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).

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.

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.

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.

The relationship between cognitive impairment and superoxide dismutase activity in untreated first-episode patients with schizophrenia.

Objectives: Cognitive decline is an essential characteristic of schizophrenia and may be due to the disturbance between reactive oxygen species generation and antioxidant capacity. The study aimed to explore the association between cognitive deficits and antioxidant defence parameters in untreated first-episode patients with schizophrenia.Methods: We determined important antioxidant enzymes, total superoxide dismutase (SOD) and manganese SOD (MnSOD), and their relationship with cognitive impairment in 168 untreated patients with first-episode schizophrenia and 168 age- and sex-matched healthy controls. The evaluation of psychopathological symptoms of all patients was based on the Positive and Negative Syndrome Scale (PANSS). We measured cognitive function by the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) and activities of total SOD and MnSOD in all participants.Results: The results showed that untreated patients with first-episode schizophrenia had deficient cognitive functioning in four RBANS indices and total scores, except for the visuospatial/constructional index, as well as higher plasma total SOD activity compared with the control subjects. In addition, significant negative correlations were identified between MnSOD activity and attention index or RBANS total score in patients.Conclusions: Our results suggest that oxidative stress may be partly responsible for cognitive dysfunction in the early course of schizophrenia.

Prevalence, clinical correlates and risk factors associated with Tardive Dyskinesia in Chinese patients with schizophrenia.

Tardive Dyskinesia (TD) is a serious, nonrhythmic and iatrogenic movement disorder, and is a common comorbidity in patients with schizophrenia (SZ). The main goal of this study was to investigate the prevalence, clinical correlates, and risk factors of TD in Chinese patients with chronic SZ, which has not been fully studied. This study adopted a cross-sectional design. A total of 901 Chinese inpatients with SZ were recruited between 2008 and 2011. We used the Abnormal Involuntary Movement Scale (AIMS) to measure the severity of TD, and the Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathological symptoms of SZ. Blood samples were also collected for routine blood tests, including the levels of triglyceride (TG), cholesterol (CHO), HDL-cholesterol (HDL-CHO), LDL-cholesterol (LDL-CHO), Apolipoprotein A1 (ApoA1), and Apolipoprotein B (ApoB). Overall, 36% of patients with SZ had TD. Compared with the non-TD patients, the TD patients were more likely to be men, had older age, lower education level, higher smoking rate, higher hospitalization frequency, and longer duration of illness (DOI). Further, compared with the non-TD patients, the TD patients had higher PANSS total, PANSS negative subscale, and cognitive subscale scores, but had lower depressive subscale scores and lower mean levels of metabolic biomarkers, including TG, CHO, HDL-CHO, LDL-CHO, ApoA1 and ApoB. Moreover, binary regression analysis showed that antipsychotic type, BMI, gender, age, HDL-CHO, and ApoB were associated with TD. Our findings indicate that TD is a common movement disorder in patients with chronic SZ, with certain demographic and clinical variables being risk factors for the development of TD.

Association of depressive symptoms with cognitive impairment in patients with never-treated first-episode schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study.

OBJECTIVE: Depressive symptoms and cognitive dysfunction are common in patients with schizophrenia and depressive disorder. This study aimed at exploring whether and how depressive symptoms were correlated with neuro-cognitive impairment in patients with never-treated first-episode (NTFE) schizophrenia. METHODS: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to 79 patients and 80 healthy controls to assess neuropsychological function. For all patients, the 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, and the Positive and Negative Syndrome Scale (PANSS) was utilized to assess psychopathological symptoms. RESULTS: Thirty-nine patients (49.37%) met the criteria for comorbid depressive symptoms. The RBANS total and the four index scores in the patients were significantly lower than those in the healthy controls. Further, compared with patients without depressive symptoms, patients with depressive symptoms scored lower in attention index, but higher in PANSS general psychopathology and total scores. The HAMD-17 total score was significantly correlated with attention, PANSS total, and PANSS general psychopathology scores. Moreover, multiple regression analysis identified education and HAMD-17 score as the contributors to attention. CONCLUSION: Our results suggest that the rate of depressive symptoms in NTFE schizophrenia is high, which is correlated with neuro-cognitive impairment, especially attention and psychopathology.

Cognitive Deficits and Clinical Symptoms with Hippocampal Subfields in First-Episode and Never-Treated Patients with Schizophrenia.

