Association between suicidal behavior and impaired glucose metabolism in first-episode drug-naïve patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) patients have been reported to have comorbid suicidal behavior (SB) and impaired glucose metabolism in early psychosis, but it is unclear whether impaired glucose metabolism plays a role in the occurrence of SB in patients with first-episode drug-naïve (FEDN) SZ. Therefore, our main aim was to examine the relationship between SB and glucose metabolism in FEDN SZ patients. METHODS: We recruited 319 FEDN SZ patients and collected information on their sociodemographic characteristics, clinical data, and glucose metabolism parameters. Participants' psychotic and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAMD), respectively. Fasting plasma glucose and insulin levels were also measured. RESULTS: The percentage of FEDN SZ patients with SB was 45.5% (145/319). Compared to SZ patients without SB, SZ patients with SB exhibited higher scores on HAMD, PANSS positive subscale, as well as higher levels of fasting plasma glucose, fasting plasma insulin, and homeostasis model assessment of insulin resistance index (all p<0.05). Logistic regression analysis indicated that increased levels of insulin resistance (adjusted OR = 1.920), body mass index (adjusted OR = 0.931), and PANSS general psychopathology (adjusted OR = 1.041) were independently associated with SB. The Receiver Operating Characteristic Curve showed an Area Under Curve value of 0.732 for the combination of three factors in regression model to distinguish between SB and non-SB. CONCLUSIONS: Our results indicate that fasting glucose, fasting insulin, and insulin resistance are strongly associated with SB in FEDN SZ patients, suggesting that glucose metabolism abnormalities may be potential biomarkers of SB in SZ patients. Regular monitoring of glucose metabolism variables is essential for suicide prevention.

Association of P50 with social function, but not with cognition in patients with first-episode schizophrenia.

Functional deficits including cognitive impairment and social dysfunction are the core symptoms of schizophrenia (SCZ), and sensory gating (SG) deficits may be involved in the pathological mechanism of functional deficits in SCZ. This study was to investigate the relationship between defective P50 inhibition and functional deficits in first-episode drug naïve (FEDN) SCZ patients. A total of 95 FEDN SCZ patients and 53 healthy controls (HC) were recruited. The Chinese version of UCSD Performance-Based Skills (UPSA), MATRICS Consensus Cognitive Battery (MCCB), and EEG system were used to assess the social function, cognitive performance, and P50 inhibition, respectively. The MCCB total score and eight domain scores were significantly lower in patients with FEDN SCZ than those in HC (all p < 0.05). The UPSA total score and financial skills scores were also significantly lower in SCZ patients than that in the HC (all p < 0.05). Compared with HC, patients with FEDF SCZ had a higher P50 ratio (all p < 0.05). There was no correlation between P50 components and MCCB scores in patients with FEDF SCZ. However, there was only a correlation between the P50 ratio and UPSA financial skills, communication skills, or total score in patients (all p < 0.05). Defective P50 inhibition in FEDN SCZ patients may be associated with social dysfunction but not cognitive impairment, suggesting that the social dysfunction and cognitive impairment of patients with FEDN SCZ may have different pathogenic mechanisms.

Diabetes mellitus in patients with chronic bipolar disorder: prevalence, clinical correlates and relationship with homocysteine.

Comorbid diabetes mellitus in patients with bipolar disorder may contribute to increased morbidity and mortality. To determine the prevalence of diabetes mellitus in bipolar disorder patients and its clinico-demographic and homocysteine correlates, we conducted a cross-sectional survey of 195 bipolar disorder inpatients. They received questionnaires, clinical measurements and laboratory tests to assess demographic characteristics, anthropometric variables, clinical variables and plasma homocysteine levels. The prevalence of diabetes mellitus (including type 1, type 2 and special types) in Chinese bipolar disorder patients was 14.9%. Analysis of variance or chi-square test showed that compared with non-diabetic bipolar disorder patients, diabetic bipolar disorder patients were older, more often married, had a longer duration of disease, took less olanzapine and had a higher frequency of hypertension. However, there were no significant differences in body mass index (BMI) and homocysteine levels between diabetic and non-diabetic bipolar disorder patients. Logistic regression analysis showed that marital status and duration of disease were independently associated with diabetes mellitus in patients with bipolar disorder after controlling for age, use of olanzapine, presence of hypertension, BMI and homocysteine levels. These findings shed light on the clinico-demographic correlates of the increased prevalence of diabetes mellitus in bipolar disorder patients, rather than the correlation with some metabolic risk factors.

