Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms.

Functional polymorphism of matrix metalloproteinase-9 (MMP9) gene is not associated with schizophrenia and with its deficit subtype.

BACKGROUND: The deficit subtype of schizophrenia is hypothesized to constitute a pathophysiologically distinct subgroup of schizophrenia patients suffering from enduring, idiopathic negative symptoms and various neuropsychological deficits. Matrix metalloproteinases (MMPs) are extracellularly acting endopeptidases the substrates of which are matrix and adhesion molecules. Recently, MMP9 has been shown to be involved in various forms of synaptic plasticity, learning and memory consolidation. The primary aim of the present study was to evaluate associations between the functional MMP-9 -1562C/T gene polymorphism and the deficit and non-deficit subtypes of schizophrenia. METHODS: The study was conducted between 2009 and 2012. Deficit schizophrenia was diagnosed using the SDS. The sample consisted of 468 patients, Caucasians, of Polish descent with ICD 10 diagnosis of schizophrenia: 189 [51% males] were included in a non-deficit subgroup, 279 patients [53% males] were included in a deficit subgroup. The control group consisted of 532 subjects, Caucasians, of Polish descent [51% males]. MMP-9 -1562C/T gene polymorphism was genotyped using the fluorescence resonance energy transfer (FRET) method and the Light Cycler System 2.0. RESULTS: The frequencies of genotypes and alleles did not differ between the schizophrenia patients and control group. The deficit and non-deficit patients did not differ in terms of the genotype and allele frequencies. No differences were found in genotype and allele frequencies between the deficit patients and the controls and between the non-deficit patients and the controls. CONCLUSION: We found no evidence for the association between the functional MMP-9 -1562C/T gene polymorphism and deficit/non-deficit subtypes of schizophrenia.

Pharmacogenetics of adverse events in schizophrenia treatment: comparison study of ziprasidone, olanzapine and perazine.

The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.

[The efficacy of cognitive neurorehabilitation with RehaCom program in schizophrenia patients]. / Skutecznosc rehabilitacji neuropsychologicznej z wykorzystaniem programów rehacom u pacjentów z rozpoznana schizofrenia.

UNLABELLED: Schizophrenic patients present cognitive dysfunctions which are currently regarded to be one of endophenotypical markers predisposing to schizophrenia. This indicates neurostructural changes underlying schizophrenia, which can be treated as a neurodegenerative and neurodeveloping disease. AIM: The purpose of this study was to assess the possibility of neuropsychological rehabilitation in schizophrenia. METHODS: 41 participants and 40 control subjects were randomly selected and did not show differences in gender, age and illness duration. Both groups had the diagnosis of paranoid schizophrenia according to ICD-10 criteria and were treated with antipsychotic drugs. Cognitive functions were checked with Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Color -Word Interference Test (SCWT) in the beginning and in the end of the experiment. In the research group each patient was trained with the rehabilitation programs that focused on attention and concentration and topological memory. This group was compared with the control group that was not trained with RehaCom. RESULTS: RehaCom procedures apparently can be useful in neuropsychological rehabilitation of cognitive dysfunctions in patients with diagnosed schizophrenia. Every participant from the research group showed a significant improvement in the training programs, especially in attention/concentration procedure. The analysis of parameters obtained in the neuropsychological tests showed some improvement in neuropsychological assessment in both groups. CONCLUSIONS: Cognitive rehabilitation produces moderate improvement in cognitive functioning. A comprehensive treatment using also new technologies supporting pharmacological treatments and other therapies should result in increased cognitive functioning and as a consequence improvement of quality of patient's life.

The efficacy of cognitive rehabilitation with RehaCom programme in schizophrenia patients. The role of selected genetic polymorphisms in successful cognitive rehabilitation.

INTRODUCTION: Schizophrenic patients present cognitive dysfunctions which are regarded to be one of endophenotypical markers predisposing to schizophrenia. Currently, schizophrenia can be treated as a neurodegenerative and neurodeveloping disease with genetic background. OBJECTIVE: Assessment of the possible positive effect of neuropsychological rehabilitation in schizophrenia, in patients presenting cognitive dysfunctions. An additional aim was to verify the hypothesis that some genetic polymorphisms can be a prognostic factor for success in neuropsychological rehabilitation. MATERIAL AND METHODS: 41 participants and 40 control subjects were randomly selected. Both groups had the diagnosis of paranoid schizophrenia. Cognitive functions were checked with the Wisconsin Card Sorting Test, Trail Making Test, and Stroop Test at the beginning and end of the experiment. In the research group, each patient trained with the rehabilitation programme RehaCom, whereas the control group did not receive such training. Genes COMT rs4680 and BDNF rs6265 were analysed in the genetic part of study. RESULTS: RehaCom procedures appear to be useful in the neuropsychological rehabilitation of cognitive dysfunctions in patients diagnosed with schizophrenia. The research group showed a moderate improvement in the training programmes. Analysis of parameters obtained in the neuropsychological tests showed a slight improvement in both groups. At the present time, analysis of the polymorphisms of genes cannot be treated as a prognostic factor for the success of neuropsychological rehabilitation because statistical analyses showed few dependences with little statistical significance. CONCLUSIONS: Cognitive rehabilitation produces moderate improvement in cognitive functioning.

