Mustafa Bilici

Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments

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.

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder

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+/-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.

Substance use in a sample of Turkish medical students

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.

CLASSICAL AND ATYPICAL NEUROLEPTICS, AND BONE MINERAL DENSITY, IN PATIENTS WITH SCHIZOPHRENIA

There are some reports that classical neuroleptics may lead to osteoporosis or reduced bone mineral density (BMD). However, there is no adequate information about the effects of atypical neuroleptics on BMD. The aim of this study was to measure BMD in schizophrenic patients taking class -ical and atypical neuroleptics, compared to healthy controls. Seventy- five patients with schizophrenia (40 taking classical neuroleptics [CN], 35 taking atypical neuroleptics [AN]) and 20 healthy controls (HC) were included in the study. Spine (L1 L4) BMD was measured by dual-energy X-ray absorptiometry. ANOVA showed that BMD was higher in HC than AN and CN. In addition, there was a negative correlation between the duration of neuroleptic treatment and BMD and the duration of the illness. These findings suggest that atypical neuroleptics may be safer than the classical neuroleptics in terms of reduced BMD.

Sleep quality and immune functions in rheumatoid arthritis patients with and without major depression.

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 influence of olanzapine on immune cells in patients with schizophrenia

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.

Effects of antidepressant treatments on polymorphonuclear elastase levels in patients with depression.

BACKGROUND 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 Delta PMNE levels and Delta HDRS 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.

Isokinetic Muscle Performance in Major Depressive Disorder: Alterations by Antidepressant Therapy

The aims of this study were (i) to examine whether patients with major depressive disorder (MDD) differ from healthy control subjects with respect to isokinetic muscle performance (IMP) as measured by a dynamometer; (ii) to investigate the effect 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 were 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 significantly. These findings suggest that (i) MDD may be characterized by reduced IMP levels; and (ii) treatment with antidepressants may increase the IMP levels, as a state marker for depression. It was concluded that (i) isokinetic muscle performance may be used as a state marker for monitoring antidepressant drug effects on MDD; (ii) isokinetic exercise increasing IMP may be used in the treatment of depression.

Childhood abuse and neglect in adult attention-deficit/hyperactivity disorder

ABSTRACT Objective: Although it has been suggested that attention-deficit/hyperactivity disorder (ADHD) is common in children who were abused and that ADHD can be a risk factor for abuse itself, there are very few studies which investigated whether adult ADHD is associated with childhood abuse and neglect. The aim of this study was to fill this gap in the literature. Method: Seventy adults with DSM-IV ADHD diagnosis and 70 healthy control subjects were included in the study. We used Adult ADHD Self Rating Scale (ASRS) and Wender Utah Rating Scale (WURS) to support the diagnosis. All subjects were assessed using Childhood Trauma Questionnaire (CTQ), Adverse Childhood Experiences (ACE) Scale, Post-traumatic Stress Disorder Checklist (PCL), Dissociative Experiences Scale (DES), and Symptom Checklist-90-Revised. Results: ADHD subjects had higher ASRS inattentiveness, hyperactivity/impulsivity, WURS, and Symptoms Checklist-90 (SCL-90) General Symptom Index scores than controls. ADHD group also had higher PCL, DES and ACE scores. In CTQ, ADHD subjects had higher emotional abuse and neglect scores than control subjects. ASRS and WURS scores were correlated with PCL, ACE, CTQ Emotional Abuse, and DES scores; WURS score was also correlated with CTQ Physical Abuse and Neglect scores. Regression analysis indicated that general level of psychopathology was most significantly associated with DES and PCL scores. Conclusions: Results suggested that ADHD cases were more commonly exposed to emotional abuse and neglect. They had significantly more dissociative experiences and reported Post-traumatic Stress Disorder (PTSD) symptoms more frequently. The results pointed to the importance of childhood traumatic and adverse experiences in adults with ADHD.

Electroencephalography Spectral Power Density in First-Episode Mania: A Comparative Study with Subsequent Remission Period

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.