Bjanka Vuksan Ćusa

The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia

Objectives Treatment-resistant schizophrenia (TRS) continues to be a challenge in modern psychiatry. Most of these patients have severe neurocognitive deficits. Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of TRS, but because of potential neurocognitive adverse effects, it is associated with many controversies. The aim of this prospective, open study was to evaluate the effects of ECT augmentation of antipsychotics on cognitive functions in patients with TRS. Methods Overall, 31 inpatients with TRS were included, 16 men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical symptoms and global impression, as well as verbal memory, visual memory, working memory, psychomotor speed, verbal fluency, and executive functioning, was conducted before and after the completion of ECT treatment. Results We ran a series of paired-samples t tests, and the Bonferroni adjustment for multiple comparisons reduced the significance level to P = 0.004. The neurocognitive domains that demonstrated statistically significant improvement were immediate and delayed verbal memory, and executive functioning, whereas statistical trend was observed for visual memory and psychomotor speed. None of the neurocognitive functions exhibited significant deterioration after the ECT treatment. Electroconvulsive therapy was effective in reducing general symptoms of schizophrenia, resulting in more than 30% decrease in the overall symptom severity measured by the Positive and Negative Syndrome Scale. Conclusions Notwithstanding some limitations of this study, the combination of ECT and antipsychotics has improved several neurocognitive domains, without evidence of worsening of any cognitive functions.

The lack of effect of ziprasidone on platelet serotonin concentration in schizophrenic patients

Rationale Ziprasidone is an atypical antipsychotic, with the unique multireceptor-binding profile. If affects multiple serotonergic (5-HT) receptors, inhibits 5-HT transporter (5-HTT) and inhibits synaptic 5-HT reuptake. These effects might be responsible for the antidepressant effect of ziprasidone. Objectives Since there is a lack of in vivo data on the effects of ziprasidone on 5-HT concentration in humans, the aim of the study was to investigate the effect of ziprasidone treatment on platelet 5-HT concentration in patients with schizophrenia or schizoaffective disorders. Methods In and open-label study, the effect of ziprasidone (average dose of 109 mg/day) on platelet 5-HT concentration (determined fluorimetrically) was evaluated at baseline and after 7 and 28 days of treatment in 21 male and female patients with schizophrenia or schizoaffective disorders. Results Ziprasidone treatment for 7 or 28 days did not significantly change baseline platelet 5-HT concentration in male and female schizophrenic patients. Platelet 5-HT concentration was not correlated with gender, age and smoking status of patients. Conclusions There was a lack of effect of ziprasidone treatment on platelet 5-HT concentration in male and female schizophrenic patients. Although the clinical effects of ziprasidone were evident after 28 days of treatment, and ziprasidone has the highest potency among atypical antipsychotics to block 5-HTT, our data did not confirm the hypothesis that ziprasidone treatment decreases platelet 5-HT concentration, at least not in the doses used in our study.

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia

Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. The aim of the present study was to determine the haplotypic and genotypic association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS. Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545 males) were included, while 270 participants met the criteria for TRS. In males, no significant haplotypic and genotypic associations between COMT rs4680 and rs4818 polymorphisms and TRS were detected. However, genotypic analyses demonstrated higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers (p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the presence of the G allele in females was associated with lower risk of TRS. In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.

Antipsychotics do not affect platelet serotonin in schizophrenic patients

RationaleAlthough antipsychotic drugs are prescribed for the treatment of schizophrenia and psychotic disorders, some of these drugs are also reported to possess antidepressant properties. Therefore, they are more frequently used either as a monotherapy or as an addition to antidepressant medication treatment in depression.ObjectivesThe data on the effects of antipsychotic drugs on serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) in vivo when given to patients in therapeutic doses are still scarce.MethodsPatients with schizophrenia or schizoaffective disorders in both male and female patients, were treated with antipsychotic drugs: 25 patients received olanzapine (12.8 ± 2.8 mg/day), 14 patients were treated with typical antipsychotic, fluphenazine N=14 (10.5 ± 2.5 mg/day) and for comparison, 21 patients were treated with ziprasidone (109.0 ± 27.1 mg/day). Platelet 5-HT concentration was determined fluorimetrically and evaluated at baseline and after 28 days in 65 healthy control subjects and in 60 patients.ResultsPlatelet 5-HT concentration did not differ significantly [F(3, 246)=0.597; p=0.677] between medicationfree healthy control subjects sampled at baseline and after 28 days compared to schizophrenic patients sampled before and 28 days after antipsychotics. Tukey’s multiple comparison test revealed that treatment with fluphenazine (p=0.853), olanzapine (p=0.117), or ziprasidone (p=1.000) did not significantly alter platelet 5-HT concentration after 28 days of treatment compared to their baseline values, i.e. values before treatment.ConclusionsAlthough all antipsychotics used in the study possess some antidepressant effects that are assumed to be related to their serotonergic properties, and have been reported to have in vitro binding affinity for human 5-HTT, the present study failed to detect significant in vivo effects of typical (fluphenazine) or atypical (olanzapine, ziprasidone) antipsychotics on platelet 5-HT concentration in schizophrenic patients.