Memory dysfunction and associated hippocampal disturbances play crucial roles in cognitive impairment of schizophrenia. To examine the relationships between cognitive function and the hippocampal subfields (HSs) in first-episode never-treated (FENT) schizophrenia patients, the HSs were segmented in 39 FENT patients and 30 healthy controls using a state-of the-art automated algorithm. We found no significant differences in any HSs between the patients and controls. However, multivariate regression analysis showed that the left cornu ammonis 1 (CA1), left hippocampal tail, left presubiculum, and right molecular layer contributed 40% to the variance of the PANSS negative symptom score. After adjusting for sex, age, education, and intracranial volume, the partial correlation analysis showed that the volumes of left CA1, CA3, CA4, molecular layer, granule cell layer and both left and right subiculum were negatively correlated with the MATRICS consensus cognitive battery (MCCB) Hopkins Verbal Learning Test (HVLT). Multiple regression analysis showed that the left CA1 and CA3 hippocampal abnormalities contributed 66% to the variance of the HVLT. Our results suggest no detectable HS deficits were found in FENT schizophrenia patients. However, the HSs may be involved in the symptoms and cognitive deficits of schizophrenia patients in the early phase of their illness.

Sex differences in the association between symptoms and superoxide dismutase in patients with never-treated first-episode schizophrenia.

OBJECTIVES: Considering the sex differences and oxidative stress in the pathophysiological mechanism of schizophrenia (SCZ), we explored the sex differences in clinical characteristics and superoxide dismutase (SOD) activity as well as their relationship in never-treated first-episode (NTFE) patients with SCZ in the Han Chinese population, which has not been reported yet. METHODS: Total SOD and manganese SOD (MnSOD) activities were examined in 165 NTFE patients with SCZ (male/female = 98/67) and 133 healthy controls (male/female =70/63). Psychopathological symptoms were evaluated by a five-factor model of the Positive and Negative Syndrome Scale (PANSS). RESULTS: SCZ patients had higher plasma total SOD activity than healthy controls (p < .01). In healthy controls, the total SOD activity was significantly higher in males than that in females (p < .001), but not in patients group (p > .05). Further, Multiple regression analysis revealed that in male patients, the PANSS depressive factor was independently positively correlated with MnSOD or total SOD activity (both p < .01), while in female patients, the MnSOD activity was positively related to the PANSS positive symptom score (p < .05). CONCLUSIONS: Our findings indicate sex differences in the relationship between SOD activities and psychopathological symptoms in the early stage of SCZ.

BDNF serum levels and cognitive improvement in drug-naive first episode patients with schizophrenia: A prospective 12-week longitudinal study.

Abnormal brain-derived neurotrophic factor (BDNF) levels are involved in cognitive decline in patients with schizophrenia. The role of atypical antipsychotic risperidone in improving cognitive function remains unclear. The study aimed to investigate the effect of risperidone monotherapy on cognitive impairment in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were correlated to the improvement of cognition. 354 DNFE patients and 152 healthy controls were recruited, and we compared their serum BDNF levels and cognition shown on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). High and low BDNF subgroups were defined by median split. Then, 211 patients were treated with risperidone monotherapy for 12 weeks, and their serum BDNF levels and cognition were measured again after treatment. DNFE patients had poorer cognitive functions and lower BDNF levels compared to controls. Lower BDNF levels were correlated with delayed memory in DNFE patients with high baseline BDNF levels. After 12 weeks of treatment, risperidone significantly improved immediate memory, delayed memory and RBANS total scores and BDNF levels were slightly increased. In patients with low-BDNF, BDNF levels were significantly increased after risperidone treatment, while in patients with high-BDNF, BDNF levels were significantly decreased. In addition, baseline BDNF levels were associated with improvement of delayed memory and were a prognostic factor for the improvement of the delayed memory and RBANS total score in patients with high-BDNF. Our result suggests risperidone treatment can partially improve certain domains of the cognitive impairment and baseline BDNF levels are related to cognitive response to risperidone in DNFE patients with schizophrenia.

Sex-specific association between peripheral superoxide dismutase, BDNF and cognitive impairment in drug-naive first episode patients with schizophrenia.

Patients with schizophrenia (SCZ) have cognitive impairments across several domains. Cognition decline is related to the complex interrelationship between brain-derived neurotrophic factor (BDNF) and redox system imbalance. However, the effect of sex on cognitive impairment and biomarkers has not been fully studied in patients with drug-naïve first episode (DNFE) SCZ. 327 DNFE SCZ patients and 391 healthy controls were recruited, and the levels of BDNF and malondialdehyde (MDA) and the activities of total SOD, Mn-SOD, CuZn-SOD enzymes were measured. Cognitive function was measured by using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms by the Positive and Negative Syndrome Scale (PANSS). Patients performed worse on most cognitive tasks than controls, but there was no significant sex difference in cognitive function between patients and controls. Further analysis showed that a sex difference in MDA was found in controls rather than patients, indicating that MDA levels in men were higher than those in women in controls. Moreover, the Mn-SOD was significantly correlated with attention, language and RBANS total scores only in male patients. Multiple linear regression analysis showed that the interaction between BDNF and Mn-SOD or SOD was associated with RBANS language index score in male patients. Our results suggest that the interrelationship of BDNF with antioxidant mechanisms may contribute to the pathological mechanisms underlying cognitive deficits only in male DNFE patients with SCZ, but not in female patients.

