The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

Executive functions in non-suicidal self-injury comorbid first-episode and drug-naïve depression among adolescents.

Executive functions(EFs) may be associated with the emergence of non-suicidal self-injury(NSSI) due to their role as behavior controllers. EFs includes three core cognitive processes: inhibitory control, working memory, and cognitive flexibility(i.e. the ability to selectively alter cognitive strategies to generate appropriate behavior in the changing environment). This study aimed to systematically explore the three core EFs in depressed adolescents with NSSI. The data was obtained from the baseline data of the Chinese adolescent depression Cohort. The adolescents underwent cognitive assessments to yield domain-specific scores in EFs using the Digit Span Backward test(DSB), the Stroop Color-word interference test- color-word condition(Stroop-CW), and the Wisconsin Card Sorting tests(WCST). The significant differences in WCST scores were found between the NSSI group and the non-NSSI group. NSSI frequency was moderately positively correlated with total errors and negatively correlated with the number of categories completed. The number of categories completed in the "≥200″ NSSI frequency group was significantly lower than that in the "≤10″ NSSI group. The current findings suggested that depressed adolescents who had engaged in NSSI have poorer cognitive flexibility performance compared to adolescents without NSSI. As the frequency of NSSI increased, cognitive flexibility might become worse. These results provide evidence of a connection between executive dysfunctions and NSSI in depressed adolescents.

Differences in Non-suicidal Self-injury Behaviors between Unipolar Depression and Bipolar Depression in Adolescent Outpatients.

OBJECTIVE: Non-suicidal self-injury (NSSI) has a higher prevalence in adolescents with depressive disorders than in community adolescents. This study examined the differences in NSSI behaviors between adolescents with unipolar depression (UD) and those with bipolar depression (BD). METHODS: Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China. The methods, frequency, and function of NSSI were assessed by Functional Assessment of Self-Mutilation. The Beck Suicide Ideation Scale was used to evaluate adolescents' suicidal ideation, and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms. RESULTS: The UD group had higher levels of depression (19.16 vs.17.37, F=15.23, P<0.001) and anxiety symptoms (17.73 vs.16.70, F=5.00, P=0.026) than the BD group. Adolescents with BD had a longer course of NSSI than those with UD (2.00 vs.1.00 year, Z=-3.39, P=0.001). There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups. Depression (r=0.408, P<0.01) and anxiety (r=0.391, P<0.01) were significantly and positively related to NSSI frequency. CONCLUSION: Adolescents with BD had a longer course of NSSI than those with UD. More importantly, NSSI frequency were positively and strongly correlated with depression and anxiety symptoms, indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents' NSSI behaviors.

Effect of HD-tDCS on white matter integrity and associated cognitive function in chronic schizophrenia: A double-blind, sham-controlled randomized trial.

Schizophrenia is a disabling major mental disorder, which includes critical deficits in cognitive function, for which no effective intervention currently exists. The aim of our double-blind, randomized, sham-controlled trial was to evaluate the effects of high-definition transcranial direct current stimulation (HD-tDCS) on the cognitive deficits in schizophrenia. This study sample consisted of 56 individuals with chronic schizophrenia, randomly allocated to either the active stimulation or sham group. The treatment consisted of ten consecutive days of HD-tDCS, 20 min/day, applied over the left dorsolateral prefrontal lobe. Changes in clinical outcomes, cognitive assessments, and diffusion tensor imaging were evaluated pre- to post-intervention. Matched-healthy controls (HCs) were included to identify white matter changes in patients with schizophrenia before treatment. Compared to HCs, schizophrenia was associated with reduced integrity of the white matter tracts of the corpus callosum and corona radiata. HD-tDCS enhanced integrity in the corpus callosum and anterior and superior corona radiata, which was associated with the change in cognitive performance. HD-tDCS offers a potential approach to improve cognition deficits in schizophrenia through a modulatory effect on white matter tracts. Given the lack of approved treatments for cognitive deficits, these findings are clinically relevant.

The Changes of Histone Methylation Induced by Adolescent Social Stress Regulate the Resting-State Activity in mPFC.

