d-mapping approach identified lower GM in brain regions including the right cingulate gyrus, right insula and left middle frontal gyrus in AUD patients compared to controls. Meta-regression analyses found increasing GM atrophy in the right insula associated with the longer mean abstinence duration of the samples in the studies in our analysis. GM atrophy was also found positively correlated with the mean age of the samples in the right insula, and positively correlated with male ratio in the left middle frontal gyrus. CONCLUSIONS: GM atrophy was found in the cingulate gyrus and insula in AUD patients. These findings align with published meta-analyses, suggesting they are potential deficits for AUD patients. Abstinence duration, age and gender also affect GM atrophy in AUD patients. This research provides some evidence of the underlying neuroanatomical nature of AUD.

Lasting effects of residential mobility during childhood on psychopathology among Chinese University students.

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.

Testing extra-linearity across a psychosis continuum.

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.

Impact of urban birth and upbringing on expression of psychosis in a Chinese undergraduate population.

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.

Sustained effects of left-behind experience during childhood on mental health in Chinese university undergraduates.

Rapid industrialization and urbanization in China have resulted in labor migrants leaving children behind. For left-behind children (LBC), disrupted parental attachment may increase the risk of psychiatric morbidity in adulthood. To investigate psychopathological consequences for university students who were LBC and to estimate the effects of one or both parents being migrants, the duration of left-behind experience, and parental absence during critical periods of growth on psychiatric morbidity. We conducted an annual survey of all freshmen at a Chinese university from 2014 to 2018. The questionnaire collected information on left-behind experiences and psychiatric morbidity using standardized self-report instruments. Regression coefficients derived from logistic regression were used to measure the associations among total time left behind, absence of one parent or both parents, age when left behind and psychopathological consequences. A total of 42,505 students were included. Students who were LBC had more psychopathology, including depression, anxiety, somatoform disorder, obsessive-compulsive disorder, self-reported suicide attempts and deliberate self-harm, than those who were not. Students for whom one or both parents were migrants showed a greater risk of psychiatric morbidity. The risk of psychiatric morbidity increased with the length of parental absence. Left-behind experience during childhood represents sustained impacts for university students into early adulthood. The higher prevalence of psychiatric morbidity in young adults who experienced the absence of one or both of their parents, especially in their early childhood, suggests that other factors besides attachment, such as protection from other risks, are important and that further research is necessary.

CtBP1 transactivates RAD51 and confers cisplatin resistance to breast cancer cells.

Overexpression of RAD51 is found in many cancers including breast cancer and is associated with poor survival. Compared with normal cells, RAD51 promoter is hyperactive in cancer cells indicating that RAD51 is transcriptionally activated. However, little is known about the mechanisms and factors involved in RAD51 transcription regulation. Transcription corepressor, C-terminal binding protein 1 (CtBP1), is an oncogene repressing a panel of tumor suppressors transcription, which contributes to cancer progression. In this study, immunohistochemistry (IHC) revealed that RAD51 expression was positively correlated with CtBP1 expression in breast cancer patient tissues; short hairpin RNA-mediated CtBP1 depletion, chromatin immunoprecipitation, and dual-luciferase reporter assays showed that CtBP1 activated RAD51 transcription in breast cancer cells. Depletion of CtBP1 increased breast cancer cells' sensitivity to cisplatin and, in turn, expression of exogenous RAD51 in the CtBP1-depleted breast cancer cells increased resistance to cisplatin. The results demonstrated that CtBP1 conferred breast cancer cells resistance to cisplatin through transcriptional activation of RAD51.