Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia.

BACKGROUND: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). METHODS: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). RESULTS: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. CONCLUSIONS: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study.

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. RESULTS: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]). CONCLUSION: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Immunosenescence-related T cell phenotypes and white matter in schizophrenia patients with tardive dyskinesia.

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD.

Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders.

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD). Methods: Patients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication. Results: The levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms. Conclusions: Patients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms.

Correlation of allostatic load and perceived stress with clinical features in first-episode schizophrenia.

BACKGROUND: Stress plays an important role in the etiology of schizophrenia. However, the mechanisms by which chronic physiological stress and perceived stress relate to the clinical features of schizophrenia may differ. We aimed to elucidate the relationships among chronic physiological stress indexed by allostatic load (AL), perceived stress, and clinical symptoms in individuals with first-episode schizophrenia (FES). METHODS: Individuals with FES (n = 90, mean age = 28.26years old, 49%female) and healthy controls (111, 28.88, 51%) were recruited. We collected data of 13 biological indicators to calculate the AL index, assessed subjective stress with the Perceived Stress Scale-14 (PSS-14), and compared AL and perceived stress between groups. Patients with FES were also evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: Individuals with FES had higher AL and PSS score than healthy controls. There were no significant correlations between AL and PSS score in either patients or controls. Among individuals with FES, the AL index was associated with the severity of positive symptoms, while the PSS score was positively associated with CDSS score. Both elevated AL and PSS were correlated with the occurrence of schizophrenia. CONCLUSIONS: Physiological stress, as reflected by AL, may be more related to positive symptoms, while perceived stress appear to be associated with depressive symptoms in individuals with FES. Longitudinal studies are necessary to explore the relationships between interventions for different stressor types and specific clinical outcomes in FES.

Immune-Inflammatory Response And Compensatory Immune-Regulatory Reflex Systems And White Matter Integrity in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia. STUDY DESIGN: Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ±â€…13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ±â€…12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio. STUDY RESULTS: The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P = .009). SCZ had a significantly lower whole-brain white matter average FA (P < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r = 0.29, P = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r = -0.23, P = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P = .217) in SCZ. CONCLUSIONS: Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC.

Cortical thickness of the inferior parietal lobule as a potential predictor of relapse in men with alcohol dependence.

Alcohol dependence is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with alcohol dependence. This study enrolled 58 male patients with alcohol dependence who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at six months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobules were significantly higher in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse, and lower non-planning impulse was a protective factor against relapse. Relapsers show poorer impulse control than abstainers, and structural magnetic resonance imaging revealed a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with alcohol dependence.

Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia.

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imbalance in the pathophysiological mechanism of schizophrenia. This study aimed to explore the little-known area regarding the composite score of peripheral cytokines, the IRS/CIRS, and its correlation with white matter integrity and the specific microstructures most affected in schizophrenia. First-episode patients with schizophrenia (FEPS, n = 94) and age- and sex-matched healthy controls (HCs, n = 50) were enrolled in this study. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The whole brain white matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging (DTI) using a 3-T Prisma MRI scanner. The IRS/CIRS in FEPS was significantly higher than that in HCs (p = 1.5 × 10-5) and Cohen's d effect size was d = 0.74. FEPS had a significantly lower whole-brain white matter average FA (p = 0.032), which was negatively associated with IRS/CIRS (p = 0.029, adjusting for age, sex, years of education, BMI, and total intracranial volume), but not in the HCs (p > 0.05). Among the white matter microstructures, only the cortico-spinal tract was significantly correlated with IRS/CIRS in FEPS (r = - 0.543, p = 0.0009). Therefore, elevated IRS/CIRS may affect the white matter in FEPS.

Regional Homogeneity in schizophrenia patients with tardive dyskinesia: a resting-state fMRI study.

Neuronal degeneration and apoptosis may play an important role in the pathogenesis of tardive dyskinesia (TD). Previous studies suggested brain structural and functional abnormalities in patients with TD. We investigated changes in cerebral regional homogeneity (ReHo) in patients with TD using resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were collected from schizophrenia patients with TD (TD group, n=58) and without TD (non-TD group, n=66) and healthy controls (HC group, n=67), processed with SPM, and evaluated at a corrected threshold. Psychopathology and severity of TD were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Results: TD vs. non-TD group showed significantly higher ReHo in the Left Inferior Semilunar Lobule and Right Fusiform Gyrus and lower ReHo in Left Supramarginal Gyrus, Right Inferior Tempotal Gyrus, and Left Medial Frontal Gyrus. The ReHo value in the Left Inferior Semilunar Lobule was negatively correlated with AIMS upper limbs scores. Conclusions: The findings suggest altered regional neural connectivities in association with TD and may inform research of the etiology and monitor the course of TD in patients with schizophrenia and potentially other psychotic disorders.

