Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2003
In vitro and preclinical studies show that biochemical and behavioral effects of olanzapine are q... more In vitro and preclinical studies show that biochemical and behavioral effects of olanzapine are quite similar to those of clozapine. In recent years, some cases of reported agranulocytosis due to olanzapine have been published. However, none of these studies compared the hematological and immune parameters before and after treatment. The present study is aimed at investigating the influence of olanzapine on the immune cell parameters by comparing these before and in the third month of olanzapine treatment in patients of schizophrenia. Twenty patients who were diagnosed as schizophrenic depending on the DSM-IV diagnostic criteria were included in the study. The immune parameters of patients were compared by measuring them before the treatment and 3 months after treatment. Immune parameters were analyzed by using flow-cytometry equipment labeled Coulter Epics Elite ESP. The positivity of cell-surface antibody was evaluated as percentage. The rates of CD8 in the third month of the treatment were considerably increased relative to pretreatment. Furthermore, rates of CD4/CD8 were significantly decreased in the third month of the treatment relative to before treatment. These findings suggest that immune impairment may occur during olanzapine treatment in patients with schizophrenia.
The purpose of this study was to determine the discriminative factors between rheumatoid arthriti... more The purpose of this study was to determine the discriminative factors between rheumatoid arthritis (RA) patients with and without major depression (MD). We assessed subjective sleep quality, pain, and cell-mediated immune functions in RA patients with (n = 20) and without (n = 20) MD by using Pittsburgh Sleep Quality Index (PSQI), visual analogue scale (VAS), and fluorescein isothiocyanat (FITC) labeled CD3, CD4, CD8, CDI9, CD45, CD56, and HLADR T monoclonal antibodies by flow cytometry. We found that the RA patients with MD had significantly higher pain level, poorer sleep equality, higher HDRS points, and higher HLADR T cell level than those without MD; and that these variables are discriminant factors between patient groups. These findings suggest that the RA patients with MD may be differentiated from those without MD by using VAS, PSQI, and HLADR levels; that these variables correctly classify the depressed and non depressed groups up to an accuracy level of 96.8%.
The Israel journal of psychiatry and related sciences, 1997
Several cytogenetic surveys and literature reviews have suggested a possible association between ... more Several cytogenetic surveys and literature reviews have suggested a possible association between Klinefelter's syndrome and bipolar illness. We describe a manic patient with Klinefelter's syndrome who was treated successfully with lithium. Our patient represents the 32nd reported case of bipolar disorder in an individual with a known chromosomal abnormality, the 15th with Klinefelter's syndrome, and the 11th with a karyotype of 47XXY.
ABSTRACT Introduction: Our aim in this study was to investigate spectral power density (PSD) in f... more ABSTRACT Introduction: Our aim in this study was to investigate spectral power density (PSD) in first-episode mania and subsequent remission period and to evaluate their difference. Methods: Sixty-nine consecutive cases referring to our hospital within the previous 1 year, who were evaluated as bipolar disorder manic episode according to The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) at the first episode and had the informed consent form signed by first degree relatives, were included in this study. Exclusion criteria included having previous depressive episode, using drugs which could influence electroencephalographic activity before electroencephalography (EEG), and having previous neurological disease, particularly epilepsy, head trauma, and/or loss of consciousness. EEG records were obtained using a digital device in 16 channels; 23 surface electrodes were placed according to the International 10–20 system. Spectral power density (dbμV/Hz) of EEG signal provided information on the power carried out by EEG waves in defined frequancy range per unit frequency in the present study. Results: A peak power value detected on the right with FP2P4 and on the left with F7T3 electrodes were found to be higher in the manic episode than in the remission period (p=0.018 and 0.025). In the remission period, in cases with psychotic symptoms during the manic period, F4C4 peak power value was found to be lower than that in cases with no psychotic findings during the manic period (p=0.027). There was no relation was found between YMRS scores and peak power scores. Conclusion: Electrophysiological corollary of mood episode is present from the onset of the disease, and it differs between the manic and remission periods of bipolar disorder. In the remission period, peak power values of PSD distinguish cases with psychotic findings from cases without psychotic findings when they were manic.