Early-life stress can lead to sustained alterations in regional resting-state brain functions, but the underlying molecular mechanism remains unclear. Stress can also induce sustained changes in epigenetic modifications across brain regions, which are not limited to a few genes; rather, they often tend to produce global levels of change. The functional implication of these changes also remains to be elucidated. We hypothesize that global epigenetic changes may partly modulate the resting-state functions of brain regions to influence behavior. To test this hypothesis, we used an adolescent social stress (ASS) model in mice and examined the relationship between epigenetic modifications and regional resting-state brain activity using resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that, compared to the control mice, the stressed mice showed increased anxiety and social avoidance behaviors and greater levels of dimethylation of histone H3 at lysine 9 (H3K9me2) in the medial prefrontal cortex (mPFC). In addition, the resting-state activity represented by the amplitude of low-frequency fluctuation (ALFF) was significantly lower in the mPFC of stressed mice. To verify the relationship of H3K9me2 and ALFF, the specific inhibition of H3Kme2 was performed by using the drug UNC0642, which reversed the anxiety behavior induced by ASS and significantly increase the ALFF value of mPFC in both normal and ASS animals. Our study is the first to report an association between histone modifications and rs-fMRI findings, providing a new perspective for understanding of the significance of regional brain epigenetic changes and a possible molecular explanation for rs-fMRI findings.

An App knock-in rat model for Alzheimer's disease exhibiting Aß and tau pathologies, neuronal death and cognitive impairments.

A major obstacle in Alzheimer's disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The App knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiar App mutations and humanized Aß sequence knocked into the rat App gene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of Aß plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. This App knock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics.

Association of altered cortical gyrification and psychopathological symptoms in patients with first-episode drug-naïve schizophrenia.

Altered brain gyrification in diverse cortical regions has been reported in patients with schizophrenia, which possibly reflects deviations in early neurodevelopment. The main purpose of this study was to examine the relationship between clinical symptoms and abnormal cortical gyrification in drug-naïve patients with schizophrenia in a Chinese Han population. We calculated the whole-brain cortical gyrification of 41 patients with first-episode drug-naïve schizophrenia and 30 age- and sex-matched healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychopathology of patients with schizophrenia. Our results showed that compared to healthy controls, patients had higher cortical gyrification in the left lateral occipital cortex, but lower cortical gyrification in the left transverse temporal cortex. Moreover, the cortical gyrification in the left entorhinal cortex and left fusiform were both positively correlated with the general psychopathology of PANSS. Our findings indicate that abnormal cortical gyrification has occurred in the early stage of schizophrenia, suggesting that abnormal cortical gyrification may play an important role in the pathogenesis and symptomatology of schizophrenia.

Association between empathy and clinical symptoms in chronic schizophrenia: A large sample study based on Chinese Han population.

BACKGROUND: In patients with schizophrenia, clinical symptoms and cognitive impairment are its core features, both of which have a significant impact on the prognosis and functional outcome. Empathy, as an important social cognition, has been found to be associated with the clinical symptoms in schizophrenia, but the conclusions on this issue are inconsistent. Therefore, this study will continue to explore it through a large sample of inpatients with chronic schizophrenia in the Chinese Han population. METHODS: We obtained the sociodemographic characteristics of 987 inpatients, measured their clinical symptoms using the Positive and Negative Syndrome Scale (PANSS), and assessed their self-reported empathy using the Interpersonal Reactivity Index (IRI). The factor score for negative symptoms (FSNS) of PANSS was additionally calculated. RESULTS: Correlation and linear regression analysis showed that patients' PANSS scores were widely correlated with their IRI scores. In particular, the negative symptoms of patients were significantly correlated to IRI total score (r = -0.131, p < .001) and subscales such as Perspective Taking (PT) (r = -0.233, p < .001). FSNS had close relationships with empathy as well. There are also many significant associations between other dimensions, such as general psychopathology and Perspective Taking (PT) or Fantasy (FS) (all p < .05). CONCLUSIONS: Our results indicated that clinical symptoms, especially negative symptoms, were closely related to their current empathy in patients with schizophrenia, suggesting that the severity of clinical symptoms may be a powerful factor in predicting social cognition such as empathy of schizophrenia.

Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.

Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.

Association of negative symptoms with cognitive impairment in Chinese Han patients with chronic schizophrenia.

OBJECTIVE: Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. METHODS: We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. CONCLUSIONS: Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia.KEYPOINTSThis study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain.Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose.There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia.The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.

Suicide attempts in Chinese Han patients with schizophrenia: cognitive, demographic, and clinical variables

Objective: The purpose of this study was to investigate the lifetime suicide attempt rate, clinical characteristics and cognitive function of Chinese patients with chronic schizophrenia who had attempted suicide. Methods: We collected data from 908 schizophrenia inpatients about suicide attempts through interviews with the patients and their families, as well as through medical records. All patients were assessed with the Positive and Negative Syndrome Scale, the Rating Scale for Extrapyramidal Side Effects, the Abnormal Involuntary Movement Scale, and the Repeated Battery for the Assessment of Neuropsychological Status. Results: Of this sample, 97 (10.68%) had attempted suicide. Patients who had attempted suicide were younger, had longer illness duration, and more severe general psychopathology and depressive symptoms than those who had not. Logistic regression analysis confirmed that suicide attempts were correlated with age, smoking, and depression. No cognitive performance differences were observed between patients who had and had not attempted suicide. Conclusions: In China, patients with chronic schizophrenia may have a higher prevalence of lifetime suicide attempts than the general population. Some demographic and clinical variables were related to suicide attempts in patients with chronic schizophrenia.

