Pathway from childhood trauma to nonsuicidal self-injury in adolescents with major depressive disorder: the chain-mediated role of psychological resilience and depressive severity.

This study aimed to explore the pathway from childhood trauma to nonsuicidal self-injury (NSSI) in adolescents with major depressive disorder (MDD) and to examine the chain-mediating role of psychological resilience and depressive symptoms in this pathway. A total of 391 adolescents with MDD were recruited in the present study. The Chinese version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Chinese version of the Symptoms Check List-90 (SCL-90), the Chinese version of the Conner-Davidson Resilience Scale (CD-RISC), and the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC) were used to evaluate childhood trauma, depressive symptoms, psychological resilience and NSSI, respectively. Our results showed that 60.87% of adolescents with MDD had NSSI in the past month. Childhood trauma frequency was negatively correlated with psychological resilience but positively correlated with depressive symptoms and NSSI severity in adolescents with MDD. The stepwise logistic regression analysis identified that age, childhood trauma and depressive symptoms could independently predict the occurrence of NSSI, and the three-step hierarchical regression showed that childhood trauma, psychological resilience and depressive symptoms were all significantly associated with NSSI frequency in adolescents with MDD. Furthermore, the chain-mediation analysis revealed that psychological resilience and depression serially mediated the relationship between childhood trauma and NSSI in adolescents with MDD. Interventions targeted at improving resilience and depression may mitigate the impact of childhood trauma severity on NSSI risk in adolescents with MDD.

Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder.

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

Rumination mediates the relationship between childhood trauma and depressive symptoms in schizophrenia patients.

Rumination and childhood trauma are related to depressive symptoms in clinical and non-clinical individuals. This is the first study aimed to test the mediating effect of rumination on the relationship between childhood trauma and depressive symptoms in schizophrenia patients. A total of 313 schizophrenia patients were recruited in the present study. The 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, the short-form Childhood Trauma Questionnaire (CTQ-SF) and the 10-item Ruminative response scale (RRS-10) were utilized to assess the childhood trauma and rumination in patients, respectively. Our results showed that 168 schizophrenia patients (53.67%) had comorbid depressive symptoms. These patients with depressive symptoms had higher levels of childhood trauma [both CTQ-SF total scores and emotional abuse (EA), emotional neglect (EN), physical neglect (PN) subscale scores] and rumination (both RRS-10 total scores and brooding, reflection subscale scores) compared to patients without depressive symptoms. The stepwise logistic regression analysis identified that EN (OR 1.196, P = 0.003), PN (OR 1.1294, P < 0.001), brooding (OR 1.291, P < 0.001) and reflection (OR 1.481, P < 0.001) could independently predict the depressive symptoms in schizophrenia patients. Moreover, RRS-10 and its subscale scores could mediate the relationship between depressive symptoms and childhood trauma, especially EA, EN and PN in schizophrenia. Our preliminary findings suggest that the rigorous assessment and psychosocial interventions of rumination are important to alleviate the influence of childhood trauma on depressive symptoms in schizophrenia patients.

Inflammatory cytokines, complement factor H and anhedonia in drug-naïve major depressive disorder.

OBJECTIVE: Anhedonia is a core symptom of major depressive disorder (MDD) and often associated with poor prognosis. The main objective of the present study was to explore the relationship between complement factor H (CFH), inflammatory cytokines and anhedonia in drug-naïve MDD patients. METHODS: A total of 215 participants (61 MDD patients with anhedonia, 78 MDD patients without anhedonia, and 76 control subjects) were included. Severity of depression and levels of anhedonia were evaluated by Hamilton Rating Scale for Depression-17 (HAMD-17) and SHAPS (Snaith-Hamilton Pleasure Scale). Plasma levels of CFH, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were measured. RESULTS: The plasma levels of CFH, IL-10 and TNF-α were higher in drug-naïve MDD patients than control subjects. Compared to MDD patients without anhedonia, patients with anhedonia showed higher levels of CFH and IL-6. The stepwise regression analysis revealed that IL-10, TNF-α, as well as IL-10 × TNF-α were associated with depressive symptoms measured by HAMD-17 in drug-naïve MDD patients, while only CFH levels were identified as a mediator factor for the severity of anhedonia in the patients. CONCLUSION: MDD patients with anhedonia showed different inflammatory characteristics compared to patients without anhedonia. Our results provide novel evidence suggesting that increased plasma CFH levels may be a potential biomarker of anhedonia of subtyping MDD.

