Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders.

BACKGROUND: Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine. METHODS: We recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort. RESULTS: Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable. CONCLUSIONS: Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.

Dysregulated cerebral blood flow, rather than gray matter Volume, exhibits stronger correlations with blood inflammatory and lipid markers in depression.

Arterial spin labeling (ASL) can be used to detect differences in perfusion for multiple brain regions thought to be important in major depressive disorder (MDD). However, the potential of cerebral blood flow (CBF) to predict MDD and its correlations between the blood lipid levels and immune markers, which are closely related to MDD and brain function change, remain unclear. The 451 individuals - 298 with MDD and 133 healthy controls who underwent MRI at a single time point with arterial spin labelling and a high resolution T1-weighted structural scan. A proportion of MDD also provided blood samples for analysis of lipid and immune markers. We performed CBF case-control comparisons, random forest model construction, and exploratory correlation analyses. Moreover, we investigated the relationship between gray matter volume (GMV), blood lipids, and the immune system within the same sample to assess the differences in CBF and GMV. We found that the left inferior parietal but supramarginal and angular gyrus were significantly different between the MDD patients and HCs (voxel-wise P < 0.001, cluster-wise FWE correction). And bilateral inferior temporal (ITG), right middle temporal gyrus and left precentral gyrus CBF predict MDD (the area under the receiver operating characteristic curve of the random forest model is 0.717) and that CBF is a more sensitive predictor of MDD than GMV. The left ITG showed a positive correlation trend with immunoglobulin G (r = 0.260) and CD4 counts (r = 0.283). The right ITG showed a correlation trend with Total Cholesterol (r = -0.249) and tumour necrosis factor-alpha (r = -0.295). Immunity and lipids were closely related to CBF change, with the immunity relationship potentially playing a greater role. The interactions between CBF, plasma lipids and immune index could therefore represent an MDD pathophysiological mechanism. The current findings provide evidence for targeted regulation of CBF or immune properties in MDD.

Striatum-related spontaneous coactivation patterns predict treatment response on positive symptoms of drug-naive first-episode schizophrenia with risperidone monotherapy.

Background: Evidence from functional magnetic resonance imaging (fMRI) studies of schizophrenia suggests that interindividual variation in the stationary striatal functional circuit may be correlated with antipsychotic treatment response. However, little is known about the role of the dynamic striatum-related network in predicting patients' clinical improvement. The spontaneous coactivation pattern (CAP) technique has recently been found to be important for elucidating the non-stationary nature of functional brain networks. Methods: Forty-two drug-naive first-episode schizophrenia patients underwent fMRI and T1W imaging before and after 8 weeks of risperidone monotherapy. The striatum was divided into 3 subregions, including the putamen, pallidum, and caudate. Spontaneous CAPs and CAP states were utilized to measure the dynamic characteristics of brain networks. We used DPARSF and Dynamic Brain Connectome software to analyze each subregion-related CAP and CAP state for each group and then compared the between-group differences in the neural network biomarkers. We used Pearson's correlation analysis to determine the associations between the neuroimaging measurements with between-group differences and the improvement in patients' psychopathological symptoms. Results: In the putamen-related CAPs, patients showed significantly increased intensity in the bilateral thalamus, bilateral supplementary motor areas, bilateral medial, and paracingulate gyrus, left paracentral lobule, left medial superior frontal gyrus, and left anterior cingulate gyrus compared with healthy controls. After treatment, thalamic signals in the putamen-related CAP 1 showed a significant increase, while the signals of the medial and paracingulate gyrus in the putamen-related CAP 3 revealed a significant decrease. The increase in thalamic signal intensity in the putamen-related CAP 1 was significantly and positively correlated with the percentage reduction in PANSS_P. Conclusion: This study is the first to combine striatal CAPs and fMRI to explore treatment response-related biomarkers in the early phase of schizophrenia. Our findings suggest that dynamic changes in CAP states in the putamen-thalamus circuit may be potential biomarkers for predicting patients' variation in the short-term treatment response of positive symptoms.

Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics.

Background: Antipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications. Methods: Utilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement. Results: We detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms. Conclusions: This study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a "three-step" roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.

Epigenetic clock analysis of blood samples in drug-naive first-episode schizophrenia patients.

