Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased ...mortality is cardiovascular disease (CVD). The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ.
This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190) in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day) or a placebo group (200 mg/day). In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024) and in LDL-cholesterol (p = 0.002), as well as a decrease in body fat percentage (p = 0.038). The placebo group also showed an increase in triglycerides (9.19%) and a reduction in HDL-cholesterol (4.88%). In the resveratrol group, triglycerides decreased (7.64%).
In summary, oral resveratrol in reasonably low dosages (200 mg daily) brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels.
There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD).
We compared the antioxidant ...enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (
N
=
21), manic (
N
=
32) and euthymic (
N
=
31) bipolar patients, and in chronically medicated patients with schizophrenia (
N
=
97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (
N
=
32).
Serum SOD (U/mg protein) activity was significantly increased (
p
<
0.001) in manic (7.44
±
3.88) and depressed (6.12
±
4.64) BD patients and SZ (9.48
±
4.51) when compared to either controls (1.81
±
0.63) or euthymic (2.75
±
1.09) BD patients. TBARS (mol/L) levels were significantly higher in the SZ group (4.95
±
1.56,
p
=
0.016), bipolar euthymic (6.36
±
1.46,
p
<
0.001), bipolar manic (7.54
±
1.74,
p
<
0.001), and bipolar depressed patients (5.28
±
1.54,
p
=
0.028) compared to controls (3.96
±
1.51).
Our findings show increased SOD activity in SZ, as well as in depressed and manic bipolar patients, but not in euthymic BD subjects. This suggests a dysregulation in oxidative defenses in both disorders. It is likely that such changes reflect state changes in bipolar disorder. It is possible that this is a compensatory response to the oxidative stress that occurs in the acute phase of bipolar episodes. TBARS results show increases in lipid peroxidation in mania. TBARS levels in SZ and in euthymic as well as depressed individuals with BD were higher than in controls. This suggests persistent increases in SZ, which may reflect ongoing symptomatology or treatment, and a state dependant gradient in BD, with greatest oxidative stress in mania.
These data support oxidative biology as both a key component of the pathophysiology of both BD and SZ, and the use of agents that modulate oxidative biology as a promising avenue for intervention in both disorders.
Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has ...been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders.
A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition.
In the Cox regression model, ethnicity (white) (hazard ratio HR 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05).
These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.
Abstract Schizophrenia (SZ) is a debilitating neurodevelopmental disorder that strikes at a critical period of a young person’s life. Its pathophysiology could be the result of deregulation of ...synaptic plasticity, with downstream alterations of inflammatory immune processes regulate by cytokines, impaired antioxidant defense and increased lipid peroxidation. The aim of this study was to examine serum oxidative stress markers and inflammatory cytokines in early and late phases of chronic SZ. Twenty-two patients at early stage (within first 10 years of a psychotic episode), 39 at late stage (minimum 10 years after diagnosis of SZ) and their respective matched controls were included. Each subject had 5 ml blood samples collected by venipuncture to examined thiobarbituric acid-reactive substances (TBARS), total reactive antioxidant potential (TRAP), protein carbonyl content (PCC), Interleukins 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha (TNF-alpha). TBARS, IL-6 and PCC levels were significantly higher in patients with SZ at early and late stages than in controls. There were no differences for TRAP and TNF-alpha levels in patients with SZ at early and late stages than in controls. IL-10 levels were decreased in patients at late stage and a decrease trend in early stage was found. Results provided evidence consistent with comparable biological markers across chronic SZ. The concept of biochemical staging proposed by others for bipolar disorder is not seen in this cohort of patients with SZ, at least for cytokines and oxidative stress markers. Our findings reinforce the need of assessment of individuals in ultra high risk to develop psychosis and first-episode population.
There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of ...neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (
n
=
27), typical (
n
=
14), and other atypical antipsychotics (
n
=
19), 30 euthymic BD patients, and 26 healthy control had 5
ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (
p
<
0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.
Schizophrenia (SZ) is associated with psychotic experiences and cognitive deficits. Therefore, cognitive function is one of the most critical determinants of quality of life in this pathology. ...Resveratrol has been related to neuroprotective action, but there are no studies evaluating resveratrol in SZ. The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with SZ.