A Novel Synthetic Interfering Peptide Tat-3L4F Attenuates Olanzapine-Induced Weight Gain Through Disrupting Crosstalk Between Serotonin Receptor 2C and Protein Phosphatase and Tensin Homolog in Rats.

BACKGROUND: Accompanied with profound efficacy, atypical antipsychotics (AAPs) contribute to metabolic adverse effects with few effective strategies to attenuate. Serotonin 5-HT2C receptor (HTR2C) plays a critical role in hyperphagia and weight gain induced by AAPs, and expression of phosphatase tensin homolog (PTEN) in the hypothalamus also affects feeding behavior and weight change. Moreover, PTEN has a physical crosstalk between PTEN and a region in the third intracellular loop (3L4F) of the HTR2C. Tat-3L4F has the property to disrupt crosstalk between PTEN and HTR2C. This is the first study to our knowledge to investigate the effect of Tat-3L4F on olanzapine-induced metabolic abnormalities and PTEN/ phosphatidylinositol 3-kinase/protein kinase B expression in the hypothalamus in rats. METHODS: The effects of Tat-3L4F were investigated through measuring body weight, food intake, and blood glucose. In addition, PTEN/phosphatidylinositol 3-kinase/protein kinase B level in the hypothalamus was detected by immunofluorescence assay and western blot. Metabolites in the liver tissue were detected by liquid chromatography-mass spectrometry and analyzed by multivariate analyses and pairwise comparison. RESULTS: Our results showed that hyperphagia and weight gain were evident in the olanzapine alone-fed rats but was attenuated after Tat-3L4F treatment. In addition, oral glucose tolerance test indicated blood glucose at 120 minutes was higher in the olanzapine alone-treated group than in groups treated with vehicle and olanzapine + Tat-3L4F (10 µmol kg-1 per day). Furthermore, compared with olanzapine alone treatment, treatment with Tat-3L4F (10 µmol kg-1 per day) significantly inhibited PTEN expression in the hypothalamus. The olanzapine alone-treated group had the highest bile acid level, followed by the olanzapine with Tat-3L4F (1 µmol kg-1) group, olanzapine with Tat-3L4F (10 µmol kg-1) group, and vehicle group. CONCLUSIONS: Our present results reveal that Tat-3L4F is a potential pharmacological strategy for suppressing hyperphagia and weight gain induced by olanzapine, which acts through disrupting crosstalk between HTR2C and PTEN as a result of PTEN downregulation in the hypothalamus.

Sonographic Features and Diagnosis of Peripheral Schwannomas.

BACKGROUND: To determine the sonographic features of peripheral schwannomas. METHODS: This retrospective study included 54 cases of schwannoma in 51 patients. Ultrasonography (US) and MRI were performed in all patients. The US features of each tumor were analyzed and compared with pathologic findings. The US target sign was compared with the MRI findings. RESULTS: On US, 53 of the 54 schwannomas had a regular shape and clear margins, and one had an irregular shape. Thirty-seven of the 54 schwannomas were categorized as solid, 16 as cystic and solid, and one as entirely cystic; distal sound enhancement was associated with 47 schwannomas. The target sign was seen in 24, the rat tail sign in 28, the vessel accompanying sign in 22, and the split fat sign in 5. The entering and exiting nerves were situated centrally in 9 and eccentrically in 19 schwannomas. Vascularity on color Doppler imaging using a 0 to III scale was graded 0 in 4 schwannomas, I in 10, II in 26, and III in 14. Twenty-four target signs were detected in 54 schwannomas by US, and 28 were detected by MRI. There was good agreement between the target signs noted on US and those seen on MRI (κ = 0.631, p < 0.001). CONCLUSIONS: The sonographic diagnosis of peripheral schwannomas is feasible and reliable. The target sign is a prominent US feature in peripheral schwannomas, comparable to that observed with MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:127-133, 2017.

The effects of lanthanum chloride on proliferation and apoptosis of cervical cancer cells: involvement of let-7a and miR-34a microRNAs.

Lanthanide elements have been documented to possess various biologic effects, and their compounds have been studied intensely for their anti-cancer potential. However, the underlying mechanisms remain largely unknown. In the present study, we propose that the levels of proliferation and apoptosis related microRNAs (miRNAs), let-7a and miR-34a, which mediate the apoptosis of cervical cancer cells, can be affected by the lanthanum ion. Our data showed that LaCl3 inhibited the proliferation and induced the apoptosis of cervical cancer cells both in vivo and in vitro by regulating let-7a, miR-34a and their downstream genes. This study provides novel evidence demonstrating that the anticancer mechanism of lanthanum chloride is partially attributed to miRNAs regulation and establishes an experimental basis for the clinical application of lanthanum chloride as an anti-cancer drug.