BACKGROUND: Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. METHODS: We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. RESULTS: Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. CONCLUSION: These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Anhedonia and dysregulation of an angular gyrus-centred and dynamic functional network in adolescent-onset depression.

BACKGROUND: Anhedonia is an important aspect of adolescent-onset major depressive disorder (MDD) and is associated with increased risk of suicidal behaviors and poor treatment outcomes. However, the neural circuitry underlying this deficit has not been well defined. This study aims to identify the relationships between anhedonia and changes in static and dynamic functional connectivity (FC) in adolescent-onset MDD patients compared with healthy control subjects (HCs) and adult-onset MDD patients. METHODS: A total of 157 participants completed the Snaith-Hamilton Pleasure Scale (SHAPS) to assess hedonic capacity. Resting-state functional imaging scans were analysed using graph theoretical analysis, network-based statistics (NBS) and sliding window correlation analysis to explore the potential patterns of neural network brain disruptions in adolescent-onset MDD. Pearson correlations and support vector machines regression (SVR) were used to explore correlations and predict network measures with SHAPS scores. RESULTS: Compared with those with adult-onset MDD, adolescent-onset MDD patients showed decreased FC in 7 nodes and 6 connections, with the right angular gyrus (AG), left AG and left paracentral lobule having the largest number of connected edges (P = 0.0396, NBS-corrected). Their average FC and SHAPS scores were positively correlated (r = 0.309, P = 0.035). Regarding dynamic FC, compared with HCs, adolescent-onset MDD patients showed a tendency towards a decreased frequency in moderate-intensity brain FC states (P = 0.014), which was significantly and positively correlated with SHAPS scores (r = 0.425, P = 0.003). SVR also revealed AG-centred FC and dynamic FC could predict SHAPS scores (MSE = 27.233, P = 0.001). CONCLUSIONS: These findings provide distinct evidence on the physiological mechanisms of adolescent-onset MDD and anhedonia.

Virtual histology of morphometric similarity network after risperidone monotherapy and imaging-epigenetic biomarkers for treatment response in first-episode schizophrenia.

BACKGROUND: Antipsychotic treatment has been conceived to alter brain connectivity, but it is unclear how the changes of network phenotypes relate to the underlying transcriptomics. Given DNA methylation (DNAm) may alter transcriptional levels, we further integrated an imaging-transcriptomic-epigenetic analysis to explore multi-omics treatment response biomarkers. METHODS: Forty-two treatment-naive first-episode schizophrenia patients were scanned by TI weighted (T1W) imaging and DTI before and after 8-week risperidone monotherapy, and their peripheral blood genomic DNAm values were examined in parallel with MRI scanning. Morphometric similarity network (MSN) quantified with DTI and T1W data were used as a marker of treatment-related alterations in interareal cortical connectivity. We utilized partial least squares (PLS) to examine spatial associations between treatment-related MSN variations and cortical transcriptomic data obtained from the Allen Human Brain Atlas. RESULTS: Longitudinal MSN alterations were related to treatment response on cognitive function and general psychopathology symptoms, while DNAm values of 59 PLS1 genes were on negative and positive symptoms. Virtual-histology transcriptomic analysis linked the MSN alterations with the neurobiological, cellular and metabolic pathways or processes, and assigned MSN-related genes to multiple cell types, specifying neurons and glial cells as contributing most to the transcriptomic associations of longitudinal changes in MSN. CONCLUSIONS: We firstly reveal how brain-wide transcriptional levels and cell classes capture molecularly validated cortical connectivity alterations after antipsychotic treatment. Our findings represent a vital step towards the exploration of treatment response biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.

Superior temporal gyrus and cerebellar loops predict nonsuicidal self-injury in major depressive disorder patients by multimodal neuroimaging.