CSF1R regulates schizophrenia-related stress response and vascular association of microglia/macrophages.

BACKGROUND: Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility. METHODS: We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology. RESULTS: FES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31+-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05). CONCLUSION: Microglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis.

Changes in Inflammatory Biomarkers in Patients with Schizophrenia: A 3-Year Retrospective Study.

Objective: Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflammatory state in patients with schizophrenia by using these indicators. Methods: In this study, the complete blood count data for 187 continuing hospitalized patients with schizophrenia and 187 age- and sex-matched healthy participants was collected annually from 2017 to 2019. Platelet (PLT), lymphocyte (LYM), monocyte (MON) and neutrophil (NEU) counts were aggregated and NLR, MLR, PLR, and SII were calculated. Using a generalized linear mixed model, we assessed the impact of age, sex, diagnosis, and sampling year on the above indicators and evaluated the interaction between the factors. Results: According to the estimation results of the generalized linear mixed model, the NLR increased by 0.319 (p = 0.004), the MLR increased by 0.037 (p < 0.001), and the SII increased by 57.858 (p = 0.018) in patients with schizophrenia. Data after two years of continuous antipsychotic treatment showed that the NLR and MLR were higher in patients with schizophrenia than those in healthy controls, while the PLT and LYM counts were decreased in patients with schizophrenia. The schizophrenia diagnosis was correlated to the MON and LYM count, NLR, MLR, and SII (p < 0.05). Conclusion: The differences in these markers were stable and cannot be eliminated by a full course of treatment. This study provides impetus for the inflammatory hypothesis of schizophrenia.

Short-term antipsychotic treatment response in early-onset, typical-onset, and late-onset first episode schizophrenia.

In schizophrenia, the age at illness onset may reflect genetic loading and predict prognosis. We aimed to compare the pre-treatment symptom profiles and clinical symptom responses to antipsychotic treatment of individuals with late-onset schizophrenia (LOS; onset age: 40-59 years) with individuals with early-onset schizophrenia (EOS; onset age < 18 years) or typical-onset schizophrenia (TOS; onset age: 18-39 years). We conducted an 8-week cohort study in inpatient departments of five mental health hospitals in five cities in China. We included 106 individuals with LOS, 80 with EOS, and 214 with TOS. Their onset of schizophrenia was within three years and the disorders were minimally treated. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at baseline and after 8 weeks of antipsychotic treatment. Mixed effect models were used to compare symptom improvement within eight weeks. Antipsychotic therapy reduced all PANSS factor scores in all three groups. LOS had significantly better improvement in PANSS positive factor scores than EOS at week 8 after adjusting for sex, duration of illness, dose equivalents of antipsychotics at baseline, sites as fixed effects, and individuals as random effects. LOS was associated with reduced positive factor scores at week 8 when receiving 1 mg olanzapine dose equivalent per 1 kg body weight compared with EOS or TOS. In conclusion, LOS had better early improvement of positive symptoms than EOS and TOS. Thus, personalized treatment for schizophrenia should consider the age of onset.

A Modified Unilateral Extrapedicular Approach Applied to Percutaneous Kyphoplasty to Treat Lumbar Osteoporotic Vertebral Compression Fracture: A Retrospective Analysis.

