Mei Hong Xiu

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9+/-2.0 ng/ml vs.11.9+/-2.3 ng/ml, p<0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3+/-2.3 ng/ml) compared to those with clozapine (10.2+/-2.0 ng/ml, p<0.001) and typical antipsychotics (10.0+/-2.1 ng/ml, p<0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta=-0.37, t=-3.15, p=0.001) and BDNF levels (beta=-0.26, t=-2.51, p=0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7+/-1.9 ng/ml for males vs.10.4+/-2.1 ng/ml for female, p<0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.

Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia

ObjectiveSeveral lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia.Materials and methodsWe recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale.ResultsBDNF levels were significantly lower in patients than controls (p < 0.001). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia.ConclusionOur findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory.

Gender differences in cognitive function of patients with chronic schizophrenia.

Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.

Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia

Oxidative stress may be involved in the pathophysiology of schizophrenia. No double-blind study has compared the effects of typical and atypical antipsychotics on both antioxidant enzyme activity and nitric oxide (NO) levels in schizophrenic patients. Seventy-eight inpatients with chronic schizophrenia were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Blood superoxide dismutase (SOD) and plasma NO levels were measured in patients and 30 normal controls. Our results showed that following a 2-week washout period, levels of SOD and NO were significantly increased in patients with schizophrenia compared to normal controls. Both risperidone and haloperidol equivalently reduced the elevated blood SOD levels in schizophrenia, but neither medication reduced the elevated plasma NO levels in schizophrenia. Low blood SOD levels at baseline predicted greater symptom improvement during treatment, and greater change in SOD was correlated with greater symptom improvement. These results suggest that both typical and atypical antipsychotic drugs may at least partially normalize abnormal free radical metabolism in schizophrenia, and some free radical parameters at baseline may predict antipsychotic responses of schizophrenic patients.

The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.

Short-Term Tropisetron Treatment and Cognitive and P50 Auditory Gating Deficits in Schizophrenia

OBJECTIVE The α7 nicotinic acetylcholine receptor (nAChR) is associated with cognitive and P50 auditory gating deficits in schizophrenia, and α7 nAChR agonists can potentially reverse these deficits. The authors examined multiple dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on cognition and P50 deficits in schizophrenia. METHOD In a randomized double-blind design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than 0.5 and were stabilized on 3-6 mg/day of risperidone were randomly assigned to receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10), or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered the Chinese-language version of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and after 10 days of treatment. RESULTS After 10 days of treatment, all three daily doses of tropisetron significantly improved overall cognitive deficits, with 10 mg showing the greatest improvement for the immediate memory index score and 20 mg for the delayed memory index score on the cognitive battery. The P50 deficits were also improved, and that improvement was significantly correlated with cognitive improvement. Two patients in the 20 mg/day group dropped out because of adverse effects, but the other dosages were well tolerated. CONCLUSIONS The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.

Plasma total antioxidant status and cognitive impairments in schizophrenia

Oxidative stress-induced damage to neurons may contribute to cognitive deficits during aging and in neurodegenerative disorders. Schizophrenia has a range of cognitive deficits that may evolve from oxidative stress, and this study examines this association of oxidative stress with cognitive deficits in schizophrenia. We recruited 296 chronic schizophrenia patients and 181 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma total antioxidant status (TAS) in both groups. Schizophrenia symptoms were assessed using the positive and negative syndrome scale (PANSS). Our results showed that TAS levels were significantly lower in patients than controls (179.6 ± 81.0 U/ml vs. 194.8 ± 46.0 U/ml, p<0.05). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.001) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenia patients than normal controls. For the patients, TAS was inversely associated with some domains of cognitive deficits in schizophrenia, such as Attention and Immediate Memory. Our findings suggest that oxidative stress may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment.

Nicotine dependence and serum BDNF levels in male patients with schizophrenia

ObjectiveSchizophrenia is associated with a significantly high prevalence of smoking. Upregulation of neurotrophins by nicotine is well established. Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The purposes of this study were to compare BDNF levels in smokers to nonsmokers with schizophrenia and examine the association between BDNF levels and psychopathological symptoms.Materials and methodsSerum BDNF levels were measured in 139 male inpatients with DSM-IV schizophrenia: 102 smokers and 37 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).ResultsThe positive PANSS symptoms were lower in smokers than in nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. BDNF levels were significantly higher in smokers than in nonsmokers (p < 0.05). Higher BDNF levels correlated with fewer negative symptoms and with smoking more cigarettes.ConclusionThe fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced upregulation of BDNF.

Brain-derived neurotrophic factor levels and its Val66Met gene polymorphism predict tardive dyskinesia treatment response to Ginkgo biloba.

BACKGROUND Tardive dyskinesia (TD) has no well-accepted treatments or known pathophysiology, but low brain-derived neurotrophic factor (BDNF) may play an important role in its pathophysiology. Ginkgo biloba (EGb-761) is a potent antioxidant that has neuroprotective effects mediated through enhancing BDNF levels. We hypothesized that treatment with EGb-761 would increase serum BDNF levels and reduce TD, particularly among schizophrenia patients who have the BDNF valine 66 to methionine (Val66Met) genotype (Val/Val). METHODS Serum BDNF levels and genotyping for the BDNF gene Val66Met polymorphism were assessed in Chinese schizophrenic patients with (n = 368) and without (n = 563) TD as well as healthy control subjects (n = 546). About half of the TD patients (n = 157) then participated in a double-blind, randomized, placebo-control 12-week treatment with 240 mg per day of EGb-761. Serum BDNF levels were measured again at posttreatment. Clinical efficacy was determined using the Abnormal Involuntary Movement Scale (AIMS). RESULTS TD patients had lower BDNF levels than the non-TD patients and healthy controls. EGb-761 treatment improved symptoms of TD and increased BDNF levels compared with placebo treatment. Moreover, the improvement of AIMS total score correlated with the increase in BDNF levels. Furthermore, improvement in the AIMS score was greatest in those with the Val/Val allele and lowest with the Met/Met allele. CONCLUSIONS The BDNF system may be implicated in the pathophysiology of TD and its improvement with antioxidant treatment. Furthermore, patients with the genetic potential for greater BDNF release (Val/Val at 66) may obtain a greater reduction in TD from EGb-761 treatment.

Reduced plasma total antioxidant status in first-episode drug-naive patients with schizophrenia

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Determination of total antioxidant status (TAS) provides an index of the sum of activities of all antioxidants. However, there have been few systematic studies to examine the relationship between TAS levels and psychopathology in first-episode and drug-naive patients with schizophrenia. TAS levels were determined in the plasma of 60 never-medicated first-episode patients with schizophrenia and 68 healthy control subjects. The schizophrenia symptomatology and the depressive symptoms were assessed by the positive and negative syndrome scale (PANSS) and the Hamilton rating scale for depression (HAMD). The results showed that TAS levels were significantly lower in first-episode patients with schizophrenia than in healthy control subjects (159.8 ± 45.8 U/ml vs 211.4 ± 46.8 U/ml, F=39.5, df=1, 126, p < 0.001). A trend toward significant inverse correlation between TAS levels and PANSS negative subscore was observed (r = 0.25, df=60, p = 0.06). Our results suggest that oxidative stress occurs in an early course of schizophrenia and may have an important role in pathogenesis and perhaps, negative symptomatology of schizophrenia.