In major depressive disorder (MDD) patients, nonsuicidal self-injury (NSSI) is a common comorbidity, and it is important to clarify the underlying neurobiology. Here, we investigated the association of NSSI with brain function and structure in MDD patients. A total of 260 MDD patients and 132 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and three-dimensional T1-weighted structural scans. NSSI behaviour was assessed through interviews. Voxel-based morphometry analysis (VBM), regional homogeneity analysis (ReHo), functional connectome topology properties and network-based statistics were used to detect the differences in neuroimaging characteristics. Finally, the random forest method was used to evaluate whether these factors could predict NSSI in MDD. Compared with HCs, MDD patients with a history of NSSI showed significant right putamen grey matter volume (GMV), right superior orbital frontal cortex ReHo, left pallidum degree centrality, and putamen-centre function network differences. Compared to MDD subjects without NSSI, those with past NSSI showed significant right superior temporal gyrus (STG) GMV, right lingual gyrus ReHo, sigma and global efficiency, and cerebellum-centre function network differences. The right STG GMV and cerebellum-centre function network were more important than other factors in predicting NSSI behaviour in MDD. MDD patients with a history of NSSI have dysregulated spontaneous brain activity and structure in regions related to emotions, pain regulation, and the somatosensory system. Importantly, right STG GMV and cerebellar loops may play important roles in NSSI in MDD patients.

Risperidone-induced changes in DNA methylation in peripheral blood from first-episode schizophrenia patients parallel changes in neuroimaging and cognitive phenotypes.

BACKGROUND: Second generation antipsychotics such as risperidone are first-line pharmacotherapy treatment choices for schizophrenia. However, our ability to reliably predict and monitor treatment reaction is impeded by the lack of relevant biomarkers. As a biomarker for the susceptibility of schizophrenia and clozapine treatment response, DNA methylation (DNAm) has been studied, but the impact of antipsychotics on DNAm has not been explored in drug-naïve patients. OBJECTIVE: The aim of the present study was to examine changes of DNAm after short-term antipsychotic therapy in first-episode drug-naïve schizophrenia (FES) to identify the beneficial and adverse effect of risperidone on DNAm and their relation to treatment outcome. METHODS: Thirty-eight never treated schizophrenia patients and 38 demographically matched individuals (healthy controls) were assessed at baseline and at 8-week follow-up with symptom ratings, and cognitive and functional imaging procedures, at which time a blood draw for DNAm studies was performed. During the 8-week period, patients received treatment with risperidone monotherapy. An independent data set was used as replication. RESULTS: We identified brain related pathways enriched in 4,888 FES-associated CpG sites relative to controls. Risperidone administration in patients altered DNAm in 5,979 CpG sites relative to baseline. Significant group differences in DNAm at follow-up were seen in FES patients at 6,760 CpG sites versus healthy controls. Through comparison of effect size, we found 87.54% out of the risperidone-associated changes in DNAm showed possible beneficial effect, while only 12.46% showed potential adverse effect. There were 580 DNAm sites in which changes shifted methylation levels to be indistinguishable from controls after risperidone treatment. The DNAm changes of some sites that normalized after treatment were correlated with treatment-related changes in symptom severity, spontaneous neurophysiological activity, and cognition. We replicated our results in an independent data set. CONCLUSION: The normalizing effect of risperidone monotherapy on gene DNAm, and its correlation with clinically relevant phenotypes, indicates that risperidone therapy is associated with DNAm changes that are related to changes in brain physiology, cognition and symptom severity.

Predictive Biomarkers for Antipsychotic Treatment Response in Early Phase of Schizophrenia: Multi-Omic Measures Linking Subcortical Covariant Network, Transcriptomic Signatures, and Peripheral Epigenetics.

Background: Volumetric alterations of subcortical structures as predictors of antipsychotic treatment response have been previously corroborated, but less is known about whether their morphological covariance relates to treatment outcome and is driven by gene expression and epigenetic modifications. Methods: Subcortical volumetric covariance was analyzed by using baseline T1-weighted magnetic resonance imaging (MRI) in 38 healthy controls and 38 drug-naïve first-episode schizophrenia patients. Patients were treated with 8-week risperidone monotherapy and divided into responder and non-responder groups according to the Remission in Schizophrenia Working Group (RSWG). We utilized partial least squares (PLS) regression to examine the spatial associations between gene expression of subcortical structures from a publicly available transcriptomic dataset and between-group variances of structural covariance. The peripheral DNA methylation (DNAm) status of a gene of interest (GOI), overlapping between genes detected in the PLS and 108 schizophrenia candidate gene loci previously reported, was examined in parallel with MRI scanning. Results: In the psychotic symptom dimension, non-responders had a higher baseline structural covariance in the putamen-hippocampus-pallidum-accumbens pathway compared with responders. For disorganized symptoms, significant differences in baseline structural covariant connections were found in the putamen-hippocampus-pallidum-thalamus circuit between the two subgroups. The imaging variances related to psychotic symptom response were spatially related to the expression of genes enriched in neurobiological processes and dopaminergic pathways. The DNAm of GOI demonstrated significant associations with patients' improvement of psychotic symptoms. Conclusion: Baseline subcortical structural covariance and peripheral DNAm may relate to antipsychotic treatment response. Phenotypic variations in subcortical connectome related to psychotic symptom response may be transcriptomically and epigenetically underlaid. This study defines a roadmap for future studies investigating multimodal imaging epigenetic biomarkers for treatment response in schizophrenia.