A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms.

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. We used the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess clinical symptoms and cognition. Our results show that the COX2 rs5275 polymorphism was significantly correlated with SCZ and positive symptoms. After 12-week treatment, celecoxib significantly improved the PANSS total and three subscale scores of SCZ patients. Furthermore, patients with the rs5275 TT genotype had greater improvement in PANSS total score than patients carrying the C allele. However, no significant difference in RBANS total and subscale scores existed between the celecoxib and placebo groups at week 12. Our findings suggest that COX2 inhibitors may be promising therapeutics for clinical symptoms rather than cognitive impairment in first episode SCZ patients. COX2 rs5275 gene polymorphism may be implicated in the development and the efficacy of treating clinical symptoms in SCZ.Trial Registration Number: The trial was registered with www.clinicaltrials.gov (NCT00686140).

Sex difference in association between cognitive and P50 deficits in patients with chronic schizophrenia.

A large number of studies have reported that sensory gating disorders represented by P50 inhibition may be involved in the pathophysiological process of schizophrenia. However, few studies have explored the relationship between sensory gating disorders and cognitive dysfunction in patients with schizophrenia. This study aimed to explore sex differences in the relationship between cognitive and P50 deficits in patients with chronic schizophrenia, which has not been reported. A total of 183 chronic schizophrenia patients (128 males and 55 females) and 166 healthy controls (76 males and 90 females) participated in this study. The MATRICS Consensus Cognitive Battery (MCCB) was measured for cognitive function and P50 components for the sensory gating in all participants. The Positive and Negative Syndrome Scales (PANSS) was used to assess the psychopathological symptoms in patients. Female patients performed significantly better than male patients in several cognitive domains of MCCB (all p < 0.01). There were no significant differences in P50 components between male and female patients (all p > 0.05). Further analysis showed that in female patients, latency of S2 was negatively correlated with reasoning and problem-solving domain of MCCB (p < 0.05), and P50 ratio was negatively correlated with social cognition domain of MCCB (p < 0.05). In male patients, there was no any correlation between P50 and cognitive domains of MCCB. Our results suggest that there is a sex difference in the association between P50 deficiency and cognitive impairment in Chinese Han patients with schizophrenia.

Sex difference in association between tardive dyskinesia and cognitive deficits in patients with chronic schizophrenia.

BACKGROUND: Tardive dyskinesia (TD), a side effect due to long-term use of antipsychotic medication, is associated with cognitive impairment. Several studies have found sex differences in cognitive impairment in schizophrenia patients, while whether there are sex differences in cognitive performance in schizophrenia patients with TD has not been reported. METHODS: A total of 496 schizophrenia inpatients and 362 healthy controls were recruited for this study. We used the Positive and Negative Syndrome Scale (PANSS) to assess patients' psychopathological symptoms and the Abnormal Involuntary Movement Scale (AIMS) to assess the severity of TD. Cognitive function was measured in 313 of these inpatients and 310 of healthy controls using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS: Patients with schizophrenia performed worse in all cognitive domains than healthy controls(all p < 0.001). Compared to patients without TD, patients with TD had higher PANSS total, PANSS negative symptom subscale and AIMS scores (all p < 0.001), while RBANS total, visuospatial/constructional and attention subscale scores were significantly lower (all p < 0.05). In addition, the visuospatial/constructional and attention indices remained significantly lower in male patients with TD than those without TD (both p < 0.05), but these results were not observed in female patients. Moreover, visuospatial/constructional and attention indices were negatively correlated with total AIMS scores only in male patients (both p < 0.05). CONCLUSION: Our results suggest that there may be sex differences in cognitive impairment in schizophrenia patients with comorbid TD, indicating that female gender may have a protective effect on cognitive impairment in schizophrenia patients caused by TD.

P50 sensory gating, cognitive deficits and depressive symptoms in first-episode antipsychotics-naïve schizophrenia.

