Fu De Yang

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.

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.

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.

Decreased interleukin-10 serum levels in first-episode drug-naïve schizophrenia: Relationship to psychopathology

Many lines of findings support the hypothesis of the inflammation-related pathways in the multifactorial pathogenesis of schizophrenia (SZ). Interleukin-10 (IL-10), a potential anti-inflammatory cytokine, was found to be altered in chronic patients with SZ. The aim of this study was to assess the serum levels of IL-10 in first-episode and drug-naïve (FEDN) patients with SZ and its relationships with the psychopathological parameters. Serum IL-10 levels were analyzed using established procedures in 128 FEDN patients with SZ and 62 healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive factor derived from the five factor model of the PANSS. Compared to the healthy controls, the patients exhibited a significant decrease in IL-10 levels. Serum IL-10 was inversely correlated with the PANSS negative symptom, as well as with the PANSS cognitive factor subscores in patients. Our results suggested that decreased IL-10 may be implicated in the negative symptom and cognitive impairment at the acute stage of schizophrenia episode.

Elevated interleukin-18 serum levels in chronic schizophrenia: Association with psychopathology

BACKGROUND Schizophrenia is associated with various abnormalities in the immune system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the clinical significance of serum IL-18 levels in various stages of schizophrenia. METHODS We measured serum IL-18 levels using a sandwich enzyme-linked immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia, 79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). RESULTS The chronic patients had significantly greater serum IL-18 levels than both first-episode patients and controls. Serum IL-18 was also positively correlated with the PANSS general psychopathology subscore in chronic schizophrenic patients. CONCLUSIONS Our results showed elevated IL-18 pathway activity may be involved in the psychopathology of schizophrenia.

Thoracoscopic enucleation of esophageal leiomyoma: a retrospective study on 40 cases

Esophageal leiomyoma is the most common benign esophageal tumor. Thoracoscopic enucleation is currently a preferred approach to most of these lesions. We present our experiences of enucleation of these tumors using thoracoscopic approach. A retrospective review of 40 patients who underwent enucleation of esophageal leiomyoma from 1997 to 2007 in our institute was conducted. Presenting symptoms, operative approach, tumor size, tumor shape, outcomes, and indication for this approach were analyzed. Forty patients were identified. Postoperative histopathology confirmed the leiomyoma in all patients. The thoracoscopic enucleation was completed in 34 cases, and the operation was converted to open procedure in six cases. Reasons for conversion included too small tumors to be visualized in two cases, thoracic cavity adhesion in one case, and the too large tumors in three cases. The median operating time was 70 min (50 to 210 min). Mean tumor size was 3.7 cm (0.5-10 cm). There were no major postoperative complications. Symptoms especially dysphasia were relieved postoperatively. Short- and long-term follow-up was satisfactory with none of the patients having tumor recurrences or other problems. Thoracoscopic enucleation of esophageal leiomyoma is technically safe and effective. It is currently the best choice for management of esophageal leiomyoma 1 to 5 cm in diameter. It can also be tried on a tumor larger than 5 cm, although the possibility of conversion to thoracotomy increases along with tumor growing and surrounding the esophagus.

The interplay between BDNF and oxidative stress in chronic schizophrenia

Neurodegenerative processes may be involved in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin and oxidative stress (OS) may be critical for several pathological manifestations of neurodegenerative disorders. Accumulating evidence suggests that both BDNF and OS may be involved in the pathophysiology of schizophrenia. However, the possible interaction between BDNF and OS has been under-investigated. Serum BDNF, plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 164 chronic medicated schizophrenia and 50 healthy controls. Schizophrenic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive and depressive factors derived from the five factor model of the PANSS. Compared to the control group, the patients exhibited a significant decrease in BDNF levels, in the activities of SOD and GSH-Px but a significant increase in MDA levels. In patients, but not in controls, we observed a significant negative correlation between BDNF and SOD. Furthermore, the interaction between BDNF and CAT was associated with the PANSS cognitive factor, and the interaction between BDNF and GSH-Px with the PANSS depressive factor. Both decreased BDNF levels and OS may be implicated in the pathophysiology of chronic schizophrenia. Their inverse association only in the schizophrenia group may reflect a pathological mechanism involving an interaction of oxidative damage and neurotrophin dysfunction. Moreover, OS may interact with the BDNF system to influence the clinical symptoms and cognitive impairment in schizophrenia, which is line with the neurodevelopmental hypothesis of schizophrenia.

Thioredoxin, a novel oxidative stress marker and cognitive performance in chronic and medicated schizophrenia versus healthy controls

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. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker has recently been found to be involved in pathogenesis and psychopathology of schizophrenia. The aim of this study was to examine the association of TRX with cognitive deficits in schizophrenia. We recruited 45 chronic schizophrenic patients and 66 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum TRX in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found no significant difference in TRX levels between patients and healthy controls. Cognitive scores on the RBANS and four 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, TRX was inversely associated with the Attention domain of cognitive deficits in schizophrenia; however, TRX was positively associated with Attention in controls. The significantly lower TRX levels in attention impaired schizophrenia compared to controls suggest that oxidative stress may be involved in the cognitive impairment, especially attention in schizophrenia. The differential association of TRX and cognitive performance in schizophrenia and controls may be related to the impaired oxidative stress status of schizophrenia patients.

Interleukin 18 and cognitive impairment in first episode and drug naïve schizophrenia versus healthy controls

Alterations in the inflammatory and immune systems have been documented to occur from the earliest stages of schizophrenia, and have been associated with neurodevelopmental changes. Cognitive impairment is a core feature in the pathology of schizophrenia, and recent studies showed a significant increase in serum IL-18 in schizophrenia, and a putative role of IL-18 in neuroprogression and thus neurocognitive defects. The purpose of this study was to examine the association of IL-18 with cognitive deficits in schizophrenia. We recruited 77 first episode and drug naïve schizophrenic patients and 75 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-18 in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found that IL-18 levels were non-significantly higher in patients than controls (206.0±92.9 pg/ml vs 193.2±41.8 pg/ml, p=0.28). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.05) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, IL-18 was positively associated with the Visuospatial/Constructional domain of cognitive deficits in schizophrenia. Our findings suggest that cognitive deficits occur during the acute stage of a schizophrenic episode, and IL-18 may be involved in Visuospatial/Constructional deficits of these patients.

Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes.

The high prevalence of smoking in schizophrenia of European background may be related to smokings reducing clinical symptoms and medication side effects. Because smoking prevalence and its associations with clinical phenotypes are less well characterized in Chinese than European patients with schizophrenia, we assessed these smoking behaviors using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND) in 776 Chinese male schizophrenia and 560 control subjects. Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). We found that the schizophrenia patients had a higher lifetime incidence of smoking (79% vs 63%), were more likely to be heavy smokers (61% vs 31%), and had lower smoking cessation rates (4% vs 9%) (all p<0.0001) than controls. Among the schizophrenia patients smoking prevalence increased with age, with the largest difference from controls in the age cohort of 55–75 years: 75% vs 46% (p<0.0001). Among the schizophrenia smokers 73% started to smoke before the onset of their illness by an average of 7.6 years. The patients with schizophrenia who were current smokers scored significantly lower on the PANSS negative symptom subscore (p<0.005), and on the SAES symptom scale (p<0.04; Bonferroni corrected p>0.05) than the non-smoking patients. These results suggest that Chinese males with schizophrenia smoke more frequently than the general population. Further, smokers with schizophrenia may display fewer negative symptoms and possibly less parkinsonism than non-smokers with schizophrenia.