Asli Sarandol

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.

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.

Effects of second generation antipsychotics on leptin and ghrelin.

BACKGROUND Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. METHOD 112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. RESULTS When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0). CONCLUSION The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.

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 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.

Hyperprolactinemia and possibly related development of prolactinoma during amisulpride treatment; three cases

Abstract Schizophrenia is a chronic and debilitating psychotic mental disorder that affects about 1% of the worlds population. Antipsychotic drugs are the mainstay of treatment in schizophrenia. Hyperprolactinemia, which is a common side effect of typical antipsychotics, is also associated with the use of some of the newer atypical agents. Antipsychotics may enhance prolactinoma growth as manifested by an increase in serum prolactin concentration. Prolactin-secreting pituitary adenomas possibly related with antipsychotics have been described in the literature. To our knowledge, this is the first series of cases showing a possible relation between pituitary adenomas and amisulpride treatment in patients with schizophrenia.

Androgens and sexual dysfunction in naturally and surgically menopausal women

Aim:  To evaluate the influence of surgical versus natural menopause on sexual dysfunction, and the role of androgens in that context.

A comparison of the efficacy and tolerability of reboxetine and sertraline versus venlafaxine in major depressive disorder: A randomized, open-labeled clinical trial

The aim of the study was to compare the efficacy and tolerability of the combination of reboxetine and sertraline to venlafaxine XR (extended release) in major depressive disorder (MDD). The study consisted of 40 patients with MDD, aged 18-65 years. Patients were evaluated six times during a 10-week period. Treatment was started as venlafaxine XR 75 mg/day once a day (od) or reboxetine 4 mg/day twice a day (bid)+sertraline 50 mg/day od. In the second week, venlafaxine XR was increased to 150 mg/day od and reboxetine 8 mg/day bid while sertraline was kept at the same dose. The Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness and Clinical Global Impressions-Global Improvement Scale were applied on each visit. Beginning from the second visit, both groups showed significant declines in each scale. There were no significant differences between treatment response rates. Remission rates defined as HDRS<or=10 were significantly higher in the venlafaxine XR group at visit 4 only. However, when remission was accepted as HDRS<or=7, no significant difference was observed. Side effect frequency was similar between the treatment groups. We may suggest that the reboxetine+sertraline combination is not superior to venlafaxine treatment.

The potential relationship between QTc interval prolongation and ziprasidone treatment: three cases.

QTc interval prolongation may appear as a consequence of both typical and atypical antipsychotic treatments. Ziprasidone, which is effective in treating schizophrenia, is associated with QTc prolongation. Although the prolongation of QTc with ziprasidone treatment is often pronounced, there is a scarce number of cases reported about the relationship between ziprasidone and QTc prolongation. Of the three cases presented in this case series, two cases showed values exceeding 0.50 s with ziprasidone treatment.