This is a 1-month randomized, double-blind, and controlled trial (NCT 02062190), in which 19 men with diagnosis of SZ, aged 18-65 years, were assigned to a resveratrol supplementation group (200 mg) or placebo group (200 mg), with a 1-month follow-up. Applying a series of cognitive tests assessed neuropsychology performance (Hopkins Verbal Learning Test, Stroop Color and Word Test, and Weschler Adult Intelligence Scale) and Brief Psychiatric Rating Scale assessed psychopathology severity.
There were no significant improvement in neuropsychology performance (episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility) and psychopathology severity after 1 month of resveratrol supplementation (
> 0.05).
In conclusion, we have shown that 1 month of a resveratrol supplementation (200 mg/day) did not improve episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility as compared with placebo in patients with SZ.
Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment ...of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia.
In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS).
Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size ES = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed.
Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients.
clinicaltrials.gov Identifier: NCT00757978.
Schizophrenia is a severe mental disorder associated with important physical (obesity and low motor functional capacity) and metabolic (diabetes and cardiovascular diseases) changes that contribute ...to a more sedentary lifestyle and a low quality of life.
The study aimed to measure the effect of two different protocols of physical exercise aerobic intervention (AI) versus functional intervention (FI) on lifestyle in schizophrenia compared with healthy sedentary subjects.
A controlled clinical trial involving patients diagnosed with schizophrenia from two different locations Hospital de Clinicas de Porto Alegre (HCPA) and Centro de Atenção Psicosocial (CAPS) in the city of Camaquã was carried out. The patients undertook two different exercise protocols (IA: 5-min warm-up of comfortable intensity; 45 min of aerobic exercise of increasing intensity using any of the three modalities-a stationary bicycle, a treadmill, or an elliptical trainer; and 10 min of global stretching of large muscle groups; and FI: a 5 min warm-up with a stationary walk; 15 min of muscle and joint mobility exercises; 25 min of global muscle resistance exercises; and 15 min of breathing body awareness work) twice a week for 12 weeks and were compared with physically inactive healthy controls. Clinical symptoms (BPRS), life quality (SF-36), and physical activity levels (SIMPAQ) were evaluated. The significance level was
≤ 0.05.
The trial involved 38 individuals, of which 24 from each group performed the AI, and 14 from each group underwent the FI. This division of interventions was not randomized but was instead decided upon for convenience. The cases showed significant improvements in quality of life and lifestyle, but these differences were greater in the healthy controls. Both interventions were very beneficial, with the functional intervention tending to be more effective in the cases and the aerobic intervention more effective in the controls.
Supervised physical activity improved life quality and reduced sedentary lifestyle in adults with schizophrenia.
The present study sought to assess biomarkers of inflammation in stable patients with schizophrenia (SZ) on clozapine therapy. We recruited 60 outpatients with SZ and 60 healthy controls, matched for ...sex and age. Compared with controls, patients had significantly increased concentrations of interleukin-6 and tumor necrosis factor-α. Interestingly, patients on simvastatin had lower interleukin-6 levels compared with patients not on simvastatin and controls. This study corroborated previous evidence for increased inflammatory biomarkers in SZ and detected a potential anti-inflammatory action of simvastatin in patients with a clinical diagnosis of SZ on clozapine therapy.
Abstract Brain Derived Neurotrophic Factor (BDNF) has been associated with the pathophysiology of schizophrenia (SCZ). However, it remains unclear whether alterations in BDNF observed in patients ...with SCZ are a core part of disease neurobiology or a consequence of treatment. In this manuscript we review existing knowledge relating the function of BDNF to synaptic transmission and neural plasticity and the relationship between BDNF and both pharmacological and non-pharmacological treatments for SCZ. With regards to synaptic transmission, exposure to BDNF or lack of this neurotrophin results in alteration to both excitatory and inhibitory synapses. Many authors have also evaluated the effects of both pharmacological and non-pharmacological treatments for SCZ in BDNF and despite some controversial results, it seems that medicated and non-medicated patients present with lower levels of BDNF when compared to controls. Further data suggests that typical antipsychotics may decrease BDNF expression whereas mixed results have been obtained with atypical antipsychotics. The authors found few studies reporting changes in BDNF after non-pharmacological treatments for SCZ, so the existing evidence in this area is limited. Although the study of BDNF provides some new insights into understanding of the pathophysiology and treatment of SCZ, additional work in this area is needed.
PDF