The effects of childhood trauma on nonsuicidal self-injury and depressive severity among adolescents with major depressive disorder: The different mediating roles of positive and negative coping styles.

OBJECTIVE: We aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD). METHODS: The Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD. RESULTS: MDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (ß = 0.075, 95 % CI: 0.042-0.107) and ineffectiveness (ß = -0.084, 95 % CI: -0.160 âˆ¼ -0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (ß = 0.884, 95 % CI: 0.570-1.197), sexual abuse (ß = 0.825, 95 % CI: 0.527-1.124) and negative coping style (ß = 0.370, 95 % CI: 0.036-0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001-0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005-0.051) in adolescents with MDD. LIMITATIONS: A cross-sectional design, the retrospective self-reported data, the small sample size. CONCLUSION: Our findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents.

Aberrant patterns of spontaneous brain activity in schizophrenia: A resting-state fMRI study and classification analysis.

BACKGROUND: Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was conducted to explore the aberrant spontaneous brain activity and investigate the potential of abnormal brain indices as diagnostic biomarkers employing machine learning methods. METHODS: A total of sixty-one schizophrenia patients and seventy demographically matched healthy controls were enrolled in this study. The static indices of resting-state functional magnetic resonance imaging (rs-fMRI) including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated to evaluate spontaneous brain activity. Subsequently, a sliding-window method was then used to conduct temporal dynamic analysis. The comparison of static and dynamic rs-fMRI indices between the patient and control groups was conducted using a two-sample t-test. Finally, the machine learning analysis was applied to estimate the diagnostic value of abnormal indices of brain activity. RESULTS: Schizophrenia patients exhibited a significant increase ALFF value in inferior frontal gyrus, alongside significant decreases in fALFF values observed in left postcentral gyrus and right cerebellum posterior lobe. Pervasive aberrations in ReHo indices were observed among schizophrenia patients, particularly in frontal lobe and cerebellum. A noteworthy reduction in voxel-wise concordance of dynamic indices was observed across gray matter regions encompassing the bilateral frontal, parietal, occipital, temporal, and insular cortices. The classification analysis achieved the highest values for area under curve at 0.87 and accuracy at 81.28% when applying linear support vector machine and leveraging a combination of abnormal static and dynamic indices in the specified brain regions as features. CONCLUSIONS: The static and dynamic indices of brain activity exhibited as potential neuroimaging biomarkers for the diagnosis of schizophrenia.

Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder.

BACKGROUND: Anhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. METHODS: This study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. RESULTS: Demographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. CONCLUSION: These findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia. Clinicl Trial Registration Number: NCT03790085.

Comparison of brain network between schizophrenia and bipolar disorder: A multimodal MRI analysis of comparative studies.

OBJECTIVE: Cognitive impairment is a shared symptom of Schizophrenia (SCZ) and bipolar disorder (BP), but the underlying neural mechanisms for both remain unclear. We aimed to identify abnormalities in the structural and functional brain network of patients with SCZ and BP. METHODS: The study included 69 patients with SCZ, 40 with BP, and 63 healthy controls (HC). After neurocognitive function assessment, resting-state functional magnetic resonance imaging and diffusion tensor imaging were acquired respectively. We compared the network of structural connectivity (SC) and functional connectivity (FC) among the three groups and performed graph theoretical analyses. The SC-FC coupling was calculated, and the correlations between the cognitive function scores and network properties were ascertained. RESULTS: The BP group showed significantly higher indicators in subnetworks and graph theory analysis than SCZ and HC. Several brain regions, such as the inferior parietal lobe, exhibited differences among all pairwise comparisons and showed significant correlations with cognitive scores in both SCZ and BP. SC-FC coupling did not significantly differ between the three groups but showed close associations with clinical performance. Interestingly, the direction of correlations between the network properties and cognition tends to present the opposite between SCZ and BP, especially regarding the working memory, attention, and language sections. CONCLUSIONS: The FC and SC network of the SCZ group appeared more inefficient and disconnected than BP. The network demonstrated to be closely but differently associated with cognitive function at both local and global levels, indicating the potentially separated pathologies of cognition deficits in SCZ and BP.

Increased cortical structural covariance correlates with anhedonia in schizophrenia.