The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) ... more The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) dier from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the eect of subchronic treatment on the IMP in depressed patients. Thirty-eight patients with MDD, and 41 sex-and age-matched healthy controls participated in this study. The severity of depression and anxiety levels was evaluated by the Hamilton Depression and Anxiety Scales. Quadriceps and hamstring IMPs were determined by using an isokinetic dynamometer before and after subchronic antidepressant treatment. The patients had lower IMP levels than healthy controls. After treatment for three months with selective serotonin reuptake inhibitors, the IMP levels increased signi®cantly. These ®ndings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, being a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug eects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2004
Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD... more Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. Methods: Patients with a primary DSM-IV diagnosis of ADHD (N = 400; 72 girls, 328 boys, mean age = 9.61 F 1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n = 202) (150 mg/day) or placebo (n = 198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels. D
We have previously reported that severe depression is associated with immunological and inflammat... more We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. Methods: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). Results: There was a positive correlation between DPMNE levels and DHDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. Conclusion: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. Clinical implication and limitations: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression.
Background: Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. The... more Background: Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. Methods: The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and / or in red blood cells. Results: Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. Conclusion: These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. Clinical implication and limitation: AEAs might be used for monitoring SSRIs effects.
This study identifies the prevalence of smoking, alcohol, and illicit drug use in a sample of Tur... more This study identifies the prevalence of smoking, alcohol, and illicit drug use in a sample of Turkish medical students. Information about substance use was obtained from 304 first-year, and 143 sixth-year medical students from three different medical schools in Turkey. Nearly half of the students (53.9%) were non-drinkers. Risky alcohol use was 7.4%. Lifetime smoking prevalence was 39.9 and 26.4% of the junior and 44.1% of the senior medical students (mean consumption of 13.9 and 15.5 cigarettes a day, respectively) reported regular smoking. Nicotine dependence was present in 3.1%. Only 4% of the students reported using illicit drugs (cannabis, ecstasy, cocaine) at least once in their lifetime. The mean ages of first use of cigarettes, alcohol and illicit drugs were earlier for junior medical students than senior students. Of the students, 25.5% had anxiety and 36.8% had depression scores in the clinically significant range. Our results suggest that although Turkish medical students are not at a high risk of substance abuse it should not be underestimated, and the risk factors as well as the protective factors must be identified in nation-wide studies.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2003
In vitro and preclinical studies show that biochemical and behavioral effects of olanzapine are q... more In vitro and preclinical studies show that biochemical and behavioral effects of olanzapine are quite similar to those of clozapine. In recent years, some cases of reported agranulocytosis due to olanzapine have been published. However, none of these studies compared the hematological and immune parameters before and after treatment. The present study is aimed at investigating the influence of olanzapine on the immune cell parameters by comparing these before and in the third month of olanzapine treatment in patients of schizophrenia. Twenty patients who were diagnosed as schizophrenic depending on the DSM-IV diagnostic criteria were included in the study. The immune parameters of patients were compared by measuring them before the treatment and 3 months after treatment. Immune parameters were analyzed by using flow-cytometry equipment labeled Coulter Epics Elite ESP. The positivity of cell-surface antibody was evaluated as percentage. The rates of CD8 in the third month of the treatment were considerably increased relative to pretreatment. Furthermore, rates of CD4/CD8 were significantly decreased in the third month of the treatment relative to before treatment. These findings suggest that immune impairment may occur during olanzapine treatment in patients with schizophrenia.
The purpose of this study was to determine the discriminative factors between rheumatoid arthriti... more The purpose of this study was to determine the discriminative factors between rheumatoid arthritis (RA) patients with and without major depression (MD). We assessed subjective sleep quality, pain, and cell-mediated immune functions in RA patients with (n = 20) and without (n = 20) MD by using Pittsburgh Sleep Quality Index (PSQI), visual analogue scale (VAS), and fluorescein isothiocyanat (FITC) labeled CD3, CD4, CD8, CDI9, CD45, CD56, and HLADR T monoclonal antibodies by flow cytometry. We found that the RA patients with MD had significantly higher pain level, poorer sleep equality, higher HDRS points, and higher HLADR T cell level than those without MD; and that these variables are discriminant factors between patient groups. These findings suggest that the RA patients with MD may be differentiated from those without MD by using VAS, PSQI, and HLADR levels; that these variables correctly classify the depressed and non depressed groups up to an accuracy level of 96.8%.
The Israel journal of psychiatry and related sciences, 1997
Several cytogenetic surveys and literature reviews have suggested a possible association between ... more Several cytogenetic surveys and literature reviews have suggested a possible association between Klinefelter's syndrome and bipolar illness. We describe a manic patient with Klinefelter's syndrome who was treated successfully with lithium. Our patient represents the 32nd reported case of bipolar disorder in an individual with a known chromosomal abnormality, the 15th with Klinefelter's syndrome, and the 11th with a karyotype of 47XXY.