Dysfunctional Attitudes Mediate the Relationship Between Childhood Emotional Neglect and Anhedonia in Young Adult Major Depression Patients.

BACKGROUND: Childhood traumas are well-established risk factors for major depressive disorder (MDD). However, the relationship between childhood traumas types and MDD symptoms is unclear. The present study tested the hypothesis that childhood traumas affect specific types of anhedonia in depression and the mediating role of dysfunctional attitude. METHODS: Within this cross-sectional study, 310 young adult patients with MDD completed the PHQ-9, CTQ-SF, DAS, and SHAPS. The statistical analyses used the Mann-Whitney U test, Spearman's rank correlation, and multiple regression analysis. Mediation analyses were tested by the structural equation model (SEM). RESULTS: Spearman's rank correlation analysis showed positive correlations between the SHAPS, CTQ-SF, and DAS total score (p < 0.05). The EA, EN, PN, and SHAPS scores were positively correlated (p < 0.05). Among the four factors of anhedonia, social interaction and interest/pastimes were positively correlated with EA, EN, and PN (p < 0.05), the sensory experience was positively correlated with EN (p < 0.01), and diet did not correlate with childhood traumas. Stepwise regression analysis showed that dysfunctional attitude and emotional neglect were the main influencing factors of sensory experience (p < 0.001) and social interaction (p < 0.001). Dysfunctional attitude and physical neglect were the main factors influencing interest/pastimes (p < 0.001). SEM analysis found that dysfunctional mediated between childhood traumas and anhedonia. CONCLUSIONS: The degree of anhedonia was related to dysfunctional attitudes and childhood traumas. The childhood emotional neglect experience was the most important and was related to sensory and social anhedonia. Dysfunctional attitudes played a mediating role between childhood neglect and anhedonia. Early psychotherapy targeting young adult MDD patients with childhood emotional neglect may help decrease symptoms of anhedonia.

Tracking Positive and Negative Symptom Improvement in First-Episode Schizophrenia Treated with Risperidone Using Individual-Level Functional Connectivity.

Background: To improve treatment outcomes of patients with schizophrenia, research efforts have focused on identifying brain-based markers of treatment response. Personal characteristics regarding disease-related behaviors likely stem from interindividual variability in the organization of brain functional systems. This study aimed to track dimension-specific changes in psychotic symptoms following risperidone treatment using individual-level functional connectivity (FC). Methods: A reliable cortical parcellation approach that accounts for individual heterogeneity in cortical functional anatomy was used to localize functional regions in a longitudinal cohort consisting of 42, drug-naive, first-episode schizophrenia (FES) patients at baseline and after 8 weeks of risperidone treatment. FC was calculated in individually specified brain regions and used to predict the baseline severity and improvement of positive and negative symptoms in FES. Results: Distinct sets of individual-specific FC were separately associated with the positive and negative symptom burden at baseline, which could be used to track the corresponding symptom resolution in FES patients following risperidone treatment. Between-network connections of the fronto-parietal network (FPN) contributed the most to predicting the positive symptom domain. A combination of between-network connections of the default mode network, FPN, and within-network connections of the FPN contributed markedly to the prediction model of negative symptoms. Conclusion: This novel study, which accounts for individual brain variation, takes a step toward establishing individual-specific theranostic biomarkers in schizophrenia. Impact statement This study revealed a theranostic marker for personalized medicine in schizophrenia and may aid in circuit-specific therapies for this disorder.

