Emre Sarandol

Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: A 24-week follow-up study

PURPOSE Major depressive disorder (MDD) is a devastating disease that afflicts large populations and has also been accepted to be an independent risk factor for cardiovascular disease (CVD). Oxidative stress seems to play an essential role in the relationship of MDD and CVD. We aimed to determine the level of oxidative stress in patients with MDD and to investigate the effects of long-term antidepressant (AD) treatment on the oxidative-antioxidative system parameters and CVD risk factors. METHOD Fifty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 44 healthy control subjects were included in the study. Control visits of the patients were repeated 6weeks, 12weeks and 24weeks after beginning of the AD treatment. Lipid profiles, oxidation and oxidizability of apolipoprotein B-containing lipoproteins (expressed as apo B-b-MDA and apo B-Δ-MDA, respectively), levels of plasma malondialdehyde (p-MDA), total antioxidative capacity (TAOC), antioxidant molecules and antioxidant enzyme activities including paraoxonase/arylesterase, red blood cell superoxide dismutase (RBC-SOD) and glutathione peroxidase were determined during 24-week of follow-up period. RESULTS According to the results of the study, p-MDA, apo B-b-MDA and RBC-SOD activity were increased and arylesterase activity was decreased in MDD patients. Body mass index (BMI), vitamin A and total cholesterol levels in MDD patients increased after 24-weeks of AD treatment. RBC-SOD activity, TAOC, p-MDA and apo B-b-MDA levels were decreased; paraoxonase/arylesterase activities and apo B-Δ-MDA were increased at the end of 24th week. CONCLUSION Oxidative stress, demonstrated in MDD patients, was partly improved during 24weeks of AD treatment. Increase in paraoxonase/arylesterase activities and decrease in p-MDA and apo B-b-MDA levels after 24weeks seem to be beneficial for reduction of CVD risk in MDD patients. However increased BMI and apo B-Δ-MDA levels are negative cardiovascular effects of long-term AD treatment.

Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment.

Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia, which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties. Increased levels of S100 B are associated with neurodegenerative disorders, including schizophrenia. The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum S100 B level was determined to investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cell (RBC) to oxidation were determined to investigate the oxidative status and plasma vitamin E, vitamin C, serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group. Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels. S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects. S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms. The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms.

The impact of ω-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: An open-label pilot study

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids (180 mg EPA+120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.

Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol.

Abstract The purpose of this study was to investigate the individual and combined antioxidant effects of menstrual cycle phase-related alterations in blood serum oestradiol concentrations and of dietary vitamin E supplementation on exercise-induced oxidative stress and muscle performance. A group of 18 sedentary women, aged 19–35 years, were given supplements of 300 mg α-tocopherol (n=10) or placebo (n=8) daily during the course of two menstrual cycles. The subjects exercised the knee isokinetically to exhaustion after cycling submaximally at 50% maximal oxygen uptake during the menstrual and preovulatory phases of their menstrual cycles. Blood samples were taken before and after the exercise, to evaluate haematocrit, plasma lactic acid and malondialdehyde concentrations, erythrocyte antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and apolipoprotein B containing lipoprotein (non-high density lipoprotein, HDL, fraction) oxidation. Serum vitamin E, follicle stimulating hormone, luteinizing hormone and oestradiol concentrations were measured in pre-exercise blood samples. Neither vitamin E supplementation nor oestradiol concentrations influenced SOD and GPx activities or the susceptibility of the non-HDL fraction to oxidation while at rest. Plasma malondialdehyde concentration was unaffected by exercise, however significant reductions in erythrocyte SOD and GPx activities and increased susceptibility of the non-HDL fraction to oxidation were noted after exercise. Exercise-induced changes were reduced when oestradiol concentration was high in the preovulatory phase, independent of the serum vitamin E concentrations. In addition, both pre- (r=0.58, P < 0.05) and post-exercise (r=0.73, P < 0.001) GPx activities in placebo administered subjects were positively correlated with oestradiol concentrations. In conclusion, these findings suggest a better protective role of oestradiol against oxidative injury, compared to vitamin E. Exhausting muscle performance was, however, not influenced by vitamin E supplementation and/or cycle-phase related changes in oestradiol concentrations.

Oxidation of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in major depressive disorder

Major depressive disorder (MDD) is blaimed to play a role in the onset of coronary artery disease (CAD). The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation of apolipoprotein B-containing lipoproteins in patients with MDD. Oxidation of lipoproteins plays an important role in atherogenesis and the enzyme paraoxonase, has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity was suggested to predict CAD. Eighty-six patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for MDD and 36 healthy control subjects were included in the study. Serum paraoxonase and arylesterase activities were determined spectrophotometrically. Malondialdehyde (MDA) levels of apolipoprotein B-containing lipoproteins were determined before (basal) and after incubation with copper-sulphate, that yielded basal- and Delta-MDA values, respectively. Serum paraoxonase/arylesterase activities were significantly reduced in the post-treatment group compared with the pre-treatment group. Basal-MDA (MDA) level was significantly higher in the MDD group compared with the control group. Delta-MDA level of the severe MDD group was significantly higher than that of the control group. There was a positive correlation between the oxidizability of apolipoprotein B-containing lipoproteins and the severity of the disease. Total cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein B levels were significantly higher and apolipoprotein AI levels were significantly lower in the MDD group compared with those of the control group. The findings of the present study suggest that: 1) antidepressant treatment might reduce serum paraoxonase activity/mass; 2) oxidation and oxidizability of apolipoprotein B-containing lipoproteins seem to be increased in MDD.

Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment

The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation/oxidizability of apolipoprotein B-containing lipoproteins and several coronary artery disease risk factors, including homocysteine, high sensitive C-reactive protein, tumour necrosis factor-α, leptin and adiponectin in patients with schizophrenia. Oxidation of lipoproteins plays an important role in atherogenesis, and the enzyme paraoxonase has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity has been suggested to predict coronary artery disease. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum paraoxonase/arylesterase activities were determined spectrophotometrically. Malondialdehyde levels of apolipoprotein B-containing lipoproteins were determined before and after incubation with copper-sulphate, which yielded basal- and Δ-malondialdehyde values, respectively. Homocysteine and highly sensitive C-reactive protein levels were determined using a fluorescence-polarization immunoassay and immunonephelometry, respectively. Leptin and adiponectin levels were measured with radioimmunoassay and tumour necrosis factor-α was determined by enzyme linked immunosorbent assay. Serum paraoxonase and arylesterase activities were significantly lower and Δ-malondialdehyde levels were significantly higher in the schizophrenia group compared with the control group. However, there were not any significant differences in other parameters of the study between the study groups. There was a significant increase in body mass index and serum triglyceride and very low density lipoprotein cholesterol levels in the schizophrenic group after 6 weeks of treatment. These parameters were significantly increased in patients treated with atypical antipsychotics but not in patients treated with typic or long acting antipsychotics. The results of the present study suggest that patients with schizophrenia might have increased risk for coronary artery disease related to reduced serum paraoxonase activity and increased oxidizability of apolipoprotein B-containing lipoproteins.

Effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men

Although there is a general consensus concerning the lower risk for cardiovascular disease in moderate drinkers, the mechanisms responsible for the cardioprotective effect of red wine remain unknown. It has been proposed that increased serum paraoxonase activity may be a mechanism of action underlying reduced cardiovascular disease risk in moderate drinkers, since paraoxonase inhibits lipoprotein oxidation. The aim of this study was to investigate the effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men. Fourteen healthy-men were included in the study. The subjects consumed 0.375 g alcohol / kg body weight for 3 weeks. Paraoxonase and arylesterase activities were studied spectrophotometrically. Oxidizability of apolipoprotein B-containing lipoproteins were determined, after separating them with precipitation method, by incubating with copper-sulfate. Paraoxonase activity did not change, however arylesterase activity significantly decreased after red wine consumption (P < 0.01). There was a reduced susceptibility of apolipoprotein B-containing lipoproteins to copper-sulfate induced oxidation after red wine consumption (P < 0.01). Our results support that red wine protects lipoproteins against oxidation, however there was not any significant change in serum paraoxonase activity after red wine consumption.

Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features

Objective: Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and leptin have been hypothesized to be involved in the neurobiology of depression. The aim of this study was to investigate BDNF, VEGF and leptin levels in patients with severe melancholic depression. Methods: A total of 40 drug-free patients with major depressive disorder (MDD) with melancholic features and 40 healthy controls were included in the study. Demographic information, psychiatric evaluation and physical examination were documented for both groups. Serum BDNF, VEGF levels were determined by enzyme-linked immunosorbent assay and leptin with radioimmunoassay methods. The Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were applied to the patients. Results: There were no significant differences in serum BDNF, VEGF and leptin levels between the patient and control groups. There was a negative correlation between BDNF levels and the number of depressive episodes. It was noted that VEGF levels decreased with increasing severity of depression. Conclusions: These findings suggest that BDNF levels might be associated with the recurrence of depression and VEGF levels might be a determinant of the severity of depression.

Effects of various antidepressants on serum thyroid hormone levels in patients with major depressive disorder

A total of 62 patients with major depressive disorder were analyzed in the study. Patients were evaluated for 11 weeks in an open label design to investigate the differential effects of reboxetine, sertraline and venlafaxine on thyroid hormones. Serum thyrotrophin (TSH), thyroxine (T4) and free (f)T4 levels were measured before and after treatment. All groups showed significant improvement in HAM-D scores. TSH level significantly reduced and T4 level significantly increased in the reboxetine group, however TSH level significantly increased and T4 level significantly reduced in the sertraline group. Percent changes of TSH (p=0.007) and T4 (p=0.001) were significantly different between the reboxetine and sertraline groups. In the sertraline group, baseline TSH levels were correlated with response to treatment as determined by the change in HAM-D scores (p=0.03, r=0.648). There was a significant association between the percent changes in TSH values and the reduction in HAM-D scores in the reboxetine group (p=0.03, r=-0.434). In the whole study group, female patients had lower values of basal T4 compared with men (p=0.043), however percent changes of T4 did not differ between genders. In the treatment-responders significant increase in the reboxetine group and significant decrease in the sertraline group regarding the T4 values were found. We observed that various antidepressants had different effects on thyroid hormone levels and this could be attributed to the different mechanisms of actions of these antidepressants.

First-episode psychosis is associated with oxidative stress: Effects of short-term antipsychotic treatment

In the present study, our aim was to investigate the oxidative–antioxidative systems in unmedicated first‐episode psychosis (FEP) patients at the beginning and after short‐term treatment.