P50 inhibition defects with psychopathology and cognitive impairment in patients with first-episode drug naïve schizophrenia.

BACKGROUND: Many studies have announced that P50 inhibition defects represent sensory gating deficits in schizophrenia, but studies seldom have searched the correlation between P50 inhibition defects and the psychopathology or cognitive impairment of patients with first-episode, drug naïve (FEDN) of schizophrenia. In this study, we investigated the auditory sensory gating deficits in a large number of Han patients with FEDN schizophrenia and their correlation with clinical symptoms and cognitive impairment. METHODS: A total of 130 patients with FEDN schizophrenia and 189 healthy controls were recruited in this study. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to score the psychopathology of the patients, and P50 inhibition was recorded using the 64-channel electroencephalography (EEG) system. RESULTS: Patients exhibited significantly longer S1 and S2 latency, lower S1 and S2 amplitudes and lower P50 difference than healthy controls (all p < 0.05). Significant correlations existed between S1 latency and PANSS negative symptoms or cognitive factor, P50 ratio and general psychopathology, P50 ratio and PANSS total score, P50 difference and general psychopathology, and P50 difference and PANSS total score (all p < 0.05). Multiple regression analysis revealed that S1 latency, sex, age, and education were contributors to negative symptom score (all p < 0.05). S1 latency, S2 latency, sex, age, and smoking status were contributors to cognitive factor (all p < 0.05). CONCLUSIONS: Our results show that patients with FEDN schizophrenia have P50 inhibition defects, which may be related to their psychopathological symptoms and cognitive impairment.

BDNF affects the mediating effect of negative symptoms on the relationship between age of onset and cognition in patients with chronic schizophrenia.

The age of onset of schizophrenia is related to variability in cognitive function and clinical characters, and negative symptoms and cognitive function share similar features that could be closely connected. Alterations in brain-derived neurotrophic factor (BDNF) expression and the Val66Met (rs6562) polymorphism are involved in the pathogenesis of the disease, but few studies have explored its influence on the associations of age of onset, cognitive function and clinical symptoms in schizophrenia. The clinical symptoms of a total of 573 patients with chronic schizophrenia were assessed by using the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The serum BDNF level and Val66Met polymorphism were measured after the assessment. Our results showed the following: (1) patients with an earlier age of onset exhibited more negative symptoms and cognitive deficits, as well as lower levels of serum BDNF; (2) negative symptoms and cognitive function showed negative and positive correlations with age of onset, respectively, and worse cognitive function was associated with a high level of negative symptoms and a low level of serum BDNF; and (3) the moderated mediation analyses indicated that negative symptoms partially mediated the relationship between age of onset and cognitive deficits, which was moderated by serum BDNF. The mediating effect of negative symptoms exhibited a Met allele dose-dependent tendency. These results indicate that age of onset, cognitive function, and clinical symptoms of schizophrenia exhibit different relationships under different serum BDNF levels and BDNF Val66met polymorphisms.

Prevalence of obesity and clinical and metabolic correlates in first-episode schizophrenia relative to healthy controls.

OBJECTIVE: People with schizophrenia exhibit a high obesity rate. However, little is known about the prevalence of obesity and its relationship with clinical symptoms and metabolic indicators in first-episode drug-naïve (FEDN) schizophrenia. METHODS: Demographic and lipid parameters were gathered from 297 FEDN schizophrenia and 325 healthy controls. The patients' symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: The obesity rate of FEDN patients was 10.77%, similar to that of controls (10.5%). The prevalence of overweight plus obesity of patients was 44.8%, significantly higher than that of controls (36.6%). Compared with non-obese patients, obese patients had higher levels of cholesterol (4.81 ± 0.93 vs 4.22 ± 1.00 mmol/L), triglyceride (0.27 ± 0.21 vs 0.14 ± 0.24 mg/dL), low-density lipoprotein (0.48 ± 0.12 vs 0.40 ± 0.12 mg/dL), greater ratio of triglyceride/high-density lipoprotein (2.01 ± 1.23 vs 1.44 ± 1.26), and higher PANSS positive symptom subscale score (29.81 ± 6.29 vs 27.05 ± 6.15), general psychopathology subscale score (70.75 ± 11.74 vs 66.87 ± 11.37), and total score (149.81 ± 21.08 vs 140.64 ± 21.58), but lower high-density lipoprotein level (1.09 ± 0.21 vs 1.27 ± 0.34 mg/dL) (all p < 0.05). Correlation analysis revealed that body mass index (BMI) was positively correlated with triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride/high-density lipoprotein ratio, PANSS positive symptoms, general psychopathology, and total scores (all p < 0.05, r = 0.124 ~ 0.335). Multiple regression analysis confirmed that PANSS positive symptoms, total score, and cholesterol level were significantly associated with BMI (all p < 0.05, ß: 0.126-0.162). CONCLUSION: There was no significant difference in the prevalence of obesity between FEDN patients and the control group. Moreover, BMI was positively associated with positive symptom severity in FEDN patients.