DNA Methylation Basis in the Effect of White Matter Integrity Deficits on Cognitive Impairments and Psychopathological Symptoms in Drug-Naive First-Episode Schizophrenia.

Background: Mounting evidence from diffusion tensor imaging (DTI) and epigenetic studies, respectively, confirmed the abnormal alterations of brain white matter integrity and DNA methylation (DNAm) in schizophrenia. However, few studies have been carried out in the same sample to simultaneously explore the WM pathology relating to clinical behaviors, as well as the DNA methylation basis underlying the WM deficits. Methods: We performed DTI scans in 42 treatment-naïve first-episode schizophrenia patients and 38 healthy controls. Voxel-based method of fractional anisotropy (FA) derived from DTI was used to assess WM integrity. Participants' peripheral blood genomic DNAm status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with DTI scanning. Participants completed Digit Span test and Trail Making test, as well as Positive and Negative Syndrome Scale measurement. We acquired genes that are differentially expressed in the brain regions with abnormal FA values according to the Allen anatomically comprehensive atlas, obtained DNAm levels of the corresponding genes, and then performed Z-test to compare the differential epigenetic-imaging associations (DEIAs) between the two groups. Results: Significant decreases of FA values in the patient group were in the right middle temporal lobe WM, right cuneus WM, right anterior cingulate WM, and right inferior parietal lobe WM, while the significant increases were in the bilateral middle cingulate WM (Ps < 0.01, GRF correction). Abnormal FA values were correlated with patients' clinical symptoms and cognitive impairments. In the DEIAs, patients showed abnormal couple patterns between altered FA and DNAm components, for which the enriched biological processes and pathways could be largely grouped into three biological procedures: the neurocognition, immune, and nervous system. Conclusion: Schizophrenia may not cause widespread neuropathological changes, but subtle alterations affecting local cingulum WM, which may play a critical role in positive symptoms and cognitive impairments. This imaging-epigenetics study revealed for the first time that DNAm of genes enriched in neuronal, immunologic, and cognitive processes may serve as the basis in the effect of WM deficits on clinical behaviors in schizophrenia.

The Patient Health Questionnaire-9 vs. the Hamilton Rating Scale for Depression in Assessing Major Depressive Disorder.

Background: The Hamilton Rating Scale for Depression (HAMD-17) has been used for several decades to assess the severity of depression. Multiple studies have documented defects in this scale and deemed it unsuitable for clinical evaluation. The HAMD-6, which is the abbreviated version of HAMD-17, has been shown to be effective in assessing the core symptoms of depression with greater sensitivity than HAMD-17. And the Patient Health Questionnaire-9 (PHQ-9) is suggested as an effective alternative to the HAMD-17 because of its simplicity and ease-of-use. Methods: Research was completed involving 1,741 participants having major depressive disorder. Cronbach's alpha, intraclass correlation coefficient (ICC) and weighted Kappa analysis was used to determine the reliability of the scales. Pearson correlation analysis and factor analysis were used to analyze validity. Item response theory (IRT) was used to analyze psychological characteristics of items in both the HAMD-17 and PHQ-9. Results: Reliability analysis showed that the Cronbach's alpha of the HAMD-17, HAMD-6 and PHQ-9 were 0.829, 0.764, and 0.893 respectively, and the ICC of the three scales ranged from 0.606 to 0.744. The Kappa score of the consistency of depression severity assessment was 0.248. Validity analysis showed that the PHQ-9 was a single factor structure, and the total score of the scale was strongly correlated with the HAMD-17 (r = 0.724, P < 0.001). The IRT analysis showed that the discrimination parameters of the PHQ-9 were higher than that of the HAMD-17 in all dimensions. The HAMD-6 had the lowest measurement accuracy in distinguishing the severity of depression, while the PHQ-9 had the highest measurement accuracy. Conclusion: Results showed that the PHQ-9 was satisfactory in terms of reliability, validity and distinguishing the severity of depression. It is a simple, rapid, effective and reliable tool which can be used as an alternative to the HAMD-17 to assess the severity of depression.

The Interaction Effects of Suicidal Ideation and Childhood Abuse on Brain Structure and Function in Major Depressive Disorder Patients.