[The influence of antipsychotic therapy on the cognitive functions of schizophrenic patients]. / Wplyw leków przeciwpsychotycznych na funkcje poznawcze u pacjentów ze schizofrenia.

AIM: The aim of the present study was twofold: 1. to compare the efficacy of three antipsychotics (ziprasidone, olanzapine and perazine) in schizophrenia 2. to compare the improvement in cognitive functioning between groups treated with the three different neuroleptics. METHOD: A total of 58 Caucasian patients diagnosed with paranoid schizophrenia were recruited into the study group. We used the Polish version of the CIDI (Composite International Diagnostic Interview) to obtain ICD-10 diagnoses. The intensity of psychopathological symptoms was examined using the PANSS. The patients were randomly assigned to treatment with perazine, olanzapine or ziprasidone administered as monotherapy for 3 months. The treatment efficacy was measured as a change in the PANSS (Positive and Negative Syndrome Scale) total score from baseline (T0) to 3 months (T1). The WCST (The Wisconsin Card Sorting Test) was used to measure working memory and executive functions in the evaluated patients. Wilcoxon's and Kruskal-Wallis tests were applied to compare changes in the PANSS scores between the treatment groups. To analyze the cognitive functions, Kruskal-Wallis test for the WCST parameters was used. RESULTS: The three antipsychotics similarly reduced the total PANSS score. The WCST parameters in the 3 groups of examined patients using the Kruskal-Wallis test revealed some differences between the three administered antipsychotics. CONCLUSIONS: Results suggest that the short-term efficacy of the atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs did not differ. Based on the analysis, a conclusion can be drawn that the three neuroleptics provided similar improvements in cognitive functioning.

BDNF rs 6265 polymorphism and COMT rs 4680 polymorphism in deficit schizophrenia in Polish sample.

BACKGROUND: Deficit schizophrenia (DS) is distinguished from the group of schizophrenic psychoses based on the presence of primary negative symptoms. It differs from nondeficit (NDS) forms of schizophrenia in dimensions such as risk factors, family history, course of illness and neurobiological differences. The aim of the study was assessment of a potential association of the investigated polymorphisms of the brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes with the deficit syndrome in schizophrenia. METHODS: A cohort of 200 patients with schizophrenia (81 DS and 119 NDS subjects) and a group of 100 control subjects matched for ethnicity, sex and age were recruited. Somatic and psychometric assessment were conducted as well as structured interview about the influence of adverse biological, family and social factors. Genetic analysis of the BDNF (Val66Met) rs6265 and the COMT (Val158Met) rs4680 polymorphisms was performed. RESULTS: We found significant differences between DS and NDS in rs4680 COMT genotype distribution: more homozygous Val/Val were found (31 vs. 17%) in the NDS compared to the DS subgroup. No associations were found between the investigated polymorphisms of the BDNF gene and the presence of schizophrenia either in DS and NDS subgroups. CONCLUSION: The analysis of the COMT rs4680 polymorphism in the present DS and NDS study shows that some genetic factors may be relevant in analyzing the reasons for the differentiation of schizophrenic subtypes.

Some dopaminergic genes polymorphisms are not associated with response to antipsychotic drugs in schizophrenic patients.

BACKGROUND: Therapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients. METHODS: One hundred ninety one Caucasian patients admitted with exacerbation of paranoid schizophrenia were genotyped for polymorphisms of the DRD2 [the ins/del -141C (rs1799732) and exon 8 (rs 71653615)], DRD2/ANKK1 Taq IA(rs 1800497), DAT1 (the 40 bp VNTR), COMT (rs 4680), and MAOA gene (the 30 bp VNTR in promoter). The patients were randomly assigned to the treatment with perazine, olanzapine or ziprasidone given as monotherapy for 3 months. Treatment efficacy was measured from baseline (T0) to T1 (14 days) and T2 (3 months). A retention rate was also assessed at T1 and T2. RESULTS: The three antipsychotics did not differ in terms of reduction of the PANSS score or retention rate at the follow-up. There was no interaction between the investigated polymorphisms and response to the antipsychotic treatment. CONCLUSIONS: The present results suggest that: i) there are no major differences in short-term efficacy or effectiveness of atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs; ii) the studied polymorphisms are not primarily involved in treatment response to antipsychotics in schizophrenia patients.

[Associations between candidate genes with schizophrenia susceptibility and the treatment efficiency]. / Analiza genów kandydujacych zwiazanych z predyspozycja do schizofrenii i z efektem leczenia przeciwpsychotycznego.

