Jolanta Rabe-Jabłońska

Oxidative stress in blood platelets from schizophrenic patients

Oxidative stress in blood platelets is observed in various diseases, including neuropsychiatric disorders. The aim of our study was to evaluate oxidative stress in blood platelets from patients with schizophrenic disorders by measuring the activity of the platelet antioxidative enzyme, superoxide dismutase (SOD), concomitant with the level of thiobarbituric acid reactive species (TBARS). In blood platelets obtained from schizophrenic patients (with paranoid schizophrenia according to DSM-IV criteria) and from healthy volunteers the level of reactive oxygen species was also measured via chemiluminescence. In resting blood platelets from schizophrenic patients the chemiluminescence was higher than in platelets from control subjects (P < 0.05), but in thrombin-activated platelets an increase (about 53%) of chemiluminescence was observed, however this increase was lower than in thrombin-stimulated platelets from healthy subjects (101.5%). The results indicate that in platelets from schizophrenic patients generation of reactive oxygen species is enhanced. Moreover, we observed that SOD activity in blood platelets from schizophrenic patients was significantly lower than in control platelets and that a correlation exists between increased lipid peroxidation and inhibition of the activity of this antioxidative enzyme in schizophrenic platelets.

Quetiapine, olanzapine and haloperidol affect human plasma lipid peroxidation in vitro.

Objective: Oxidative injury in schizophrenia may be caused not only by pathophysiological processes but partly also by treatment with antipsychotics. The purpose of the present study was to examine and to compare the effects of quetiapine (QUE), olanzapine (OLA) and haloperidol (HAL), at final concentrations corresponding to doses used for treatment of acute episodes of schizophrenia, on plasma lipid peroxidation in vitro, measured by the level of thiobarbituric acid-reactive substances (TBARS). Methods: Blood from 30 healthy volunteers was collected into ACD (citric acid/citrate/dextrose) solution. The drugs in form of active substances were dissolved in 0.01% dimethyl sulfoxide, added to plasma at the final concentrations [QUE (175 and 275 ng/ml), OLA (20 and 40 ng/ml), HAL (4 and 20 ng/ml)] and incubated for 1 and 24 h at 37°C. The level of TBARS was measured spectrophotometrically (according to the Rice-Evans method, 1991). Results: The comparative study in vitro showed that QUE causes a decrease in the TBARS level in plasma, whereas HAL increases the plasma TBARS level. After 24 h of incubation of plasma with QUE or HAL (at lower and higher concentrations),thedifferences in TBARS levels between the drugs were significant (p = 5.9 × 10–4, p = 2.2 × 10–5, respectively). Conclusion: QUE and OLA, contrary to the prooxidative action of HAL, did not induce oxidative stress; moreover, QUE has antioxidant properties.

The first- and second-generation antipsychotic drugs affect ADP-induced platelet aggregation

Objective. Blood platelets play an important role in haemostasis and their hyperaggregability may lead to thrombosis and cardiovascular diseases. Increased incidence of mortality, caused by cardiovascular disease, and the increased risk of thrombotic complication in schizophrenic patients treated with antipsychotics have been reported. The effects of antipsychotic drugs on blood platelet function are not fully explained, therefore the purpose of the present study was to examine and compare the effects of the second-generation antipsychotic drugs used in schizophrenia (clozapine, risperidone and olanzapine), with the effects of the first generation antipsychotic, haloperidol, on the platelet aggregation induced by ADP in vitro. Methods. Blood obtained from healthy volunteers (n=25) collected into sodium citrate was centrifuged (250×g, 10 min) at room temperature to obtain platelet-rich plasma. Aggregation of blood platelets (10 µM ADP) was recorded (Chrono-log aggregometer) in platelet-rich plasma preincubated with antipsychotic drugs (final concentration: clozapine 420 ng/ml, risperidone 65 ng/ml, olanzapine 40 ng/ml, haloperidol 20 ng/ml) for 30 min. Results. Our results showed that all tested drugs inhibit platelet aggregation induced by ADP in vitro. Among studied antipsychotic drugs clozapine and olanzapine significantly reduced platelet aggregability in vitro. In comparison with control platelets (without the drug), clozapine inhibited ADP-induced platelet aggregation by 21% (P=3.7×10−6) and olanzapine by 18% (P=2.8×10−4), respectively. Conclusion. The obtained results indicate that antipsychotic drugs, especially clozapine and olanzapine, contrary to haloperidol, reduced response of blood platelets to ADP measured as platelet aggregation. This suggests that therapy with such antipsychotics, particularly with second-generation antipsychotics, may partly reduce prothrombotic events associated with the increased platelet activation observed in schizophrenic patients. The mechanism of antiaggregatory influence of antipsychotics requires further studies.

