N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. STUDY DESIGN: We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. STUDY RESULTS: The FES group showed higher serum NMDAR Ab levels [(9.23 ±â€…4.15) ng/mL vs. (7.08 ±â€…2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). CONCLUSIONS: Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

Suicidality, perceived chronic stress, and stress-induced cortisol changes of individuals with schizophrenia.

The associations of suicidality with stress are poorly studied in schizophrenia. The study aimed to determine whether suicidality was correlated with perceived chronic stress and the cortisol fluctuations under stress tasks in schizophrenia. High suicidality was defined as a lifetime history of suicide attempts or suicidal ideation in the past 2 weeks. Individuals with schizophrenia and high suicidality (SZ-HS, n = 59), with low suicidality (SZ-LS, n = 207), and healthy controls (HC, n = 196) finished the Perceived Stress Scale. Then, they participated in an experiment that induced stress using the Paced Auditory Serial Addition Task and the Mirror Tracing Persistence Task. Negative affect was measured at baseline and after finishing each task. The salivary cortisol was collected before-, after 20 min, and after 40 min of the tasks. SZ-HS had elevated perceived stress than SZ-LS and HC. Mixed effect models showed that stress tasks induced cortisol changes in all groups; cortisol of SZ-LS was reduced more than HC, but SZ-HS and SZ-LS did not differ in cortisol fluctuations. SZ-HS and SZ-LS experienced similar negative affect changes during tasks and the difference in withdrawal rates was nonsignificant. SZ-HS had an increased error rate than SZ-LS. In conclusion, suicidality was correlated with high-level perceived stress but did not result in differences in cortisol reactivities under stress tasks. It suggests the inconsistency between appraisal of stress and biological stress system disturbance among SZ-HS compared to SZ-LS.

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.

Construction of N-Aryl-Substituted Pyrrolidines by Successive Reductive Amination of Diketones via Transfer Hydrogenation.

N-aryl-substituted pyrrolidines are important moieties widely found in bioactive substances and drugs. Herein, we present a practical reductive amination of diketones with anilines for the synthesis of N-aryl-substituted pyrrolidines in good to excellent yields. In this process, the N-aryl-substituted pyrrolidines were furnished via successive reductive amination of diketones via iridium-catalyzed transfer hydrogenation. The scale-up performance, water as a solvent, simple operation, as well as derivation of drug molecules showcased the potential application in organic synthesis.

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.

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.

Role of the immune-kynurenine pathway in treatment-resistant schizophrenia.

BACKGROUND: The immune-inflammatory response system (IRS) and kynurenine pathway (KP) have been implicated in the pathophysiology of schizophrenia. Studies have shown inflammation-related effects on KP metabolism in patients with schizophrenia. This study investigated the relationship between KP metabolites, IRS, and the compensatory immune-regulatory reflex system (CIRS) in patients with treatment-resistant schizophrenia (TRS). METHODS: Patients with (n = 53) and without TRS (n = 47), and healthy controls (HCs, n = 49) were enrolled. We quantified plasma levels of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-6, soluble(s)IL-6 receptor, IL-8, IL-12, IL-17, IL-18, interferon-γ, and tumor necrosis factor[TNF]-α) and anti-inflammatory cytokines (IL-1 receptor antagonist, IL-4, IL-10, tumor growth factor [TGF]-ß1, TGF-ß2, soluble (s) IL-2 receptor subunit α, sIL-2 receptor subunit ß, and sTNF-α receptor 1) and calculated the IRS/CIRS ratio. We also tested serum metabolites of the KP, including kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN), along with the QUIN/KYNA ratio. RESULTS: Patients with TRS had significantly higher IRS/CIRS ratio than non-TRS patients (p = 0.002) and HCs (p = 0.007), and significantly lower KYN (p = 0.001) and KYNA (p = 0.01) levels than HCs. Binary logistic regression analysis revealed that a younger age at illness onset (odds ratio [OR] = 0.91, p = 0.02) and a higher IRS/CIRS ratio (OR = 1.22; p = 0.007) were risk factors for patients with TRS. After further adjusted for age of onset, the QUIN/KYNA ratio (ß = 0.97; p = 0.02) significantly moderated the relationship between IRS/CIRS and TRS, showing that in the higher QUIN/KYNA condition, higher IRS/CIRS ratio were significantly and more likely to be associated with patients with TRS (ß = 0.12, z = 3.19, p = 0.001), whereas in the low QUIN/KYNA condition, the association between IRS/CIRS ratio and TRS was weak and insignificant. CONCLUSIONS: The peripheral immune response was imbalanced in TRS and was preferentially directed towards the IRS compared to patients without TRS and healthy controls, which is likely to play a role in neurotoxicity. Additionally, peripheral KP activation was also imbalanced, as evidenced by significantly reduced KYN and KYNA levels in patients with TRS compared to healthy controls, but none of KP metabolisms were significantly difference in non-TRS patients compared to healthy controls. QUIN/KYNA ratio involving to the degree of activation of NMDA receptors, indicated the neurotoxic level of the KP activation. The interaction between IRS/CIRS and QUIN/KYNA ratio was significant in predicting TRS, and our findings suggest a potential role for the immune-kynurenine pathway in TRS pathogenesis.