Suicidal ideation (SI) is a direct risk factor for suicide in patients with depression. Regarding the emergence of SI, previous studies have discovered many risk factors, including childhood abuse as the major public problem. Previous imaging studies have demonstrated that SI or childhood abuse has effects on brain structure and function, respectively, but the interaction effects between them have not been fully studied. To explore the interaction effect between SI and childhood abuse, 215 patients with major depressive disorder completed the Childhood Trauma Questionnaire to evaluate childhood abuse and Beck's Scale for Suicidal Ideation to evaluate SI. Then, they completed magnetic resonance imaging (MRI) within one week after completing questionnaires. Respectively, we preprocessed the structural and functional images and analyzed gray matter volumes (GMV) and mean fractional amplitude of low-frequency fluctuation (mfALFF) values. Results showed that the changes of GMV in the cuneus, precuneus, paracentric lobule, inferior frontal gyrus, and caudate nucleus and local activity in cuneal and middle temporal gyrus are in relation with SI and childhood abuse. And in left caudate, SI and childhood abuse interact with each other on the influence of GMV. That is, the influence of SI in GMV was related to childhood abuse, and the influence of childhood abuse in GMV was also related to SI. Therefore, the combination of SI and childhood abuse based on imaging should help us better understand the suicide ideation developing mechanism and propose more effective targeted prevention strategies for suicide prevention.

Prevalence and Risk Factors Associated with Insomnia Symptoms Among the Chinese General Public After the Coronavirus Disease 2019 Epidemic Was Initially Controlled.

INTRODUCTION: The prevalence rate and related factors of insomnia remained unknown after the COVID-19 epidemic had been under control. Therefore, we conducted this survey to investigate the prevalence rate and related factors of insomnia symptoms in the Chinese general public after the COVID-19 had been initially control. METHODS: An online survey was conducted among Chinese citizens through the JD Health APP. The questionnaire was used for collecting demographic data and self-designed questions related to the COVID-19 outbreak. Insomnia Severity Index, Patient Health Questionnaire-9, Somatic Symptom Scale-8 and Impact of Events Scale-Revised were used for measuring psychological symptoms. To examine the associations of sociodemographic and psychological factors with insomnia symptoms, a binary logistic regression was used. RESULTS: In total, there were 14,894 eligible participants, and 4601 (30.9%) participants were found to have insomnia symptoms. The regression model revealed that a higher risk of insomnia symptoms was associated with being over the age of 40 years, having history of psychiatric disorders, smoking, having infected friends or colleagues, having depressive or somatic symptoms, experiencing psychological distress and feeling estranged from family members. Meanwhile a lower risk of insomnia symptoms was associated with being female, having closer family relationships, not feeling alienated from others and being satisfied with the available information. CONCLUSION: In our study, 30.9% of the participants in the general public reported insomnia symptoms after the COVID-19 epidemic had been initially controlled. When providing precise interventions for insomnia, extra attention should be paid to the individuals who are male, elderly and smokers, and those with psychiatric disorder history, with infected friends or colleagues, with psychological symptoms and with poor social support.

Nonsuicidal self-injury in undergraduate students with major depressive disorder: The role of psychosocial factors.

BACKGROUND: Nonsuicidal self-injury (NSSI) is related to childhood abuse, family relationships, interpersonal relationships, personality, but the interaction between them is still unclear, and how they interact in major depressive disorder (MDD). METHODS: Collected data from 444 undergraduate degree students with MDD participated. Used the Eysenck Personality Questionnaire, Childhood Trauma Questionnaire, Interpersonal Relationship Comprehensive Diagnostic Scale, and Family Assessment Device to assess the patients' psychosocial factors. NSSI behavior was assessed through interviews. Use the Chi-square test, Wilcoxon rank-sum test, Kruskal-Wallis H-test, Distance Correlation, Structural Equation Mode for data analysis. RESULTS: Overall, 34.2% of patients with MDD had a history of NSSI. MDD patients with a history of NSSI had significant differences in psychoticism, neuroticism, emotional abuse, physical abuse, sexual abuse, emotional neglect, troubles in conversation, ability to make friends and family roles. Among these factors, psychoticism was most related to NSSI, and child abuse, interpersonal relationships and family roles played a variety of roles in mediating the relationship with NSSI. CONCLUSIONS: Psychosocial factors affect the occurrence of NSSI through chain intermediary effects.

