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.

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.

Transient upregulation of immune activity induced by adolescent social stress is involved in cognitive deficit in adult male mice and early intervention with minocycline.

Increasing evidence shows that the developmental perturbation of immune activity can lead to long-lasting neurodevelopmental and behavioral abnormalities. In our previous study, we found that deficiencies of microglia and TNFα in the medial prefrontal cortex (mPFC) were involved in the impairment of cognitive flexibility induced by adolescent social stress in adult mice. It remains unclear how and when immune changes occur following adolescent stress exposure and whether it is possible to prevent the delayed occurrence of cognitive impairment through early immune intervention. Firstly, the present study investigated the time courses of microglia and TNFα changes in the mPFC following adolescent social stress. The results showed that compared to the controls, stress-exposed animals showed parallel variations in the protein expression of ionized calcium-binding adaptor molecule 1 (Iba1), a biomarker specific to microglia, and TNFα in the mPFC, with a transient increase during stress exposure, then a gradual decrease after the end of stress, leading to a significantly decreased level in adulthood. We further investigated the preventive effect of chronic treatment with the immune inhibitor minocycline during stress exposure on the cognitive and molecular alterations induced by adolescent social stress. The results showed that minocycline prevented the delayed cognitive deficit and the decreased immune changes in the mPFC of previously stressed adult mice. These results suggest that the transient upregulation of microglia and TNFα in the mPFC induced by adolescent social stress may participate in the development of cognitive flexibility deficit and that immunomodulation may act as a potential target for the early prevention of cognitive deficits in psychiatric disorders.

Deficiencies of microglia and TNFα in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence.

The crucial roles played by microglia and their release of cytokines in the regulation of brain maturation are increasingly being recognized. Adolescence is a unique period characterized by continued brain maturation, especially in the area of the prefrontal cortex. Our previous studies showed that adolescent social stress induced impairment in extradimensional set-shifting (EDS), a core component of cognitive flexibility mediated by the medial prefrontal cortex (mPFC) in adult mice. The present study further determined the role of microglia and the inflammatory cytokine tumor necrosis factor alpha (TNFα) in cognitive dysfunction. Accompanied by a deficit in EDS in adulthood, previously stressed mice showed significant reductions in the expression of the microglial molecular biomarker Iba1, cell numbers, and the levels of TNFα mRNA and protein in the mPFC. Pharmacological inhibition of TNFα signaling by direct injection of a neutralizer into the mPFC also specifically impaired EDS performance. Moreover, the cognitive and immune alterations in previously stressed adult mice were ameliorated by both acute LPS and chronic antidepressant treatment. Together, our data suggest that microglia and TNFα play important roles in cognitive flexibility and can provide attractive therapeutic targets for the treatment of cognitive deficits in psychiatric disorders.

Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference.

Abnormal BDNF signaling contributes to the structural and behavioral plasticity induced by drugs of abuse. However, the mechanisms regulating expression of Bdnf in drug addiction remain elusive. In the present study, using the conditioned place preference (CPP) model, we showed that expression of Bdnf IV is upregulated in the nucleus accumbens (NAc) of conditioned animals while Bdnf I is upregulated in cocaine-treated mice irrespective of conditioning. The methylation level of a putative c-MYB binding site in the promoter region of Bdnf IV was significantly decreased in the NAc under cocaine CPP conditioning but remained unchanged without conditioning, concurrently with increased binding of c-MYB to this site. Exon IV promoter/luciferase reporter assays revealed that transactivation of Bdnf by c-MYB was blocked by methylation of this c-MYB binding site. Administration of methionine, a precursor of SAM, inhibited cocaine CPP, reversed demethylation of c-MYB binding site and induction of Bdnf IV expression by cocaine CPP. Our results imply that Bdnf IV demethylation at c-MYB binding site is involved in cocaine-triggered seeking behavior, whereas Bdnf I responds to the immediate pharmacological effects of cocaine.

Identification of a novel missense (C7W) mutation of SOD1 in a large familial amyotrophic lateral sclerosis pedigree.

Mutations of Cu-Zn superoxide dismutase (SOD1) have rarely been identified in Chinese patients with amyotrophic lateral sclerosis (ALS). We recently initiated a program to screen mutations of SOD1, TARDBP, and C9orf72 genes, the most commonly mutated genes in ALS patients in Western countries, in Chinese ALS patients. In this study, we report a novel missense SOD1 mutation with a substitution of tryptophan for cysteine at the seventh amino acid (p.C7W, traditionally named p.C6W) based on HUGO Gene Nomenclature in a familial ALS pedigree. We also found that the activities of SOD1 were significantly decreased in the C7W patient and the carriers of the family, compared with the SOD1 activities of normal family members. Compared with reported C7G and C7S patients, analysis of phenotype revealed relatively mild disease phenotypes in C7W patients, which is correlated with less deteriorated alteration in protein structure. Like those of many other familial ALS families, variable clinical phenotypes in the C7W intrafamily suggest that potential genetic modifiers may contribute to this disease.