Shu Ping Tan

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.

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.

Gender difference in association of cognition with BDNF in chronic schizophrenia

While numerous studies have reported that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia, very few studies have explored its association with cognitive impairment or gender differences in schizophrenia which we explored. We compared gender differences in 248 chronic schizophrenic patients (male/female=185/63) to 188 healthy controls (male/female=98/90) on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that schizophrenic patients performed worse than normals on most of the cognitive tasks, and male patients had significantly lower immediate memory and delayed memory scores than female patients. BDNF levels were significantly lower in patients than controls, and male patients had significantly lower BDNF levels than female patients. For the patients, BDNF was positively associated with immediate memory and the RBANS total score. Furthermore, these associations were only observed in female not male patients. Among healthy controls, no gender difference was observed in cognitive domains and BDNF levels, or in the association between BDNF and cognition. Our results suggest gender differences in cognitive impairments, BDNF levels and their association in chronic patients with schizophrenia. However, the findings should be regarded as preliminary due to the cross-sectional design and our chronic patients, which need replication in a first-episode and drug naïve patients using a longitudinal study.

Interaction of BDNF with cytokines in chronic schizophrenia.

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.

Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition

ObjectiveA substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia.Materials and methodsSerum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA).ResultsTNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (p < 0.01). Correlation analysis revealed a significant negative correlation between the TNFα levels and the PANSS total score (p < 0.01). Additionally, TNFα levels were significantly negatively correlated with scores on general psychopathology (p < 0.01), positive (p < 0.05) and cognitive subscales (p < 0.05). Stepwise multiple regression analysis identified TNFα levels as a significant predictor of scores on the general psychopathology subscale of the PANSS.ConclusionThe significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Cognition impairment in schizophrenia patients with tardive dyskinesia: association with plasma superoxide dismutase activity.

Long-term antipsychotic treatment for schizophrenia is often associated with the emergence of tardive dyskinesia (TD), and TD presence is also accompanied by more severe cognitive impairment. Oxidative stress-induced damage may be involved in the development of TD and contribute to cognitive deficits in schizophrenia. We examined the role of oxidative stress in relation to TD and cognitive deficits in schizophrenia using plasma manganese superoxide dismutase (MnSOD) as a biomarker. We recruited 83 male chronic patients with (n=32) and without TD (n=51) meeting DSM-IV criteria for schizophrenia, and 58 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and MnSOD activity for all subjects. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patients. MnSOD activity was lower in patients with TD than non-TD, and either TD or non-TD group had lower MnSOD levels than controls (all p<0.05). Patients with TD had lower RBANS total (p<0.05) and Visuospatial/Constructional subscale scores than non-TD patients (p<0.01), and either TD or non-TD group scored lower than the controls on all RBANS subscales (all p<0.001) except for the Visuospatial/Constructional index. Multiple regression analysis showed that in either TD or non-TD group, MnSOD was an independent contributor to the RBANS total score (both p<0.05). These findings suggest that TD patients suffered oxidative stress and cognition impairment at a more severe level than non-TD patients. Oxidative stress might serve as a functionally linking node between TD development and cognition dysfunction in schizophrenia.

The effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia and the follow-up study.

In this double-blind, randomized controlled study, we assessed the therapeutic effects of high-frequency left dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia. For the study, 117 patients with prominent negative symptoms were randomized to a 20-day course of either active rTMS applied to the left DLPFC (n = 78) or sham rTMS (n = 39). The primary outcome measures were the Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Secondary outcomes included the Clinical Global Impressions Scale (CGI) and the Udvalg for Kliniske Under sogelser (UKU) Side Effect Rating Scale. We found that treatment with high-frequency rTMS for 6 weeks significantly improved negative symptoms in the active group as compared to the sham group. However, active rTMS was not correlated with significant improvement in the CGI severity of illness scale (CGI-S). The improvement of negative symptoms persisted to the 24-week follow-up assessment. These results indicate that there is a lasting beneficial effect of rTMS on negative symptoms in absence of decrease in CGI scores. We conclude that rTMS may serve as a relatively noninvasive treatment that alleviates negative symptoms in patients with schizophrenia.

BDNF polymorphisms are associated with schizophrenia onset and positive symptoms.

Numerous studies have showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis and pathophysiology of schizophrenia. The purposes of this study were to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and the psychopathological symptoms in patients with schizophrenia in a Han Chinese population. Four polymorphisms (rs6265, rs12273539, rs10835210 and rs2030324) of the BDNF gene were analyzed in a case-control study of 1887 Han Chinese individuals (844 patients and 1043 controls). We assessed 825 patients for psychopathology using the Positive and Negative Syndrome Scale. In single marker analyses the BDNF rs10835210 mutant A allele was significantly associated with schizophrenia. Haplotype analyses revealed higher frequencies of haplotypes containing the mutant A allele of the rs10835210 in schizophrenia than controls. We also found that this polymorphism rs10835210 was associated with positive symptoms, and the patients carrying the mutational allele A showed more positive symptoms. These findings suggest the role of these BDNF gene variants in both susceptibility to schizophrenia and in clinical symptom severity.

Increased IL-3 serum levels in chronic patients with schizophrenia: Associated with psychopathology

Schizophrenia is associated with the inflammation-related pathways, including aberrant cytokines levels. In this study, we examined the association of serum IL-3 levels with psychopahological symtoms in chronic schizophrenia. Serum IL-3 levels were assessed in 42 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Our results showed that IL-3 levels were significantly increased in patients with chronic schizophrenia compared to healthy control subjects. Correlation analysis revealed a significant positive correlation between the IL-3 levels and the PANSS general subscore. Moreover, IL-3 levels were significantly positively correlated with depressive subscore. Our results suggested that IL-3 related pathway is associated with psychopathology of schizophrenia patients.

Effects of cigarette smoking and alcohol use on neurocognition and BDNF levels in a Chinese population.

ObjectiveFew studies have examined the potential interactive effect of both smoking and drinking on cognition. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognition. This is the first study to examine the neurocognitive consequences of cigarette smoking combined with chronic alcohol consumption and their relationship to serum BDNF levels in a Chinese Han population.Materials and methodsWe recruited 191 healthy male subjects, including 47 isolated smokers, 31 isolated chronic alcohol users, 58 combined smokers and chronic alcohol users, and 55 non-smokers and non-alcohol users. We then compared the repeatable battery for the assessment of neuropsychological status (RBANS) scores and serum BDNF levels in these four groups.ResultsWhen compared to the non-smoking + non-alcohol-using group, the smoking group performed worse on immediate memory, attention, language, and RBANS total score. There were no significant differences in the RBANS scores between the alcohol-using group and non-smoking + non-alcohol-using group, or between the smoking group and smoking + alcohol-using group. We did not find an association between BDNF and smoking or drinking status or between BDNF and cognitive performance. In the smoking group, there was a significant correlation between BDNF and carbon monoxide concentration, and between BDNF and the Fagerstrom Test for Nicotine Dependence (FTND) total score.ConclusionsOur results suggest that smoking is associated with cognitive decline, but not with BDNF levels in a normal population. However, smoking severity is positively associated with BDNF levels. Concomitant alcohol use does not worsen the cognitive decline caused by smoking.