OBJECTIVE: Sensory gating P50 (SG-P50) may be involved in the pathophysiological mechanisms of impaired cognition in schizophrenia (SCZ). Comorbid depressive symptoms are common in SCZ patients and are also found to be associated with their cognitive impairment. However, it is unclear whether SG-P50 is abnormal in first episode antipsychotics naïve (FEAN) SCZ patients with depressive symptoms. Our aimed to investigate the relationships between SG-P50, depressive symptoms and neurocognition in FEAN-SCZ patients. METHODS: We recruited 103 FEAN-SCZ patients (depression: n = 63; non-depression: n = 40) and 55 healthy controls. SG-P50 was measured using the standard auditory dual-click (S1&S2) paradigm. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale-17 (HDRS-17). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Compared with non-depressive patients, depressive patients had a significantly larger S2 amplitude (p = 0.005) and a higher S2/S1 ratio at trend level (p = 0.075) after corrected. There were significant differences in the scores of CPT-IP and Mazes (NAB) between depressive and non-depressive FEAN-SCZ patients (both p values < 0.05). For all patients, the SG-P50 S2/S1 ratio was significantly correlated with HDRS-17 score (r = 0.23, p = 0.020) and MCCB-Symbol coding (r = -0.16, p = 0.043). For depressive FEAN-SCZ patients, S2 amplitude was an independent predictor of the MCCB-Mazes (NAB) (ß = -0.31, t = -2.52, p = 0.015). CONCLUSIONS: SG-P50 deficit may be an informational biomarker for depressive symptoms and neurocognitive impairments in FEAN-SCZ patients.

Sex differences in prevalence and clinical correlates of insomnia in Chinese patients with chronic schizophrenia.

OBJECTIVE: It is generally recognized that there are sex differences in many aspects of schizophrenia. The main purpose of this study was to investigate the sex differences in the prevalence and clinical correlates of insomnia in patients with chronic schizophrenia. METHODS: A total of 957 patients who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study (male/female = 630/327). Demographic, clinical, and insomnia data were collected using self-reported questionnaires. Fasting blood samples were collected to evaluate the status of blood lipids. Psychopathological symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The prevalence rate of insomnia in female patients with schizophrenia was significantly higher than that in male patients (17.3% for males and 26.3% for females; χ2 = 10.74, p = 0.001). Regression analysis showed that in male patients, insomnia was independently associated with severe PANSS positive symptoms, severe PANSS depressive factor, and high levels of low-density lipoprotein levels, while in female patients, insomnia was associated with low education level, high PANSS depressive factor, and high levels of apolipoprotein B levels. CONCLUSION: This study illustrates that insomnia is more frequent in female than male schizophrenia patients, and that there are differences in the clinical correlates of insomnia by sex, suggesting that sex differences should be considered in prevention and treatment strategies for coexisting insomnia in schizophrenia patients.

Smoking affects the association between cognitive impairment and P50 inhibition defects in patients with chronic schizophrenia: A case-control study.

OBJECTIVE: Smoking affects sensory gating, as assessed by the event related potential P50, which is evoked by auditory stimuli and is considered to be involved in the pathophysiology of schizophrenia (SCZ). However, few studies have compared sensory gating and cognitive performance between smoking and non-smoking SCZ patients in the Chinese Han population. METHODS: We recruited two groups of Chinese subjects: 128 male chronic SCZ patients and 76 male healthy controls, measuring cognition with the MATRICS Consensus Cognitive Battery (MCCB) and sensory gating with the P50 EEG components. Based on their smoking status, they were further divided into 4 subgroups: smoking SCZ patients, non-smoking SCZ patients, smoking healthy controls, and non-smoking healthy controls. We assessed psychopathological symptoms of the patients using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, SCZ patients had lower MCCB total score and scores of all 10 tests (all p < 0.05), while SCZ patients had higher S2 amplitudes and P50 ratios (both p < 0.05). When comparing smoking versus non-smoking SCZ patients, non-smokers had significantly better spatial span (p < 0.05). Furthermore, the S1 amplitude was negatively correlated with the Brief Visuospatial Memory Test (BVMT-R) in smoking patients (p < 0.05), while the S1 latency was negatively correlated with spatial span in non-smoking patients (p < 0.01). CONCLUSIONS: Our finding shows a difference in the relationship between sensory gated P50 and cognition in smoking and non-smoking SCZ patients, suggesting that nicotine may improve cognitive and P50 deficits in SCZ patients.

Association of Transferrin Gene Polymorphism with Cognitive Deficits and Psychiatric Symptoms in Patients with Chronic Schizophrenia.

A large amount of recent literature has focused on impaired iron homeostasis in the pathophysiology of schizophrenia. Specifically, microarray analysis has illustrated associations between the transferrin locus and schizophrenia. To elaborate on the effects of transferrin on schizophrenia and its psychiatric phenotypes, our study aimed to investigate whether transferrin gene polymorphism was correlated with cognitive deficits and clinical symptoms in schizophrenia. We recruited 564 patients with chronic schizophrenia and 422 healthy controls (HCs) in a Han Chinese population, collected phenotypic data, and genotyped the rs3811655 polymorphism of the transferrin gene. Our results showed that the rs3811655 polymorphism was related to cognitive performance in both patients and HCs, as well as negative symptoms in patients (all p < 0.05), and patients carrying at least one G-allele showed worsened cognition/severe negative symptoms (all p < 0.05). Further analyses also found that the rs3811655 polymorphism in combination with cognition may exert small but significant contributions to the negative (ß = −0.10, t = −2.48, p < 0.05) or total psychiatric symptoms (ß = −0.08, t = −1.92, p < 0.05) in patients. Our findings indicated that the rs3811655 polymorphism may be implicated in the cognitive deficits of schizophrenia and HCs as well as psychiatric symptoms in patients, which suggested the possible iron regulatory mechanism in the pathology of schizophrenia.

The inconsistent mediating effect of catechol O methyl transferase Val158Met polymorphism on the sex difference of cognitive impairment in schizophrenia patients.

Objective: Schizophrenia is a multifaceted mental disorder characterized by heterogeneous positive/negative symptoms and cognitive deficits. Sex differences have been reported in various aspects of the disease. However, the underlying genetic reasons remain unelucidated. Recent studies show that the influence of COMT Val158Met (rs4680) variation is sexually dimorphic. Thus, this study aims to explore whether there is an effect of the interaction between COMT Val158Met (rs4680) polymorphism and sex on patients' clinical characteristics and cognitive function. Materials and methods: We recruited 367 in patients with chronic schizophrenia (246 males and 121 females) and 419 healthy controls (172 males and 247 females). The cognitive performance was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the COMT Val158Met (rs4680) polymorphism is genotyped. The psychopathological symptoms of the patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Results: We find that male patients had a significantly higher proportion of carrying the Val allele and Val/Val carriers exhibited more severe positive symptoms and cognitive impairment than Met carriers. COMT Val158Met (rs4680) polymorphism inconsistently mediated the relationship between sex and cognitive performance in schizophrenia patients. Conclusion: These findings suggest that COMT Val158Met (rs4680) polymorphism is associated with the risk and severity of schizophrenia in a sexually dimorphic way and contributes more to the clinical symptoms and cognitive impairment in male patients with schizophrenia.

Tardive dyskinesia in Chinese patients with schizophrenia: Prevalence, clinical correlates and relationship with cognitive impairment.

OBJECTIVE: Tardive dyskinesia (TD) has a high prevalence and is one of the distressing side effects of antipsychotic medications. Few studies have explored the relationship between TD, clinical correlates, and cognition. The aim of this study was to assess the prevalence, clinical correlates and cognitive impairment of co-occurring TD in Chinese patients with schizophrenia. METHODS: We recruited 655 patients with chronic schizophrenia who met the DSM-IV diagnostic criteria for schizophrenia and collected clinical and demographic data. All patients were assessed using the Abnormal Involuntary Movement Scale (AIMS) for the severity of TD, Positive and Negative Syndrome Scale (PANSS) for psychopathological symptoms, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognition. RESULTS: The overall TD prevalence was 41.1%, 42.9% (246/574) in men and 28.4% (23/81) in women (χ2 = 6.1 df = 1, p < 0.05). There were significant differences in age, sex, duration of illness, number of hospitalizations, drug type, smoking and PANSS negative symptom subscore between TD and non-TD groups (all p < 0.05). Moreover, patients with TD scored lower for immediate memory, attention, delayed memory, and RBANS total scores (all p < 0.05). Logistic regression showed a significant correlation between TD and age, sex, drug type and attention subscore. CONCLUSION: Our results suggest that multiple demographic and clinical variables may be associated with the development of TD. Moreover, TD patients may exhibit more cognitive impairment than non-TD patients.