BACKGROUND: In recent years, many extrapedicular puncture methods have been applied to percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs). However, these techniques were generally complex and had the risk of some puncture-related complications, which greatly limited the wide applications in PKP. Finding a safer and more feasible extrapedicular puncture method was rather important. OBJECTIVES: To evaluate the treatment effect of modified unilateral extrapedicular PKP in patients with lumbar OVCFs clinically and radiologically. STUDY DESIGN: Retrospective study. SETTING: Department of Orthopedic Surgery, an affiliated hospital of a medical university. METHODS: Patients who were treated by modified unilateral extrapedicular PKP in our institution, from January 2020 to March 2021, were retrospectively enrolled. The degree of pain relief and functional recovery were evaluated by the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI), respectively. Radiologic results were assessed including anterior vertebral height (AVH) and kyphotic angle. In addition, volumetric analysis was performed to evaluate bone cement distribution. And the intraoperative data and complications were also recorded. RESULTS: A total of 48 patients with lumbar OVCFs were successfully treated by modified unilateral extrapedicular PKP. All patients experienced a significant decrease in VAS and ODI scores after surgery (P < 0.01) and maintained the statistical significance until the last follow-up (P < 0.01), as well as significant AVH restoration (P < 0.01) and kyphotic angle correction (P < 0.01) compared with preoperative corresponding values. Volumetric analysis showed that all cases of bone cement diffused across the midline of the vertebral body (VB), in which 43 patients (89.6%) presented optimal contralateral distribution with good or excellent bone cement spread. In addition, 8 patients (16.7%) experienced asymptomatic cement leakage, and no other severe complications, such as injuries to segmental lumbar arteries and nerve roots, were found. LIMITATIONS: A noncontrol study with a small patient population and short follow-up duration. CONCLUSIONS: Modified unilateral extrapedicular PKP, in which the puncture trajectory was advanced through the bottom of Kambin's triangle to or across the midline of VB for proper bilateral cement distribution, greatly alleviated back pain and restored the morphology of fractured vertebrae. It seemed to be a safe and effective alternative applied to treat lumbar OVCFs with appropriate patient selection.

Inflammatory disequilibrium and lateral ventricular enlargement in treatment-resistant schizophrenia.

Treatment-resistant schizophrenia (TRS) patient respond poorly to antipsychotics. Inflammatory imbalance involving pro- and anti-inflammatory cytokines may play an important role in the mechanism of antipsychotic-medication response. This study aimed to investigate immune imbalance and how the latter relates to clinical manifestations in patients with TRS. The level of net inflammation was estimated by evaluating the immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) in 52 patients with TRS, 47 with non-TRS, and 56 sex and age matched healthy controls. The immune biomarkers mainly included macrophagic M1, T helper, Th-1, Th-2, Th-17, and T regulatory cytokines and receptors. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Subcortical volumes were quantified using a 3-T Prisma Magnetic Resonance Imaging scanner. The results showed that (1) patients with TRS were characterized by activated pro-inflammatory cytokines and relatively insufficient anti-inflammatory cytokines, with an elevated IRS/CIRS ratio indicating a new homeostatic immune setpoint; (2) IRS/CIRS ratio was positively correlated with larger lateral ventricle volume and higher PANSS score in patients with TRS. Our findings highlighted the inflammatory disequilibrium as a potential pathophysiological process of TRS.

Cortical thickness of the inferior parietal lobule as a potential predictor of relapse in men with alcohol dependence.

Background: Alcohol dependence (AD) is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with AD. Methods: This study enrolled 58 male patients with AD who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging (MRI) data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at 6 months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Results: Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobule were significantly greater in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse. Conclusions: Relapsers show poorer impulse control than abstainers, and MRI imaging shows a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with AD.

History of suicide attempt associated with amygdala and hippocampus changes among individuals with schizophrenia.

Abnormalities in subcortical brain structures may reflect higher suicide risk in mood disorders, but less is known about its associations for schizophrenia. This cross-sectional imaging study aimed to explore whether the history of suicide attempts was associated with subcortical changes among individuals with schizophrenia. We recruited 44 individuals with schizophrenia and a history of suicide attempts (SZ-SA) and 44 individuals with schizophrenia but without a history of suicide attempts (SZ-NSA) and 44 healthy controls. Linear regression showed that SZ-SA had smaller volumes of the hippocampus (Cohen's d = -0.72), the amygdala (Cohen's d = -0.69), and some nuclei of the amygdala (Cohen's d, -0.57 to -0.72) than SZ-NSA after adjusting for age, sex, illness phase, and intracranial volume. There was no difference in the volume of the subfields of the hippocampus. It suggests the history of suicide attempts is associated with subcortical volume alterations in schizophrenia.

The age of onset and cognitive impairment at the early stage of schizophrenia.