Anhedonia is a common symptom in schizophrenia and is closely related to poor functional outcomes. Several lines of evidence reveal that the orbitofrontal cortex plays an important role in anhedonia. In the present study, we aimed to investigate abnormalities in structural covariance within the orbitofrontal subregions, and to further study their role in anticipatory and consummatory anhedonia in schizophrenia. T1 images of 35 schizophrenia patients and 45 healthy controls were obtained. The cortical thickness of 68 cerebral regions parcellated by the Desikan-Killiany (DK) atlas was calculated. The structural covariance within the orbitofrontal subregions was calculated in both schizophrenia and healthy control groups. Stepwise linear regression was performed to examine the relationship between structural covariance and anhedonia in schizophrenia patients. Patients with schizophrenia exhibited higher structural covariance between the left and right medial orbitofrontal thickness, the left lateral orbitofrontal thickness and left pars orbitalis thickness compared to healthy controls (p < 0.05, FDR corrected). This results imply that the increased structural covariance in orbitofrontal thickness may be involved in the process of developing anhedonia in schizophrenia. The result indicated that the increased structural covariance between the left and right medial orbitofrontal thickness might be a protective factor for anticipatory pleasure (B' = 0.420, p = 0.012).

Correlation of Orexin-A and brain-derived neurotrophic factor levels in metabolic syndrome and cognitive impairment in schizophrenia treated with clozapine.

Orexin-A and brain-derived neurotrophic factor (BDNF) are implicated in regulating metabolic syndrome (MetS) and cognitive impairment of schizophrenia. However, the associations among them remains unclear. Here, we aimed to investigate the relationship between Orexin-A levels, BDNF, MetS, clinical symptom profile, and cognitive function in schizophrenia patients following long-term clozapine treatment. We measured Orexin-A and BDNF levels in 140 schizophrenia patients with and without MetS. We assessed clinical symptoms on the Positive and Negative Syndrome Scale and cognitive function by the assessment of Neuropsychological Status (RBANS), and examined their associations with Orexin-A. Patients with MetS had significantly lower Orexin-A levels and higher coding test, attention span and delayed retention in RBANS (P < 0.05). Correlation analysis showed that Orexin-A was associated with BDNF, TG, HDLC, PANSS active social avoidance and emotional withdrawal significantly. Besides, Orexin-A significantly interacted with BDNF for metabolic and cognitive profiles including waist circumference, delayed retention and list recognition. Logistic regression analysis showed that Orexin-A level (odds ratio [OR] = 0.380, 95% confidence interval [CI]: 0.151-0.952, P = 0.039) and total illness duration (OR = 0.932, 95% CI: 0.875-0.991, P = 0.025) were predictive variables of MetS. However, there was no significant relationship between Orexin-A and cognitive function after adjustment for age, sex and educational levels. Totally, a lower plasma Orexin-A level seems to be related to metabolic parameters more than cognitive profiles. The interaction of Orexin-A with BDNF may be partly responsible for worse MetS and better cognition of elderly schizophrenia, but the causal relationship needs further clarification.

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia.

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1ß, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1ß, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1ß, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Abnormal functional connectivity of the anterior cingulate cortex subregions mediates the association between anhedonia and sleep quality in major depressive disorder.

BACKGROUND: The anterior cingulate cortex (ACC) is a crucial region in the pathophysiology of major depressive disorder (MDD). However, the relationship between functional alterations of the ACC subregions, anhedonia and sleep quality remains unclear in MDD patients. METHODS: The resting-state functional connectivity (rsFC) of ACC subregions was measured in 41 first-episode medication-naïve MDD patients and 63 healthy controls who underwent functional magnetic resonance imaging. Between-group differences were examined using two-sample t-test. Furthermore, correlation and mediation analyses were carried out to investigate the relationships between the aberrant rsFC of ACC subregions, anhedonia and sleep quality in the patients and controls. RESULTS: Compared to healthy controls, the MDD patients exhibited increased rsFC of ACC subregions to areas of the anterior default mode network (DMN) and showed decreased rsFC of the right subgenual ACC to left precuneus (PCUN), which belongs to the posterior DMN. In MDD group, the sleep quality and consummatory anhedonia are correlated with some rsFC, which involves the angular gyrus (ANG) and superior frontal gyrus (SFG). More importantly, the rsFC between the right perigenual ACC and left SPG mediates the association between anhedonia and sleep quality in MDD. LIMITATIONS: The cross-sectional design and the subjective questionaries for assessment. CONCLUSION: These findings confirm the functional alterations of the ACC subregions and reveal the mediating role of ACC subregions in sleep and reward dysfunction in MDD.

Altered brain activity in the bilateral frontal cortices and neural correlation with cognitive impairment in schizophrenia.