PORT (Programme of Recognition and Therapy): the first Polish recognition and treatment programme for patients with an at‐risk mental state

To present the activities of the first early intervention centre in Poland and the Programme of Recognition and Therapy (PORT) run by the centre.

Gender influence in suicidal behaviour of Polish adolescents

Abstract.Objective:The aim of the study was to assess the prevalence and possible suicide attempts and ideation predictors in the school population of girls and boys in the city of Łódź.Method:A selfadministered anonymous questionnaire was distributed to a representative (random) sample of 1663 students, aged 14–21. Boys and girls reporting no suicidal behaviour (NSB) constitute the control groups; the characteristics of these groups were compared to those of the groups with suicidal behaviour (SB), with focus on the associations between different variables and gender, separately for suicidal ideation (SI) and suicide attempts (SA).Results:About 37% of girls and 25% of boys reported suicidal ideation and about 11% and 5%, respectively, suicide attempts. Boys were more likely to make multiple suicide attempts. The relation between SB and the history of psychiatric treatment was the same for both sexes. Boys with SB were significantly more often fascinated with death, and girls were significantly more often exposed to difficult family situations.

Pegylated interferon α and ribavirin therapy may induce working memory disturbances in chronic hepatitis C patients

OBJECTIVE This study was designed to determine the effect of 12-week pegylated IFNalpha plus ribavirin (peg-IFNalpha/RBV) treatment on cognitive performance in chronic hepatitis C (CHC) patients. METHOD Forty-seven CHC patients were consecutively enrolled and divided into two groups: active treatment and control (26 and 21 participants, respectively). Treatment-group patients received peg-IFNalpha/RBV treatment for 48 weeks in standard doses. Control-group patients did not receive the above treatment. Both groups underwent neuropsychological examination at the beginning and after 12 weeks of treatment or observation. Neuropsychological evaluation consisted of Stroop Color-Word Test and Trail Making Test. RESULTS Cognitive performance decreased significantly in the treatment group after 12 weeks of combination therapy, which was not seen in the control group. CONCLUSION The findings suggest that peg-IFNalpha/RBV therapy of CHC patients is related to cognitive performance decline and is a result of IFNalpha-induced neurotransmission abnormalities in the limbic system, dorsolateral prefrontal cortex and anterior cingulate cortex.

Obstetrical complications and Apgar score in subjects at risk of psychosis

The objective of the study was to identify associations between a history of obstetrical complications (OCs) and the future development of symptoms indicating risk of psychosis (At Risk Mental State - ARMS). The frequency of OCs was assessed in 66 ARMS subjects, 50 subjects with the first episode of schizophrenia (FES) and 50 healthy controls. Obstetrical data was obtained from medical documentation and evaluated with the Lewis and Murray Scale. Definite OCs, according to the Lewis and Murray Scale, occurred significantly more frequently in the ARMS group compared to the controls (χ(2) = 7.79, p = 0.005; OR = 4.20, 95% CI = 1.46-12.11), as well as in the FES subjects compared to the controls (χ(2) = 8.39, p = 0.004; OR = 4.64, 95% CI = 1.56-13.20). Apgar scores in the first (Apgar 1) and the fifth minute after birth (Apgar 5) were significantly lower in the FES subjects compared to the controls (for Apgar 1 score Z = 4.439, p < 0.0001; for Apgar 5 score Z = 5.250, p < 0.0001). The ARMS subjects demonstrated significantly lower Apgar 5 scores compared to the healthy controls (Z = 3.458, p = 0.0016). The results indicate that OCs and low Apgar 5 score should be considered important factors in identifying subjects at risk of developing psychosis.