Demographics, clinical characteristics and cognitive symptoms of heavy smokers and non-heavy smokers in Chinese male patients with chronic schizophrenia.

Many studies have shown a high smoking rate and cognitive impairment in patients with schizophrenia. The effects of smoking and nicotine intake on cognitive function in schizophrenia are still controversial. In this study, we divided patients into heavy smoking and non-heavy smoking groups and compared the clinical characteristics and cognitive symptoms between the two groups in Chinese male patients with schizophrenia. A total of 154 heavy smoking patients and 372 non-heavy smoking patients were recruited. They completed a detailed questionnaire including general and socio-demographic data. Positive and Negative Syndrome Scale (PANSS) was rated for psychopathology. The Fagerstrom Test for Nicotine Dependence (FTND) was used to assess the degree of nicotine dependence. Heavy smokers were younger, started smoking earlier and had a higher FTND total score than non-heavy smoking patients. Moreover, we found that heavy smokers had significantly lower negative symptom scores and cognitive factor scores than non-heavy smokers. Logistic regression analysis showed that cognitive factor score and age of initial smoking were significantly associated with heavy smoking. Linear regression analysis showed that cognitive factor score, age of initial smoking and dose of antipsychotics were significant predictors of the amount of smoking. Our findings suggest that there are significant differences in some demographic and clinical variables between heavy and non-heavy smokers in Chinese male patients with chronic schizophrenia. Moreover, heavy smokers have less cognitive symptoms, suggesting that heavy smoking may be beneficial for cognition of patients with schizophrenia.

Leptin Methylation and mRNA Expression Associated With Psychopathology in Schizophrenia Inpatients.

Leptin involved in the regulation of dopaminergic neurons of the central nervous system may confirm the hypothesis of neurodevelopment in schizophrenic patients. However, specific genetic mechanisms are undefined. Therefore, we aimed to explore the regulation of DNA methylation of leptin promoters and mRNA expression in patients with schizophrenia. A cross-sectional study enrolled 40 patients and 40 healthy controls from the Beijing Huilongguan Hospital in China. The leptin methylation levels and mRNA expression were examined by highly sensitive mass spectrometry based on the MassARRAY System and real-time quantitative polymerase chain reaction (qPCR). The Positive and Negative Symptoms Scale (PANSS) was applied to estimate the clinical symptoms of patients. The LEP-CpG7 and CpG15 methylation in patients were significantly higher than in healthy controls (P < 0.05). The LEP-CpG11, CpG33.34.35, CpG36 methylation, and mRNA expression decreased significantly in patients compared with healthy controls (P < 0.05). After controlling gender, age, BMI, dose of antipsychotic and duration of illness, LEP-CpG7 methylation was negatively associated with PANSS positive symptoms subscore (r = -0.485, P = 0.005). In addition, LEP-mRNA expression was negatively correlated with PANSS total score (r = -0.385, P = 0.03) and positive subscale (r = -0.392, P = 0.026). Nevertheless, only the LEP-CpG7 methylation level remained negatively correlated to the PANSS positive subscore following multiple stepwise regression (ß = -17.071, P = 0.037). These results suggest that leptin methylation and mRNA expression might contribute to the pathogenesis of schizophrenia. LEP-CpG7 methylation may be negatively associated with positive symptoms in patients with schizophrenia.

Sex difference in association between insomnia and cognitive impairment in patients with chronic schizophrenia.

OBJECTIVE: Sex differences in schizophrenia have been noted across domains such as sleep and cognitive function； however, how they interact remains unclear. This study aimed to explore sex differences in the relationship between insomnia and cognitive function in patients with chronic schizophrenia. METHODS: 718 schizophrenia patients (480 males and 238 females) and 397 healthy controls were recruited. Insomnia was collected by a questionnaire. Insomnia severity index (ISI) was used to evaluate the severity of insomnia. The clinical symptoms and cognition were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. RESULTS: Schizophrenia patients showed significantly lower scores compared to healthy controls on the RBANS total score and four indexes (all p < 0.05). Male patients had a lower rate of insomnia, higher scores on the RBANS visuospatial/constructional, language, and total score than female patients (all P < 0.05). Insomnia patients had lower RBANS immediate memory, language, and total scores than non-insomnia patients, and the results only appeared in female patients (all P < 0.05). In addition, there were significant negative correlations between ISI and RBANS language and delayed memory in male patients, while ISI was significantly negatively correlated with RBANS immediate memory in female patients (all P < 0.05). CONCLUSION: Our findings suggest that there are sex differences in insomnia, cognitive performance, and their association in patients with chronic schizophrenia. These sex differences may have important potential clinical significance for the identification, evaluation, and treatment of insomnia in patients with chronic schizophrenia.