mPFC GABAergic transmission mediated the role of BDNF signaling in cognitive impairment but not anxiety induced by adolescent social stress.

Depression with comorbid anxiety or cognitive symptoms can vary in terms of symptoms, pathophysiology and antidepressant efficacy, but the underlying neurobiological mechanisms remain to be elucidated. Previous studies from our group and others have shown that as a classic animal model of depression, adolescent social stress (ASS) could stably induce a variety of emotional and cognitive alterations in adult animals, and accompanied by transcriptional decrease in brain-derived neurotrophic factor (BDNF) total and promoter IV levels in the medial prefrontal cortex (mPFC). The present study further identified the GABAergic synaptic and molecular changes downstream of BDNF signaling impairment in the mPFC and roles in various behavioral phenotypes induced by ASS. We found that ASS induced a set of emotional and cognitive symptoms, including decreased social interest, impaired cognitive function, and increased anxiety-like behavior, as well as decreased GABAergic transmission in the mPFC. The specific deletion of BDNF promoter IV directly caused impairments in social interest, cognitive function, and inhibition of GABAergic transmission, but no changes in anxiety-like behavior. Acute microinjections of tropomyosin-related kinase B (TrkB) agonists into the mPFC and chronic antidepressant treatment ameliorated the changes in social behavior and cognition, as well as the reduction in GABAergic synaptic transmission in the mPFC, but not anxiety in previously stressed adult mice. These results suggest that the downstream GABAergic transmission of BDNF signaling in the mPFC involved in depression with comorbid cognitive dysfunction induced by ASS and can be used as a therapeutic target for the treatment of cognitive dysfunction in depression. This article is part of the special issue on Stress, Addiction and Plasticity.

The interactive effect of genetic polymorphisms of IL-10 and COMT on cognitive function in schizophrenia.

Dopaminergic and inflammatory systems have been proven to play an important role in the cognitive deficits of schizophrenia. Although increasing evidence indicates two systems have strong interaction, the relevant research on this interaction is still limited. Catechol-o-methyltransferase (COMT) and Interleukin-10 (IL-10) play critical functions in dopaminergic and inflammatory systems respectively, and their genetic polymorphisms are both associated with cognitive function. However, the interactive effect of their genetic polymorphisms has not been investigated. In this study, COMT Val158Met (rs4680) and IL-10 -592A/C (rs1800872) polymorphisms were measured in patients with chronic schizophrenia (n = 244) and healthy controls (n = 396), and their cognitive functions were assessed using the "Repeatable Battery for the Assessment of Neuropsychological Status" (RBANS). We found that IL-10 alone had no effect on cognitive function, while COMT affected language ability and interacted with the schizophrenia (case vs control) or sex in multiple RBANS indexes. Additionally, we found there was a significant interactive effect between IL-10 and COMT polymorphisms on multiple cognitive indexes of RBANS. In detail, the analysis showed that the IL-10 polymorphism had opposite effects on cognitive function in different COMT genotype carriers; meanwhile, the polymorphism of COMT only had a significant effect on cognitive function in IL-10 C carriers. And this interaction was more significant in schizophrenia than in controls. Our study discovered for the first time, there is an interactive effect between IL-10 and COMT genetic polymorphisms on cognitive function, which is valuable for further investigations and drug administrations associated with both systems.

The Role of Microglial CX3CR1 in Schizophrenia-Related Behaviors Induced by Social Isolation.