In schizophrenia, the age of first episode onset can reflect genetic loading and predict prognosis. Little is known about the association between the age of onset and cognition among individuals with early-stage schizophrenia. We aimed to compare the pre-treatment neurocognition profile between individuals with early-onset schizophrenia (EOS, the age of onset < 18 years), typical-onset schizophrenia (TOS, the age of onset between 18 and 39 years), and late-onset schizophrenia (LOS, the age of onset between 40 and 59 years). We included individuals with a current diagnosis of schizophrenia within 3 years and medication naive or less than 2 weeks of cumulative antipsychotic exposure and current daily antipsychotic dosage equivalent to ≤ 15 mg of olanzapine. Assessments included the MATRICS Consensus Cognitive Battery (MCCB) and the Positive and Negative Syndrome Scale (PANSS). We used linear regression to compare the difference between age-of-onset groups. We included 356 participants (67 EOS, 195 TOS, and 94 LOS). Compared with LOS, TOS was associated with lower scores in the verbal learning scores of the MCCB after adjusting for education years and the subscale scores of the PANSS (45.5 ± 12.9 vs. 40.5 ± 14.1, adjusted B = - 5.79, p = 0.001). The three groups had no difference in other cognitive domain scores. The association between the age of onset and MCCB verbal memory was U-shape (square of the age of onset, adjusted B = 0.02, p = 0.003). Patients with LOS had a better verbal learning function compared with individuals with TOS. These findings suggest that involvement of cognition assessment and rehabilitation training is necessary for patients with TOS.

Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway.

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

Auditory Hallucinations, Depressive Symptoms, and Current Suicidal Ideation or Behavior Among Patients with Acute-episode Schizophrenia.

Suicide risk and auditory hallucinations are common in schizophrenia, but less is known about its associations. This cross-sectional study aimed to determine whether the presence and severity of auditory hallucinations were associated with current suicidal ideation or behavior (CSIB) among patients with schizophrenia. We interviewed 299 individuals with schizophrenia and acute symptoms and reviewed their medical records. Measurement included the Psychotic Symptom Rating Scale (PSYRATS-AH), the Calgary Depression Scale for Schizophrenia (CDSS), and the Positive and Negative Syndrome Scale. Logistic regression and path analysis were used. The CSIB prevalence was higher among patients with current auditory hallucination than those without (19.5% vs. 8.6%, crude odds ratio = 2.58, p = .009). Lifetime auditory hallucination experience (adjusted odds ratio [AOR] = 3.81; 95% CI: 1.45-10.05) or current auditory hallucination experience (AOR = 3.22; 95% CI: 1.25-8.28) can elevate the likelihood of CSIB while controlling for depressive symptoms and lifetime suicide-attempt history. Among those with auditory hallucinations, the emotional score of the PSYRATS-AH was positively associated with the CDSS score and there was a small indirect effect of the CDSS score on the association between the emotional domain score and CSIB (bias-corrected 95% CI, 0.02-0.20). In conclusion, the presence of auditory hallucinations was strongly associated with CSIB, independent of depressive symptoms and lifetime suicide attempts. Suicide risk assessment should consider auditory hallucination experience and patients' appraisal of its emotional characteristics. Future cohort studies are necessary to provide more conclusive evidence for the mediating pathways between auditory hallucinations and CSIB.HIGHLIGHTSThe presence of auditory hallucinations was associated with current suicidality.Auditory hallucinations' emotional severity was related to depressive symptoms.The severity of auditory hallucination was not directly associated with suicidality.

Association of cortical thickness and cognition with schizophrenia treatment resistance.

AIM: Approximately a third of patients with schizophrenia fail to adequately respond to antipsychotic medications, a condition known as treatment resistance (TR). We aimed to assess cognitive and cortical thickness deficits and their relationship to TR in schizophrenia. METHOD: We recruited patients with schizophrenia (n = 127), including patients at treatment initiation (n = 45), treatment-responsive patients (n = 40) and TR patients (n = 42), and healthy controls (n = 83). Clinical symptoms, neurocognitive function, and structural images were assessed. We performed group comparisons, and explored association of cortical thickness and cognition with TR. RESULTS: The TR patients showed significantly more severe clinical symptoms and cognitive impairment relative to the treatment-responsive group. Compared to healthy controls, 56 of 68 brain regions showed significantly reduced cortical thickness in patients with schizophrenia. Reductions in five regions were significantly associated with TR (reduction in TR relative to treatment-responsive patients), i.e. in the right caudal middle frontal gyrus, superior frontal cortex, fusiform gyrus, pars opercularis of the inferior frontal cortex, and supramarginal cortex. Cognition deficits were also significantly correlated with cortical thickness in these five regions in patients with schizophrenia. Cortical thickness of the right caudal middle frontal gyrus, superior frontal cortex and pars opercularis of the inferior frontal cortex also significantly mediated effects of cognitive deficits on TR. CONCLUSION: Treatment resistance in schizophrenia was associated with reduced thickness in the right caudal middle frontal gyrus, superior frontal cortex, fusiform gyrus, pars opercularis of the inferior frontal cortex, and supramarginal cortex. Cortical abnormalities further mediate cognitive deficits known to be associated with TR.