Association Between Hippocampal Subfields and Clinical Symptoms of First-Episode and Drug Naive Schizophrenia Patients During 12 Weeks of Risperidone Treatment.

Small hippocampal size may be implicated in the pathogenesis and psychopathology of schizophrenia (SCZ). However, does the volume of hippocampal subfields in SCZ patients affect response to antipsychotic treatment? In this study, we used risperidone to treat first-episode drug naïve (FEDN) SCZ patients for 12 weeks, and then explored the relationship between baseline hippocampal subfield volumes, as well as any changes in these hippocampal subfield volumes during treatment, and improvement in their psychopathological symptoms. By adopting a state-of the-art automated algorithm, the hippocampal subfields were segmented in 43 FEDN SCZ inpatients at baseline and after 12 weeks of risperidone monotherapy, as well as in 30 matched healthy controls. We adopted the Positive and Negative Syndrome Scale (PANSS) to assess psychopathological symptoms in patients at baseline and at post-treatment. Before treatment, SCZ patients had no significant differences in total or subfield hippocampal volumes compared with healthy volunteers. However, we found a significant correlation between a smaller left CA1 at baseline and a lower PANSS total score and general psychopathology sub-score at post-treatment (both p < 0.05). Furthermore, the left CA1 at baseline was significantly smaller in responders, who had >50% improvement in PANSS total score, than in non-responders (p < 0.05). Our results suggest that smaller left CA1 volume may be a predicator for improvement in psychotic symptoms of FEDN SCZ patients.

Polymorphism of Transferrin Gene Impacts the Mediating Effects of Psychotic Symptoms on the Relationship between Oxidative Stress and Cognition in Patients with Chronic Schizophrenia.

A series of studies indicated that iron distribution that partly derives from transferrin-bound iron in the peripheral nervous system in the brain may act in processes such as myelination and brain development. However, the relationship between schizophrenia, its psychotic symptoms, and the transferrin (TF) gene has not been systematically explored. Our study aimed to investigate how a particular polymorphism of the transferrin gene, rs3811655, affects the superoxide dismutase (SOD), malondialdehyde (MDA), psychotic symptoms, cognition, or the mediation model between antioxidant enzymes and cognition via symptoms. A total of 564 patients with chronic schizophrenia and 468 healthy control subjects were recruited. The psychotic symptoms and cognition were assessed by the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Furthermore, the serum SOD, MDA activity, and transferrin gene polymorphism were measured in patients. Our results demonstrated that patients with the G allele possessed more severe negative symptoms, worse cognitive performance with respect to attention, and higher serum Mn-SOD activity. Additionally, the rs3811655 polymorphism may act as a moderator in the association between Cu/Zn-SOD activity and cognition, as well as psychotic symptoms in patients suffering from schizophrenia. According to this study, the single nucleotide polymorphism (SNP) rs3811655 polymorphism may fail to contribute to the susceptibility of schizophrenia in an individual but is involved in the iron-induced oxidative stress disturbance and cognitive impairment in schizophrenia. This deepens our understanding of the critical role of iron-induced oxidative stress that might underlie the pathophysiology of schizophrenia.

Serum BDNF levels, glycolipid metabolism in deficit schizophrenia: A case-control study.

BACKGROUND: Few studies have compared serum BDNF and glycolipid profiles in patients with deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). We aimed to compare BDNF and glycolipid profiles between DS and NDS patients and healthy controls, and to investigate the relationship between BDNF, glycolipid profiles in DS and NDS patients. METHODS: A total of 591 patients with chronic schizophrenia (SZ) and 238 healthy controls participated in this study. According to Proxy for the Deficit Syndrome Scale, SZ patients were divided into DS (n = 158) and NDS (n = 273) patients. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: BDNF levels were significantly lower in SZ patients than those in healthy controls (7.81 ± 2.98 ng/ml vs. 11.96 ± 2.29 ng/ml, P < 0.01). Furthermore, BDNF levels were lower in DS group than those in NDS group (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Lower triglyceride levels were also an independent predictor for DS patients (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Serum BDNF levels were negatively associated with the severity of deficit syndrome in SZ patients (ß = -1.151, t = -2.559, P = 0.011). In DS group, triglycerides were associated with PANSS negative subscore (ß = -0.262, t = -2.994, P = 0.003) and depressive factor subscore (ß = 0.282, t = 2.146, P = 0.035). CONCLUSION: Serum BDNF and triglycerides may be informative biomarkers of DS in SZ patients. The differences in glycolipid metabolism patterns between DS and NDS patients indicate that deficit syndrome is an independent endophenotype of SZ patients.