ABSTRACT Introduction: Our aim in this study was to investigate spectral power density (PSD) in f... more ABSTRACT Introduction: Our aim in this study was to investigate spectral power density (PSD) in first-episode mania and subsequent remission period and to evaluate their difference. Methods: Sixty-nine consecutive cases referring to our hospital within the previous 1 year, who were evaluated as bipolar disorder manic episode according to The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) at the first episode and had the informed consent form signed by first degree relatives, were included in this study. Exclusion criteria included having previous depressive episode, using drugs which could influence electroencephalographic activity before electroencephalography (EEG), and having previous neurological disease, particularly epilepsy, head trauma, and/or loss of consciousness. EEG records were obtained using a digital device in 16 channels; 23 surface electrodes were placed according to the International 10–20 system. Spectral power density (dbμV/Hz) of EEG signal provided information on the power carried out by EEG waves in defined frequancy range per unit frequency in the present study. Results: A peak power value detected on the right with FP2P4 and on the left with F7T3 electrodes were found to be higher in the manic episode than in the remission period (p=0.018 and 0.025). In the remission period, in cases with psychotic symptoms during the manic period, F4C4 peak power value was found to be lower than that in cases with no psychotic findings during the manic period (p=0.027). There was no relation was found between YMRS scores and peak power scores. Conclusion: Electrophysiological corollary of mood episode is present from the onset of the disease, and it differs between the manic and remission periods of bipolar disorder. In the remission period, peak power values of PSD distinguish cases with psychotic findings from cases without psychotic findings when they were manic.
The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) ... more The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) dier from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the eect of subchronic treatment on the IMP in depressed patients. Thirty-eight patients with MDD, and 41 sex-and age-matched healthy controls participated in this study. The severity of depression and anxiety levels was evaluated by the Hamilton Depression and Anxiety Scales. Quadriceps and hamstring IMPs were determined by using an isokinetic dynamometer before and after subchronic antidepressant treatment. The patients had lower IMP levels than healthy controls. After treatment for three months with selective serotonin reuptake inhibitors, the IMP levels increased signi®cantly. These ®ndings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, being a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug eects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2004
Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD... more Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. Methods: Patients with a primary DSM-IV diagnosis of ADHD (N = 400; 72 girls, 328 boys, mean age = 9.61 F 1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n = 202) (150 mg/day) or placebo (n = 198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels. D
We have previously reported that severe depression is associated with immunological and inflammat... more We have previously reported that severe depression is associated with immunological and inflammatory alterations and these alterations may be showed easily by polymorphonuclear elastase (PMNE) measurements. The purpose of the present study is to show how PMN elastase levels change before and after antidepressant treatment. Methods: Fifty-five patients with depression (40 with major depression [MD], 15 with dysthymic disorder [DD]) were included in the study. Blood samples were drawn prior to drug treatment, and 3 months after the treatment. Severity of depression was measured by 24-item Hamilton depression rating scale (HDRS). Results: There was a positive correlation between DPMNE levels and DHDRS in patients with MD, but not in patients with DD. Twenty-eight patients were given moclobemide, and 27 patients were given imipramine. It was seen that PMN elastase levels were significantly reduced after 3-month antidepressant treatment period only in patients with MD. Conclusion: These findings suggest that PMNE activity is a state dependent parameter and improvement of depressive symptoms due to antidepressant treatment may lead to decrement of PMNE levels. Clinical implication and limitations: PMN elastase measurements may be used as a sensitive biological marker to follow the time-course of the disease activity in patients with major depression.
Background: Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. The... more Background: Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. Methods: The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and / or in red blood cells. Results: Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. Conclusion: These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. Clinical implication and limitation: AEAs might be used for monitoring SSRIs effects.
This study identifies the prevalence of smoking, alcohol, and illicit drug use in a sample of Tur... more This study identifies the prevalence of smoking, alcohol, and illicit drug use in a sample of Turkish medical students. Information about substance use was obtained from 304 first-year, and 143 sixth-year medical students from three different medical schools in Turkey. Nearly half of the students (53.9%) were non-drinkers. Risky alcohol use was 7.4%. Lifetime smoking prevalence was 39.9 and 26.4% of the junior and 44.1% of the senior medical students (mean consumption of 13.9 and 15.5 cigarettes a day, respectively) reported regular smoking. Nicotine dependence was present in 3.1%. Only 4% of the students reported using illicit drugs (cannabis, ecstasy, cocaine) at least once in their lifetime. The mean ages of first use of cigarettes, alcohol and illicit drugs were earlier for junior medical students than senior students. Of the students, 25.5% had anxiety and 36.8% had depression scores in the clinically significant range. Our results suggest that although Turkish medical students are not at a high risk of substance abuse it should not be underestimated, and the risk factors as well as the protective factors must be identified in nation-wide studies.
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Papers by M. Bilici