Effects of risperidone monotherapy on the default-mode network in antipsychotic-naïve first-episode schizophrenia: Posteromedial cortex heterogeneity and relationship with the symptom improvements.

The default mode network (DMN) has been consistently detected abnormally in schizophrenia. However, the effects of antipsychotics on this network are still under debate, and inconsistent findings may be due to the functional heterogeneity within the DMN, especially in the component regions of the posteromedial cortex (PMC). Here, we conducted a longitudinal research on the resting-state functional connectivity of the PMC subdivisions on 33 treatment-naive first-episode patients with schizophrenia at baseline and after 8 weeks of risperidone treatment through resting-state functional magnetic resonance imaging. At baseline, the patients demonstrated decreased connectivity of the three PMC seeds with several brain regions (target regions) compared with healthy controls. We then tested the effect of antipsychotic treatment on the functional connectivity between the three seeds and the target regions. We found that, one of the three seeds encompassed in PMC, namely, posterior cingulate cortex (PCC), was observed to have increased functional connectivity with the bilateral thalamus and the left lingual gyrus (LG). On the contrary, the functional connectivity between the target regions and the two remaining seeds, namely, the retrosplenial cortex and precuneus, was unaffected by risperidone treatment. Correlation analysis revealed a positive correlation between longitudinal change of PCC-LG connectivity and symptom improvement. These findings indicated the heterogeneity of the PMC in response to antipsychotic treatment and suggested the role of PCC as a treatment biomarker for schizophrenia.

Effect of Risperidone Monotherapy on Dynamic Functional Connectivity of Insular Subdivisions in Treatment-Naive, First-Episode Schizophrenia.

OBJECTIVE: The insula consists of functionally diverse subdivisions, and each division plays different roles in schizophrenia neuropathology. The current study aimed to investigate the abnormal patterns of dynamic functional connectivity (dFC) of insular subdivisions in schizophrenia and the effect of antipsychotics on these connections. METHODS: Longitudinal study of the dFC of insular subdivisions was conducted in 42 treatment-naive first-episode patients with schizophrenia at baseline and after 8 weeks of risperidone treatment based on resting-state functional magnetic resonance image (fMRI). RESULTS: At baseline, patients showed decreased dFC variance (less variable) between the insular subdivisions and the precuneus, supplementary motor area and temporal cortex, as well as increased dFC variance (more variable) between the insular subdivisions and parietal cortex, compared with healthy controls. After treatment, the dFC variance of the abnormal connections were normalized, which was accompanied by a significant improvement in positive symptoms. CONCLUSIONS: Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in schizophrenia and suggested that these abnormalities may be modified after antipsychotic treatment.

Distinct striatum pathways connected to salience network predict symptoms improvement and resilient functioning in schizophrenia following risperidone monotherapy.

Abnormal interactions between the striatum and salience network (SN) are considered as etiological and treatment-sensitive marker in schizophrenia. However, whether alterations in the intrinsic dynamics as reflected by resting-state functional connectivity (RSFC) between the striatum and salience network may predict treatment response to the widely used antipsychotic treatment strategies (risperidone, monotherapy) has not been examined systematically. To this end, treatment-naive first-episode schizophrenia patients (n = 41) underwent task-free resting-state fMRI assessment before (baseline) and after 8 weeks of risperidone monotherapy (n = 38). Intrinsic connectivity between striatal sub-regions and core salience processing nodes were examined and compared to carefully matched healthy controls (HC) to determine disorder-specific and treatment-predictive neural markers. Findings demonstrate hypo-connectivity of both ventral and dorsal striatal-SN pathways in patients at baseline. Importantly, specifically the dorsal striatal pathway at baseline could predict negative symptoms improvement in patients; while ventral striatal pathways could predict positive symptoms improvement. Together, results indicate that distinct striatal-SN pathways represent specific treatment-success markers for the effects of risperidone, suggesting that alterations in dorsal versus ventral striatal network markers may represent brain-based markers for specific symptomatologic improvements following risperidone mono-therapy.