Age-related changes of superoxide dismutase activity in patients with schizophrenia.

Background/Aim: Superoxide dismutase (SOD) is the critical enzyme in the detoxification of superoxide radicals because those are the first species produced in the majority of biological free radical producing reactions. Inconsistent data are present about SOD activity in patients with schizophrenia. Numerous studies have shown that SOD has been elevated in chronic schizophrenic patients. However, decreased SOD activity was found in neuroleptic naïve, first episode schizophrenic patients, in chronic-medicated patients and in chronic-unmedicated patients. The aim of this study was to examine which of the following factors including age, gender, the onset of the disease, the duration, the number of episodes, heredity, psychopathologic symptoms and drug treatment could affect erythrocyte SOD activity in patients with schizophrenia. Methods: This study included 68 consecutive patients with schizophrenia (29 males and 39 females) ranging in age from 18 to 61 years, divided into two age groups (<34 years and >34 years). SOD activity was measured in erythrocyte hemolyzates by Ransod commercially available test. Results: In the group of patients younger than 34 years SOD levels were significantly higher (1381±273 U/gHb, p=0.038) compared to the levels of the older group (1231±206 U/gHb). Gender and heredity did not induce any significant difference in SOD activity between younger and older subgroups. A significant difference in enzyme activity was found between the younger and older subgroups having the onset of the disease after 24 years of age (1408±217 U/gHb vs. 1252±213 U/gHb, p=0.031). The patients of the younger group who had more than one psychotic episode had significantly higher SOD activity (1492±298 U/gHb; p=0.009) than those who had only one episode (1256±177 U/gHb), as well as than the older subgroup with more than one episode (1253±231 U/gHb; p=0.014). Although the duration of the disease did not induce any significant difference in enzyme activity between younger and older subgroups, a significant negative correlation was obtained between SOD activity and the duration of the disease (r=-0.511, p<0.01). No significant differences were found in SOD activity between the subgroups with different PANSS scores. First generation antipsychotics were associated with elevated enzyme activity in both groups. Simultaneous treatment of patients with first generation antipsychotics and second generation antipsychotics induced a significant decrease in SOD activity in the younger group. Conclusion: Our results show that erythrocyte SOD activity is increased in the early phase of schizophrenia and that depends on age of onset of the disease, the number of psychotic episodes, the duration of the disease and medical treatment.

Diagnostic Accuracy of Brain-derived Neurotrophic Factor and Nitric Oxide in Patients with Schizophrenia: A pilot study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) play multiple roles in the developing and adult CNS. Since BDNF and NO metabolisms are dysregulated in schizophrenia, we measured these markers simultaneously in the blood of schizophrenics and assessed their diagnostic accuracy. METHODS: Thirty-eight patients with schizophrenia classified according to demographic characteristics, symptomatologyand therapy and 39 age- and gender-matched healthy controls were enrolled. BDNF was determined by the ELISA technique while the concentration of nitrite/nitrate ([Formula: see text]) was measured by the colorimetric method. RESULTS: Serum BDNF levels were significantly lower (20.38±3.73 ng/mL, P = 1.339E-05), whilst plasma [Formula: see text] concentrations were significantly higher (84.3 (72-121) µmol/L, P=4.357E-08) in patients with schizophrenia than in healthy controls (25.65±4.32 ng/mL; 60.9 (50-76) µmol/L, respectively). The lowest value of BDNF (18.14±3.26 ng/mL) and the highest [Formula: see text] concentration (115.3 (80-138) µmol/L) were found in patients treated with second-generation antipsychotics (SGA). The patients diseased before the age of 24 and the patients suffering for up to one year had significantly lower serum BDNF levels than those diseased after the age of 24 and the patients who were ill longer than one year. Both BDNF and [Formula: see text] showed good diagnostic accuracy, but BDNF had better ROC curve characteristics, especially in patients with negative symptomatology. CONCLUSIONS: BDNF and nitrite/nitrate showed inverse changes in schizophrenic patients. The most pronounced changes were found in patients treated with second-generation antipsychotics. Although BDNF is not specific of schizophrenia, it may be a clinically useful biomarker for the diagnosis of patients expressing predominantly negative symptoms.

Schizophrenia is associated with increased levels of serum Fas and FasL.