Iridium-catalysed reductive allylic amination of α,ß-unsaturated aldehydes.

Allylic amination is a powerful tool for constructing N-allylic amines widely found in bioactive molecules. Generally, allylic alcohols and unsaturated hydrocarbons have been considered for allylic amination reactions to minimize waste production. Herein, we present an iridium-catalysed method for reductive allylic amination of α,ß-unsaturated aldehydes with amines to afford N-allylic amines under air conditions. This protocol is demonstrated to provide products from many substrates (41 examples) in moderate-to-excellent yields. This synthetic methodology is also highlighted by the synthesis of drug molecules, optically pure products, as well as scale-up experiments.

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.

One-pot reductive amination of carbonyl compounds and nitro compounds via Ir-catalyzed transfer hydrogenation.

The formation of C-N bond is a vital synthetic tool for establishing molecular diversity, which is highly sought after in a wide range of biologically active natural products and drugs. Herein, we present a new strategy for the synthesis of secondary amines via iridium-catalyzed one-pot reductive amination of carbonyl compounds with nitro compounds. This method is demonstrated for a variety of carbonyl compounds, including miscellaneous aldehydes and ketones, which are compatible with this catalytic system, and deliver the desired products in good yields under mild conditions. In this protocol, the reduction of nitro compounds occurs in situ first, followed by reductive amination to form amine products, providing a new one-pot procedure for amine synthesis.

Collaborative Camouflaged Object Detection: A Large-Scale Dataset and Benchmark.

In this article, we provide a comprehensive study of a new task called collaborative camouflaged object detection (CoCOD), which aims to simultaneously detect camouflaged objects with the same properties from a group of relevant images. To this end, we meticulously construct the first large-scale dataset, termed CoCOD8K, which consists of 8528 high-quality and elaborately selected images with object mask annotations, covering five superclasses and 70 subclasses. The dataset spans a wide range of natural and artificial camouflage scenes with diverse object appearances and backgrounds, making it a very challenging dataset for CoCOD. Besides, we propose the first baseline model for CoCOD, named bilateral-branch network (BBNet), which explores and aggregates co-camouflaged cues within a single image and between images within a group, respectively, for accurate camouflaged object detection (COD) in given images. This is implemented by an interimage collaborative feature exploration (CFE) module, an intraimage object feature search (OFS) module, and a local-global refinement (LGR) module. We benchmark 18 state-of-the-art (SOTA) models, including 12 COD algorithms and six CoSOD algorithms, on the proposed CoCOD8K dataset under five widely used evaluation metrics. Extensive experiments demonstrate the effectiveness of the proposed method and the significantly superior performance compared to other competitors. We hope that our proposed dataset and model will boost growth in the COD community. The dataset, model, and results will be available at: https://github.com/zc199823/BBNet-CoCOD.

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.

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.

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.

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.

Associations of the serum kynurenine pathway metabolites with P50 auditory gating in non-smoking patients with first-episode schizophrenia.

Objective: Our study aimed to investigate the associations between the serum level of kynurenine pathway (KP) metabolites and P50 auditory gating in non-smoking patients with first-episode schizophrenia (FES). Materials and methods: In this study, 82 non-smoking patients with FES and 73 healthy controls (HC). P50 auditory gating was measured using a fully functional digital 64-channel EEG system, and the components included S1 amplitude, S2 amplitude, gating ratio (S2/S1), and amplitude difference (S1-S2). Serum levels of kynurenine and kynurenine acid were assessed using a combination of liquid chromatography with tandem mass spectrometry. Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Results: The serum kynurenine (251.46 ± 65.93 ng/ml vs. 320.65 ± 65.89 ng/ml, t = -6.38, p < 0.001), and kynurenine acid levels (5.19 ± 2.22 ng/ml vs. 13.26 ± 4.23 ng/ml, t = -14.73, p < 0.001), S1 amplitude [2.88 (1.79, 3.78) µV vs. 3.08 (2.46, 4.56) µV, Z = -2.17, p = 0.030] and S1-S2 [1.60 (0.63, 2.49) µV vs. 1.92 (1.12, 2.93) µV, Z = -2.23, p = 0.026] in patients with FES were significantly lower than those in HC. The serum kynurenine and kynurenine acid levels were negatively associated with S1-S2 (r = -0.32, p = 0.004 and r = -0.42, p < 0.001; respectively) and positively correlated with S2/S1 ratio (r = 0.34, p = 0.002 and r = 0.35, p = 0.002; respectively) in patients. Conclusion: Our findings suggested that neuroactive metabolites of the KP might play an important role in sensory gating deficit in first episode patients with schizophrenia. Furthermore, metabolites of the KP may be a new target for the treatment of cognitive impairments in schizophrenia.