AIM: The aim of the study was to find genetic markers which can have influence on susceptibility of paranoid schizophrenia and the treatment efficiency measured by the PANSS (Positive and Negative Syndrome Scale). We analysed the gene polymorphisms: dopamine receptor--DRD2 (Taq 1A, in egzon 8,- 141 C ins/del), dopamine transporter--DAT, kainate receptor--GRIK3, serotonine transporter--SERT, serotonine receptor--5HT2A, mono amine oxidase A--MAO-A, catechol O-methyl transferase--COMT. METHOD: One hundred four Polish patients with the diagnosis of paranoid schizophrenia were recruited as the study group. To obtain the diagnosis meeting the ICD-10 criteria, we used the Polish version of CIDI--Composite International Diagnostic Interview. Exclusion criteria included serious neurological disorders, major somatic disorders impairing cognitive functions and diagnosed mental impairment. The intensity of psychopathological symptoms was examined using the PANSS. Genomic DNA was extracted from leucocytes using the Miller's salting method. Polymorphisms were studied by the PCR (Polymerase Chain Reaction) method using RFLP (Restriction Fragments Length Polymorphism) and VNTR (Variable Number Tandem Repeat) technique. Statistical analyses were performed by the Statistica computer program, specifically Pearson's chi-square test. Associations between the treatment progress and the genotype were studied by analysis of variance (ANOVA). RESULTS: We did not find associations between investigated gene polymorphisms and susceptibility of paranoid schizophrenia. Probably, there is no influence of studied polymorphisms on the treatment efficiency. CONCLUSIONS: No differences were found in the genotypes distribution in the studied gene polymorphisms between the whole schizophrenics and the control group. No association was found between any particular genotype and the effect of antipsychotic treatment.

Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients.

BACKGROUND: D(2) receptor function can be assessed by growth hormone (GH) response to apomorphine. Several association studies between dopamine receptor polymorphisms and results of the apomorphine challenge test with normal and alcohol-dependent subjects yielded inconsistent results. In this pilot study, we tested polymorphisms from the DRD2 region for GH response to apomorphine challenge in more detail. METHODS: Apomorphine challenge tests measuring GH responses on 5 time points were performed on day 1 of alcohol detoxification in 43 patients with alcohol dependence; patients were genotyped for 11 polymorphisms including DRD2, ANKK1, NCAM1 and TTC12. RESULTS: Associations (p<0.05) were found for ANKK1 (rs11604671, rs1800497) and DRD2 (rs6276, rs1076560), which are located on adjacent chromosomal positions. Consistent with PET studies suggesting a reduced D(2) receptor availability in patients carrying the ANKK1 rs1800497 T polymorphism (formerly known as DRD2 TaqI A1) we found a reduced GH response to apomorphine in those subjects. CONCLUSION: This has been the first study showing significant associations between apomorphine-induced GH response and SNPs in DRD2 and ANKK1 in alcohol-dependent patients. In this respect, our preliminary results are in line with other reports which suggested that DRD2 and ANKK1 polymorphisms influence D(2) receptor availability and signal transduction in the dopaminergic pathways. Small sample size in our study limits the generalizability of our results.

[Association of functional genes polymorphisms of key enzymes in the metabolism of biogenic amines with paranoid schizophrenia susceptibility and the influence of these polymorphisms on PANSS results in antipsychotic treatment]. / Zwiazki funkcjonalnych polimorfizmów genów kluczowych enzymów w metabolizmie amin biogennych z wystepowaniem schizofrenii paranoidalnej oraz ich wplyw na wyniki w PANSS pod wplywem leczenia przeciwpsychotycznego.

AIM: The genetic components of the schizophrenia susceptibility are calculated as being 50%. We evaluated the frequency of alleles and genotypes of COMT and MAO-A genes polymorphisms in patients with schizophrenia and in the healthy population. We searched for the associations between genotypes and PANSS results among patients in a three month antipsychotic therapy. METHOD: The study comprised 72 unrelated patients who met ICD-10 criteria for schizophrenia, and 187 unrelated healthy controls. The analysis of COMT and MAO-A genes polymorphisms were performed using the polymerase chain reaction technique (RFLP-restriction fragments length polymorphism and VNTR-variable number tandem repeats). The severity of psychopathological symptoms was measured by the PANSS (Positive and Negative Schizophrenia Scale). RESULTS: We did not find an association between the genotype of COMT and MAO-A genes polymorphisms and schizophrenia. We found statistically significant different allele distribution in MAO gene polymorphism: alleles with three tandem repeats in the promoter region were more frequent among females with schizophrenia. We did not find any association between the genotype of COMT and MAO-A genes polymorphisms and PANSS results in any time periods. Due to a small number of patients in this study the obtained results should be regarded as preliminary.