Prevalence and clinical correlates of impaired glucose tolerance in first-episode versus chronic patients with schizophrenia.

AIM: Studies using oral glucose tolerance tests (OGTT) have shown that impaired glucose metabolism presents in the early stages of schizophrenia (SCZ). However, there is a lack of studies on changes in glucose metabolism with the stage of the disease. We first explored the features of glucose metabolic pattern at different phases of male SCZ. METHODS: We recruited 83 male first episode drug-naïve patients with SCZ (FEDN-SCZ) and 64 male chronic patients with SCZ (CH-SCZ), as well as 14 male healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. OGTT, fasting plasma glucose and lipid profiles of all participants were examined. RESULTS: While the impaired glucose tolerance (IGT) rate of male SCZ patients was higher than that of HC (P < .05), there was no difference in IGT prevalence between FEDN-SCZ and CH-SCZ. In male FEDN-SCZ, LDL (OR = 2.64, 95% CI = 1.11-6.29, P = .028) and PANSS total score (OR = 1.03, 95% CI = 1.00-1.06, P = .046) were positively correlated with IGT; in male CH-SCZ, BMI (OR = 1.7, 95% CI = 1.08-2.67, P = .023), PANSS total score (OR = 0.82, 95% CI = 0.70-0.96, P = .015) and positive symptoms (OR = 0.45, 95% CI = 0.20-0.99, P = .046) were significantly correlated with IGT. CONCLUSIONS: Our findings reflect different glucose metabolism patterns in different stages of SCZ.

Macrophage migration inhibitory factor as a potential novel biomarker for cognitive function in patients with first-episode schizophrenia.

OBJECTIVE: Cognitive impairment is prevalent in schizophrenia. Macrophage migration inhibitory factor which is released into the circulation under stress or inflammation, is associated with cognition and also plays an important role in immunity. However, no study has investigated the relationship between macrophage migration inhibitory factor and cognitive function in first-episode schizophrenia patients at baseline or after treatment. This study investigated the pre- and post-risperidone treatment correlations between serum macrophage migration inhibitory factor levels and cognitive function in first-episode schizophrenia patients. METHODS: A total of 83 first-episode schizophrenia patients who received risperidone monotherapy and 57 healthy controls - matched for sex, age, smoking status, education (years), marital status and waist-to-hip ratio - were included. Macrophage migration inhibitory factor levels were measured before and 10 weeks after treatment in the patient group and at baseline in the controls. Pre- and post-treatment cognitive functions in patients were assessed using the MATRICS Consensus Cognitive Battery. RESULTS: At baseline, macrophage migration inhibitory factor levels were significantly higher in first-episode schizophrenia patients than those in healthy controls (p < 0.01) and decreased in patients after 10 weeks of risperidone treatment compared with baseline (p < 0.05). The MATRICS Consensus Cognitive Battery total score and the sub-scores for the Trail Making Test, Symbol Coding, Letter Number Sequence, Maze and Brief Visuospatial Memory Test-Revised improved significantly after risperidone treatment. After controlling for age, sex, education, waist-to-hip ratio and smoking status, partial correlation analysis showed a positive correlation between baseline macrophage migration inhibitory factor levels and patients' baseline MATRICS Consensus Cognitive Battery verbal memory scores (r = 0.29, p = 0.01). Macrophage migration inhibitory factor changes correlated negatively with verbal memory changes (r = -0.26, p = 0.04). Multiple linear regression analysis identified a definite correlation between the changes in word memory test score and macrophage migration inhibitory factor level (ß = -0.09, p = 0.04). CONCLUSION: Macrophage migration inhibitory factor may be involved in the process of cognitive impairment in first-episode schizophrenia and repair mechanisms following risperidone treatment.