Cognitive impairments are core aspects of schizophrenia and are highly related to poor outcomes. However, the effect of therapy on cognitive impairments remains unsatisfactory as its biological mechanisms are not fully understood. The purpose of this study was to investigate the disrupted intrinsic neural activity of the frontal areas and to further examine the functional connectivity of frontal areas related to cognitive impairments in schizophrenia. We collected brain imaging data using a 3T Siemens Prisma MRI system in 32 patients with schizophrenia and 34 age- and sex-matched healthy controls. The mean fractional amplitude of low-frequency fluctuation (mfALFF) in the frontal regions was calculated and analyzed to evaluate regional neural activity alterations in schizophrenia. Seed regions were generated from clusters showing significant changes in mfALFF in schizophrenia, and its resting-state functional connectivity (rs-FC) with other brain regions were estimated to detect possible aberrant rs-FC indicating cognitive impairments in schizophrenia. We found that mfALFF in the bilateral frontal cortices was increased in schizophrenia. mfALFF-based rs-FC revealed that decreased rs-FC between left middle frontal gyrus (MFG) and left medial superior frontal gyrus (MFSG) was associated with poor delayed memory (r = 0.566, Bonferroni-corrected p = 0.012). These findings demonstrate increased neural activity in the frontal cortices in schizophrenia. FC analysis revealed a diminished rs-FC pattern between the left MFG and left MSFG that was associated with cognitive impairments. These findings have provided deeper insight into the alterations in brain function related to specific domains of cognitive impairment and may provide evidence for precise interventions for cognitive deficits in schizophrenia.

Deficits in multi-scale top-down processes distorting auditory perception in schizophrenia.

Cognitive models postulate that impaired source monitoring incorrectly weights the top-down prediction and bottom-up sensory processes and causes hallucinations. However, the underlying mechanisms of the interaction, such as whether the incorrectly weighting is ubiquitously on all levels of sensory features and whether different top-down processes have distinct effects in subgroups of schizophrenia are still unclear. This study investigates how multi-scale predictions influence perception of basic tonal features in schizophrenia. Sixty-three schizophrenia patients with and without symptoms of auditory verbal hallucinations (AVHs), and thirty healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences (long-term regularity) or a repetition between the target tone and the tone immediately before (short-term repetition). The sensitivity index, d prime (d'), was obtained to assess the modulation of predictions on tone identification. Patients with AVHs showed higher d' when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than when the target tones were inconsistent with the pattern. Whereas, the short-term repetition modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. Our results suggest that impaired source monitoring in schizophrenia patients with AVHs heavily weights top-down predictions over bottom-up perceptual processes to form incorrect perception. The weighting function in source monitoring can extend to the processes of basic tonal features, and predictions at multiple timescales could differentially modulate perception in different clinical populations. The impaired interaction between top-down and bottom-up processes might underlie the development of hallucination symptoms in schizophrenia.

Association of Cognitive Impairment With Anhedonia in Patients With Schizophrenia.

Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all P > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all P < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all P < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia (B' = 0.265, P = 0.008, 95% CI: 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia (B' = 0.391, P < 0.001, 95% CI:0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.

A novel risk model to predict first-ever ischemic stroke in heart failure with reduced ejection fraction.

Patients with heart failure are at increased risk for ischemic stroke. We aim to develop a more accurate stroke risk prediction tools identify high-risk patients with heart failure with reduced ejection fraction (HFrEF). Patient data were extracted retrospectively from the electronic medical database between January 2009 and February 2019. Univariate and multivariate Cox regression analysis were performed to identify independent predictors, which were utilized to construct a nomogram for predicting ischemic stroke. AUROC analysis was used to compare the prognostic value between the new risk score and CHADS2/CHA2DS2-VASc scores. In 6087 patients with HFrEF, the risk of first-ever ischemic stroke was 5.8% events/pts-years (n=468) during 8007.2 person-years follow-up. A nomogram constructed by integrating 6 variables, including age, atrial fibrillation (AF), deep vein thrombosis (DVT), d-dimer, anticoagulant use and spontaneous echocardiographic contrast (SEC)/left ventricular thrombus (LVT), exhibited a greater area under the curve of 0.727, 0.728 and 0.714 than that by CHADS2 score (0.515, 0.522 and 0.540), and by CHA2DS2-VASc score (0.547, 0.553 and 0.562) for predicting first-ever ischemic stroke at hospitalization, 30-day and 6-month follow-up (all p<0.001). This novel stroke risk score performed better than existing CHADS2/ CHA2DS2-VASc scores and showed improvement in predicting first-ever ischemic stroke in HFrEF patients.