Culture and differentiation of purified human adipose-derived stem cells by membrane filtration via nylon mesh filters.

Human adipose-derived stem cells (hASCs) cultured for 5 passages were filtered through nylon (NY) mesh filter membranes coated with and without extracellular matrix proteins to obtain the permeation solution. Subsequently, the culture media were filtered via the membranes to obtain the recovery solution. Then, the membranes were cultured in cell culture medium to obtain the migrated cells from the membranes. The hASCs in the permeation solution, through any type of NY mesh filter membrane having 11 and 20 µm pore sizes, had lower osteogenic differentiation ability than conventional hASCs cultured on tissue culture polystyrene (TCP) dishes for passage 5, whereas the hASCs purified by the membrane migration method through NY mesh filter membranes coated with recombinant vitronectin, which have 11 and 20 µm pore sizes, showed a higher proliferation speed as well as higher osteogenic differentiation potential than the conventional hASCs cultured on TCP dishes for passage 5. The membrane filtration and migration methods would be useful for cell sorting for specific cells, such as hASCs with high proliferation and high osteogenic differentiation ability, which do not need antibody binding or genetic modification of the cells for the specific isolation of the cells.

Elevated activity of plasma superoxide dismutase in never-treated first-episode schizophrenia patients: Associated with depressive symptoms.

Oxidative stress in excess may be engaged in the pathophysiological development of schizophrenia (SCZ). Previous research showed altered activity of superoxide dismutase (SOD) in patients suffering from SCZ, with inconsistent results. However, few studies have analyzed the relationship between SOD activity and psychopathological symptoms in never-treated first-episode (NTFE) patients with SCZ. The activities of manganese SOD (MnSOD) and total SOD were measured in a large sample of 166 NTFE patients with SCZ, and 133 healthy controls. The patients' symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), as well as the depressive and cognitive factors originated from the PANSS five-factor model. NTFE patients had significantly higher activities of MnSOD and total SOD than healthy controls (both p < 0.01). Correlation analysis displayed a notably positive correlation between both MnSOD or total SOD activities and the PANSS depressive factor, as well as between MnSOD activity and the PANSS general psychopathology subscale score (all p < 0.05). Stepwise multiple regression analysis revealed that both MnSOD and total SOD were independent factors affecting PANSS depressive factor and PANSS general psychopathology subscale score. Our findings suggest that increased SOD activity may be associated with comorbid depressive symptoms in NTFE patients with SCZ.

Interrelationships Between BDNF, Superoxide Dismutase, and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia.

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.

MTHFR Ala222Val polymorphism and clinical characteristics confer susceptibility to suicide attempt in chronic patients with schizophrenia.

Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism responsible for the high rate of suicidal behavior in SCZ remains poorly understood. MTHFR Ala222Val (C677T; rs 1801133) polymorphism has repeatedly demonstrated to play a pathological role in numerous mental disorders, but none of these studies focused on the susceptibility of suicidal behavior in SCZ. In the present cross-sectional study, we recruited 957 chronic inpatients with SCZ and 576 healthy controls to assess the psychopathological symptoms of SCZ and compare the frequency of the MTHFR Ala222Val genotype in both suicide attempters and non-attempters. Our results demonstrated no significant differences in MTHFR Ala222Val genotype and allele distributions between the SCZ patients and controls (p > 0.05), but showed a statistical significance in the distribution of Ala/Val genotype between suicide attempters and non-attempters (p < 0.05). Further logistic regression analysis showed that MTHFR Ala222Val genotype, psychopathological symptoms, number of cigarettes smoked per day and drinking status were related to suicide attempts in SCZ (p < 0.05). Our study demonstrated that MTHFR Ala222Val polymorphism and some clinical characteristics might confer susceptibility to suicide in patients with SCZ.

Sex Differences in the Prevalence and Clinical Features of Comorbid Depressive Symptoms in Never-Treated Chinese Patients With First-Episode Schizophrenia.

BACKGROUND: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²1 = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (ß = 0.75, t = 7.72, P < .001) and total score (ß = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (ß = 0.74, t = 8.45, P < .001), total score (ß = 0.47, t = 5.71, P < .001), and cognitive factor subscore (ß = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

Interleukin-3, symptoms and cognitive deficits in first-episode drug-naïve and chronic medicated schizophrenia.