Analysis of vitamin D status in major depression.

Objective. The goals of this study were to determine the serum level of 25 hydroxyvitamin D (25[OH]D), a vitamin D metabolite, in patients with recurrent depression, to assess risk factors for vitamin D deficiency, and to evaluate whether the severity of symptoms of depression and response to treatment were associated with serum vitamin 25(OH)D level. Method. Ninety-one patients 18 to 65 years of age meeting the ICD-10 criteria for recurrent depression were evaluated for depressive symptoms using the Hamilton Depression Rating Scale. The control group consisted of 89 healthy subjects matched according to sex and age. Serum levels of 25(OH)D, parathyroid hormone (PTH), and calmodulin-dependent protein kinase II (Ca2+) were determined in all group members. Results. A significantly decreased serum level of 25(OH)D was observed in the group of patients with recurrent depression compared with healthy subjects. PTH and Ca2+ levels were within the reference values in a substantial majority of patients. No correlation was found between 25(OH)D serum level and age, sex, height, body mass index, disease duration, number of depressive episodes, type of pharmacotherapy, or effectiveness of treatment. Conclusions. Low serum levels of 25(OH)D in patients with recurrent depression suggest that these patients are an important risk group for vitamin D deficiency. However, no relationship was found between these low levels of 25(OH)D and response to treatment for depression. Nevertheless, the results indicate the need to monitor the concentration and supplementation of products containing calciferol in such patients. (Journal of Psychiatric Practice2014;20:329–337)

The effects of the second generation antipsychotics and a typical neuroleptic on collagen-induced platelet aggregation in vitro

OBJECTIVE Antipsychotics are widely used in psychiatry, and consequently a lot of their side effects have been reported. One of them is cardiovascular disease leading to increased risk of stroke, thrombosis, pulmonary, embolism, in which hyperactivation of blood platelets is involved. The purpose of the present study was to examine the effects of the second generation antipsychotics (SGAs) such as clozapine, risperidone, and olanzapine, and a typical neuroleptic - haloperidol - on the one step of platelet activation-platelet aggregation induced by collagen in vitro. Blood was collected into buffered sodium citrate (3.8%) and centrifuged to get platelet-rich plasma (PRP). In PRP (2x10(8) platelets/ml) obtained from healthy volunteers that was incubated with antipsychotics (clozapine, risperidone, olanzapine, haloperidol; 30 min) aggregation of blood platelets was measured using a Chrono-Log Lumi-aggregometer. Aggregation of platelets was measured after stimulation of platelets with 1 microl of collagen (2 microg/ml). RESULTS Clozapine, like haloperidol reduced platelet aggregation induced by collagen (inhibition of platelet aggregation reached about 20%) (P=1x10(-5) and P=0.003, respectively). Risperidone had also a weak antiaggregatory effect (P=0.05). Among tested antipsychotics only olanzapine had no effect on collagen-stimulated platelet aggregation (P>0.05). CONCLUSION The obtained results indicate that the difference in action of tested drugs on platelet aggregation may dependent on the various chemical structures of these drugs. Clozapine, risperidone and haloperidol are structurally diverse, and they all significantly reduce platelet aggregability induced by collagen. On the other hand, a close structural analog of clozapine - olanzapine - did not inhibit platelet aggregation. However, mechanism of antipsychotics action on blood platelets is not clear. Moreover, it seems that clozapine, risperidone and haloperidol treatment due to antiaggregatory action may have even some antithrombotic effects.

Effectiveness and clinical predictors of response to combined ECT and antipsychotic therapy in patients with treatment-resistant schizophrenia and dominant negative symptoms.

The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode.