Krzysztof Kucia

Neuroleptics normalize increased release of interleukin-1β and tumor necrosis factor-α from monocytes in schizophrenia

Abstract Some recent reports show that schizophrenia is accompanied by changes in lymphocyte activity. This study investigated the activity of monocytes by determining their release of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Monocytes were immunomagnetically isolated from the peripheral blood of schizophrenic patients before and after neuroleptic medication and stimulated by lipopolisaccharide (LPS) in vitro. The monocytes of schizophrenic patients released significantly higher amounts of IL-1β and TNF-α than those of healthy controls. Treatment with the typical neuroleptics haloperidol and perazine decreased the release of IL-1β and TNF-α to the control levels. The study has shown that the activity of monocytes is increased in schizophrenia and that neuroleptic treatment normalizes this activity.

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset.

Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFα) gene polymorphisms with paranoid schizophrenia in a Polish population.

Numerous reports have brought attention to the potential role of cytokines in schizophrenia. The aim of the study was to determine whether polymorphisms of IL-2, IL-6, and TNFα genes are risk factors for development of paranoid schizophrenia in a Polish population. Promoter polymorphisms of IL-6 (rs1800795), TNFα (rs1800629), and IL-2 (rs2069762) genes in patients (N=115) and controls (N=135) were genotyped by PCR-RFLP and AS-PCR methods, respectively. Genotype TT and allele T for IL-2 polymorphism, and genotype AA and allele A for TNFα polymorphism were found to be significantly associated with paranoid schizophrenia. Similarly, haplotypes CTA and GTA increased the risk (4.4 times and 5.9 times, respectively) of schizophrenia. To reveal associations between Positive and Negative Symptom Scale subscales and age at onset of schizophrenia, the authors used a novel method called Grade Correspondence Analysis. This analysis revealed that patients with early age at onset have higher scores on the Negative and General subscales of PANSS, and, in that group of patients, haplotype CTA was the most represented. As far as is known, this analysis was used for the first time with reference to genetic data.

BDNF val66met Polymorphism Is Associated With Age at Onset and Intensity of Symptoms of Paranoid Schizophrenia in a Polish Population

The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n = 179), as well as healthy individuals (n = 196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

Association Between C-281A and Val66met Functional Polymorphisms of BDNF Gene and Risk of Recurrent Major Depressive Disorder in Polish Population

According to neurotrophic hypothesis, brain-derived neurotrophic factor (BDNF) is the potential candidate involved in the pathogenesis of depression. We examined the influence of C-281A (rs28383487) and val66met (rs6265) functional polymorphisms in BDNF gene on vulnerability to major depressive disorder, recurrent (MDD-R), in a Caucasian population. To our knowledge, this is the first case-control study to examine C-281A polymorphism in MDD-R. Genetic studies assessing the relationship between val66met polymorphism and major depression have yielded ambiguous results. We conducted a comparison of allele and genotype frequencies between 116 in-patients with MDD-R and 218 healthy subjects. Analyses were performed for whole groups as well as according to sex. Haplotype analysis was also performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of single nucleotide polymorphisms (SNPs). C-281A and val66met polymorphisms are in a linkage disequilibrium (LD). This study failed to find an association between C-281A polymorphism with MDD-R, but such an association was found in the case of val66met polymorphism. The val/val genotype was more frequent in depressed individuals compared to the control group, both in total analysis and after stratification by sex. The val allele is connected with a higher risk of MDD-R development in men than in women. Correspondence analysis has shown that the co-presence of genotypes val/val and C/C is connected with a higher risk of MDD-R development (odds ratio [OR] = 2.05, p < 0.01) compared to other genotype combinations in both analysed SNPs. Haplotype analysis has shown a significantly lower frequency of met-C haplotype in depressed individuals compared to the control group.

In-vitro Immunomodulatory Effects of Haloperidol and Perazine in Schizophrenia

Summary: There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.

Interleukin-1B promoter (-31T/C and -511C/T) polymorphisms in paranoid schizophrenia.

Department of Medical Genetics, Medical University of Silesia, Sosnowiec, Department of Psychiatry and Psychotherapy, Medical University of Silesia, Katowice and Department of Instrumental Analysis, Division of Statistics, Medical University of Silesia, Sosnowiec, Poland Correspondence to Paulina Borkowska, PhD, Department of Medical Genetics, Medical University of Silesia, Ostrogorska 30, 41-200 Sosnowiec, Poland Tel/fax: + 48 32 364 14 01; e-mail: paubor85@gmail.com

Heat shock protein 70 gene polymorphisms are associated with paranoid schizophrenia in the Polish population

HSP70 genes have been considered as promising schizophrenia candidate genes based on their protective role in the central nervous system under stress conditions. In this study, we analyzed the potential implication of HSPA1A +190G/C, HSPA1B +1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia in a homogenous Caucasian Polish population. In addition, we investigated the association of the polymorphisms with the clinical variables of the disease. Two hundred and three patients with paranoid schizophrenia and 243 healthy controls were enrolled in the study. Polymorphisms of HSPA1A, -1B, and -1L genes were genotyped using the PCR-RFLP technique. Analyses were conducted in entire groups and in subgroups that were stratified according to gender. There were significant differences in the genotype and allele frequencies of HSPA1A polymorphism between the patients and controls. The +190CC genotype and +190C allele were over-represented in the patients and significantly increased the risk for developing schizophrenia (OR = 3.45 and OR = 1.61, respectively). Interestingly, such a risk was higher for females with the +190CC genotype than for males with the +190CC genotype (OR = 5.78 vs. OR = 2.76). We also identified the CGT haplotype as a risk haplotype for schizophrenia and demonstrated the effects of HSPA1A and HSPA1B genotypes on the psychopathology and age of onset. Our study provided the first evidence that the HSPA1A polymorphism may potentially increase the risk of developing paranoid schizophrenia. Further independent analyses in different populations to evaluate the role of gender are needed to replicate these results.

Electroconvulsive therapy for major depression in an elderly person with epilepsy

The case of a 72-year-old woman with a history of 40 years of epilepsy and medication-refractory severe depression is described. Despite the chronicity of the present depressive episode, mild MRI pathology and somatic complications, especially pneumonia and drug-induced hyponatraemia, we observed rapid and complete remission of depressive symptoms in the course of ECT. Neither cognitive impairment nor a perceptible influence on the neurological illness was seen, and no increase in seizure threshold has been observed during the course of 2 years maintenance ECT treatment. This article is offered in an attempt to enrich the clinical literature in this field and therefore encourage psychiatrists to consider ECT and MECT as a safe and efficacious option in epileptic patients with major depressive disorder.