Previous studies consistently showed that IL-3 signaling may be involved in the pathophysiology of schizophrenia. However, investigations of associations between IL-3 and the neurocognitive impairments are lacking, including the study of how this may vary with stage of illness. We recruited 45 first-episode drug-naïve (FE-Sz), 35 chronic medicated schizophrenia (Ch-Sz) and 40 healthy controls (HC) and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-3. Altered serum IL-3 levels were found in both patient groups compared with HC group (both p < 0.001). There were significantly lower neurocognitive scores on the RBANS and nearly all of its five subscales, except for Visuospatial/Constructional index in both FE-Sz and Ch-Sz patients vs healthy controls. Moreover, a significant reduction in Immediate memory index (p = 0.021) and a trend-level reduction in RBANS total score (p = 0.094) in Ch-Sz than FE-Sz patients. Interestingly, there was a significant negative correlation between IL-3 and the Immediate memory index only in Ch-Sz patients (p = 0.03). Our findings showed that neurocognitive impairments present in schizophrenia emerge during the first episode with further diminished functioning with disease progression, and IL-3 may be involved in the immediate memory deficits in the chronic phase of schizophrenia.

BDNF Polymorphisms Are Associated With Cognitive Performance in Schizophrenia Patients Versus Healthy Controls.

BACKGROUND: Accumulating evidence has shown that brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of schizophrenia. Moreover, BDNF genetic variants, especially the Val66Met polymorphism, may influence specific aspects of human cognition. This study aimed to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and cognitive impairments in patients with schizophrenia in a Han Chinese population. METHODS: Four polymorphisms (rs6265, rs12273539, rs10835210, and rs2030324) of the BDNF gene were analyzed in a case-control study of 1,887 Han Chinese individuals (844 patients meeting DSM-IV diagnosis of schizophrenia and 1,043 healthy controls). Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in 598 patients and 434 controls. The current study was conducted from 2008 to 2011. RESULTS: Significant differences in the genotype and allele frequencies between patients and controls were observed only for rs10835210 (both P < .05). Further, we found that the rs10835210 polymorphism had a significant effect on language performance only in schizophrenia (P < .05). However, BDNF rs12273539 played a stronger role in cognitive performance among both patients and healthy controls, especially on attention (P < .001) and the RBANS total score (P < .01). CONCLUSIONS: These findings suggest the role of these BDNF gene variants in susceptibility to schizophrenia and in some aspects of cognitive function.

Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia.

Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to chronic medicated patients with schizophrenia and examined the association of IL-3 with their psychopathological symptoms. Serum IL-3 levels were assessed in 55 FEDN patients, 52 chronic medicated patients and 43 healthy controls. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS). Serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). We found significantly lower IL-3 levels in FEDN patients than both chronic patients and healthy controls (both p<0.001), while IL-3 levels in chronic patients were markedly higher than in healthy controls. No significant association was observed between IL-3 and any clinical psychopathology in FEDN patients; however, we found a significant correlation between serum IL-3 levels and the PANSS general psychopathology subscore in chronic medicated patients (p<0.05). Decreased IL-3 levels in FEDN patients suggest that suppressed immune function may be associated with developing schizophrenia, but as the disease progresses IL-3 levels increase perhaps related to medication treatment or other factors that occur during chronic illness.

Cognitive impairments in first-episode drug-naive and chronic medicated schizophrenia: MATRICS consensus cognitive battery in a Chinese Han population.

Cognitive deficits are a core feature of schizophrenia and we examined the cognitive profile of first-episode and chronic schizophrenia in a Chinese Han population using the MATRICS Consensus Cognitive Battery (MCCB). We recruited 79 first-episode drug-naïve (FEDN) schizophrenia, 132 chronic medicated schizophrenia inpatients and 124 healthy controls. We assessed patient psychopathology using the Positive and Negative Syndrome Scale (PANSS). MCCB total score (p<0.01) and index scores of category fluency, trail making A, digital sequence, Hopkins Verbal Learning Test (HVLT), mazes, and Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were significantly higher in FEDN than in chronic patients (all p<0.05). FEDN exhibited relative weakness in continuous performance, whereas chronic patients exhibited relative weakness in mazes. Multiple regression analysis confirmed that in FEDN and chronic patients, total score and negative symptom of PANSS were independent contributors to MCCB total score, respectively. Our results not only demonstrate the applicability of the MCCB as a sensitive measure of cognitive impairment for schizophrenia patients in a Chinese Han population, but also suggest that the compromised cognition is present in the early stage of schizophrenia, some of which could be more severe in the chronic stage of illness.