According to the microglial hypothesis of schizophrenia, the hyperactivation of microglia and the release of proinflammatory cytokines lead to neuronal loss, which is highly related to the onset of schizophrenia. Recent studies have demonstrated that fractalkine (CX3CL1) and its receptor CX3CR1 modulate the function of microglia. Thus, the present study aimed to determine whether microglial CX3CR1 plays a role in schizophrenia-related behaviors. A classical animal model of schizophrenia, social isolation (from postnatal days 21-56), was used to induce schizophrenia-related behaviors in C57BL/6J and CX3CR1-/- mice, and the expression of the microglial CX3CR1 protein was examined in several brain areas of the C57BL/6J mice by Western blot analysis. The results revealed that social isolation caused deficits in the prepulse inhibition (PPI) in the C57BL/6J mice but not in the CX3CR1-/- mice and increased locomotor activity in both the C57BL/6J mice and the CX3CR1-/- mice. Moreover, the CX3CR1 protein level was increased in the medial prefrontal cortex, nucleus accumbens, and hippocampus of the isolated C57BL/6J mice. These findings suggested that the function of microglia regulated by CX3CR1 might participate in schizophrenia-related behaviors.

Association of cigarette smoking with cognitive impairment in male patients with chronic schizophrenia.

BACKGROUND: Previous studies have shown that patients with schizophrenia have higher smoking rates and worse cognitive function than healthy controls. However, there is no consistent conclusion about the relationship between smoking and cognitive impairment. OBJECTIVES: The main purpose of this study was to explore the effects of smoking on cognitive function by using MATRICS Cognitive Consensus Battery (MCCB) in Chinese male patients with schizophrenia. METHODS: There were 164 patients with chronic schizophrenia and 82 healthy controls. All subjects were interviewed about smoking status. The cognitive function was assessed by MCCB and Stroop tests. The Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Compared with healthy controls, patients had lower MCCB scores in all of its domain scores (all p < 0.05). In the patients, the scores of spatial span test (42.3 ± 11.6), digital sequence test (42.9 ± 10.6), and Hopkins Verbal Learning Test (42.2 ± 10.1) were lower in smokers than those in nonsmokers (all p < 0.05, effect size: 0.28-0.45). Logistic regression analysis showed that the smoking status of the patients was correlated with digital sequence score (p < 0.05, OR = 1.072, 95%CI: 1.013-1.134). Multivariate regression analysis showed that the spatial span total score (ß = - 0.26, t = - 2.74, p < 0.001) was associated with the duration of smoking in patients with schizophrenia. CONCLUSIONS: Our findings show that smoking patients with chronic schizophrenia exhibit more severe cognitive impairment than nonsmoking patients, especially in working memory and executive function.

Suicide attempts in Chinese Han patients with schizophrenia: cognitive, demographic, and clinical variables.

OBJECTIVE: The purpose of this study was to investigate the lifetime suicide attempt rate, clinical characteristics and cognitive function of Chinese patients with chronic schizophrenia who had attempted suicide. METHODS: We collected data from 908 schizophrenia inpatients about suicide attempts through interviews with the patients and their families, as well as through medical records. All patients were assessed with the Positive and Negative Syndrome Scale, the Rating Scale for Extrapyramidal Side Effects, the Abnormal Involuntary Movement Scale, and the Repeated Battery for the Assessment of Neuropsychological Status. RESULTS: Of this sample, 97 (10.68%) had attempted suicide. Patients who had attempted suicide were younger, had longer illness duration, and more severe general psychopathology and depressive symptoms than those who had not. Logistic regression analysis confirmed that suicide attempts were correlated with age, smoking, and depression. No cognitive performance differences were observed between patients who had and had not attempted suicide. CONCLUSIONS: In China, patients with chronic schizophrenia may have a higher prevalence of lifetime suicide attempts than the general population. Some demographic and clinical variables were related to suicide attempts in patients with chronic schizophrenia.

The clock-controlled chemokine contributes to neuroinflammation-induced depression.

The circadian rhythm plays a central role in immune function, and its disruption has been closely linked to the etiology of depression. However, the mechanisms underlying the association between depression and circadian rhythm remain unclear. We found that mice deficient of Per2, a central clock component of circadian output, were resilient to neuroinflammation-induced depressive behavior. After repeated central lipopolysaccharide (LPS) injections, MCP-1, MIP-1ß, and RANTES increased in wild type (WT) but not in Per2-deficient mice. In addition, intracerebroventricular injection of RANTES resulted in depression-like behavior, and Met-RANTES, a CCR5 antagonist, could reverse depression-like behavior induced by LPS treatments. These results indicated that the Per2 gene contributes to depression via chemokines, especially RANTES. Furthermore, BMAL1 expression decreased in LPS-treated Per2-deficient mice and BMAL1 could bind to the promoter of Rantes, indicating clock gene can act as a regulator for neuroinflammation. In conclusion, Rantes, a clock-controlled gene (CCG), is involved in clock-immunological mechanisms underlying the effects of Per2 on neuroinflammation-induced depression-like behavior.