BACKGROUND: A growing body of evidence suggests that the apoptotic process is dysregulated in schizophrenia. However, only a few studies have evaluated apoptotic markers in vivo in patients or their cell cultures. METHODS: Serum concentrations of Fas receptor (Fas/APO-1) and Fas ligand (FasL) were measured by ELISA techniques. The differences were tested according to the patients' demographic, clinical and drug treatment characteristics. The clinical accuracy of the examined markers was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: In this case-controlled study both sFas/APO-1 and FasL were significantly higher in the patients with schizophrenia than in the controls. An increase in apoptotic markers was independent of the symptomatology, drug treatment, heredity, the first onset of the disease, the duration of the psychotic disease as well as the tobacco abuse. A significant negative correlation between the duration of the disease and sFasL concentration was found. At the same time, a significant positive correlation was found between sFasL and lymphocyte caspase-3 activity. ROC curve analysis showed that sFasL was the most strongly associated with the presence of schizophrenia. CONCLUSIONS: We can conclude that the extrinsic apoptotic pathway is dysregulated in schizophrenia and sFasL may be a clinically useful disease predictor.

[Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification].

BACKGROUND/AIM: Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. METHODS: The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M) and the patients treated with opiate blocker naltrexone (B). In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD) and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version). Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. RESULTS: Both groups of patients (M and B) had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers. CONCLUSION: The opioid relapse behavior is associated with a marked depression in post-detoxification period. The tested group M had a more expressed depression which is consistent with the literature data. In both tested groups the frequency of relapses was positively correlated with individual addiction variables associated with latent suicidal behavior. Diagnosing and monitoring depression of opiate addicts as well as timely remediation of post-detoxification depression symtoms, could help in prevention of opiate relapse.

Irritable bowel syndrome, anxiety, depression and personality characteristics.

BACKGROUND: Numerous studies have suggested that 54%-100% of patients with IBS may have associated psychiatric illness and personality pathology. This transversal controlled study was realized in order to evaluate anxiety and depression levels, as well as the personality characteristics of patients with IBS and to compare the results obtained with patients with episodes of depression and healthy individuals. SUBJECTS AND METHODS: The experimental group consisted of 30 IBS patients, while two control groups consisted of the same number of inpatients with episodes of depression and healthy individuals from the general population. There were equal number of men and women in the study sample and all subjects were aged between 25 to 65 years. Standard psychometric instruments employed included Hamilton anxiety scale, Zung depression scale, Hamilton depression scale, Minnesota Multiphasic Personality Inventory (MMPI), Eysenck Perosonality Inventory (EPI). RESULTS: The average Hamilton and Zung depression scores were significantly higher in patients with depressive episodes compared with the IBS patients, while the mentioned scores among them were also significantly higher compared with the healthy controls. There were no significant differences between IBS and the group with depressive episodes in the average Hamilton anxiety levels, EPI neuroticism and extraversion levels and MMPI neurotic scales levels (Hs, D, and Hy). The significant differences were observed comparing the IBS patients to healthy individuals. CONCLUSION: The patients suffering from irritable bowel syndrome who asked for medical help (consulters) because of their intestinal symptoms, presented emotional problems such as depression and anxiety and expressed neurotic personality characteristics.

Plasma nitrite/nitrate concentrations in patients with schizophrenia.

BACKGROUND: Nitric oxide (NO) is known to be a signaling molecule with many physiogical functions including apoptotic process regulation. Since apoptosis may contribute to the pathophysiology of schizophrenia, this study was undertaken to determine the plasma concentrations of NO in schizophrenics. METHODS: Nitrite/nitrate (NO(2)(-)/NO(3)(-)) concentrations were measured in plasma from 40 patients with schizophrenia, and 36 age- and gender-matched healthy persons using a colorimetric test. RESULTS: Plasma NO(2)(-)/NO(3)(-) concentrations were significantly higher in patients with schizophrenia (102.8+/-34.7 micromol/L, p<0.0001) than in controls (69.2+/-13.2 micromol/L). Also, mean NO(2)(-)/NO(3)(-) values in female patients and controls were significantly higher (118.2+/-44.7 micromol/L, p<0.001; 74.8+/-16.1 micromol/L, p<0.05, respectively) compared to males (94.7+/-25.3 micromol/L, 67.6+/-10.8 micromol/L). Significant correlation was seen between plasma NO(2)(-)/NO(3)(-) concentrations and heredity, number of episodes and peripheral blood mononuclear cell (PBMC) caspase-3 activity, which was significantly higher in patients than in controls (p<0.05). There was no significant difference in NO(2)(-)/NO(3)(-) concentrations between patients with different Positive and Negative Syndrome Scale (PANSS) scores or between patients treated with haloperidol (97.2+/-31.2 micromol/L) and those treated with other atypical antipsychotic drugs (109.8+/-33.7 micromol/L). Both parameters showed no significant differences between smokers and non-smokers. CONCLUSIONS: This study showed that plasma NO(2)(-)/NO(3)(-) concentrations were significantly increased in patients with schizophrenia, being significantly higher in female than male patients, and showing a significant correlation with heredity, number of episodes and PBMC caspase-3 activity. These results suggest that NO could be considered an inducer or regulator of apoptosis in patients with schizophrenia.