Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder.

Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. METHODS: In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. RESULTS: We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. CONCLUSION: Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

Immunological reactions after measles vaccination.

Evaluation of immunological reactions after vaccination with attenuated measles virus wasbased on determination of the level of hemagglutination-inhibition (HI) and neutralizing (N) antibodies, their location in basic groups of immunoglobulins, and the degree of blastic transformation induced by phaseolin. The picture of lymphocyte chromosomes of the peripheral blood was also investigated. HI and N antibodies were detected not earlier than on the 14th day after vaccination, reaching a peak on the 30th day. Sera were fractioned on Sephadex G-200 gel or centrifuged in sucrose-density gradient. On the 14th day activity of antibodies was located mainly in IgM fractions, and in a later period mainly in IgG and partly in IgA and IgM. Decrease in blastic transformation was found on the 7th day after vaccination, when HI and N antibodies were not detectable. Further decrease in transformation was observed on the 14th day after vaccination. Mitotic indexes increase significantly only on the 30th day after vaccination. For the whole period of observation there were no changes in the number and structure of chromosomes.

An automated dosimetry system for microwave and thermal exposure of biological samples in vitro.

A waveguide exposure system with automated sample temperature measurement is described. This system provides on-line determination of the temperature profile over time of biological samples in vitro. It allows automated computation of the specific absorption rate determined from heating/cooling curves, uses minimally-perturbing thermometry, is biocompatible and can be used for measurements of both microwave and conventional heating.

The development of biomedical approaches and concepts in radiofrequency radiation protection.

The approaches and concepts used in the development of radiofrequency radiation (RFR) protection guidelines evolved over the past quarter of a century. The values of exposure limits (EL) proposed by various groups are converging. Early guides specified ELs in incident power density. Recent ELs are based on considerations of the relationship between bioeffects and the magnitude of the whole body average specific absorption rate (WBA-SAR) and current densities induced in the body. Both these quantities may be considered as dosimetric ones. Thresholds for untoward health effects expressed in terms of these quantities were suggested, and may be considered as basic ELs. It is possible to derive a frequency-dependent relationship between incident RFR fields and WBA-SAR and/or induced current densities in the body. ELs specified for the purpose of determining compliance in terms of electric and magnetic field strengths or equivalent plane-wave power density existing at a point where a person could be present, but measured in the absence of the exposed subject, may be considered as derived working limits. The rationales offered for the recommended ELs indicate that the principal consideration in establishing limits for frequencies of 10 MHz and higher is the prevention of thermal injury, thermal being defined as relatable to heating, i.e. an increase in temperature. At lower frequencies, below 100 kHz or 30 kHz, direct effects on membranes of nerve and muscle cells may be the limiting factor. An additional consideration is the hazard of shock and burns from contact with ungrounded large metal objects that are charged by RFR fields. Recent advances in RFR dosimetry led to concerns that exposure to presently accepted derived ELs may result in large local SARs and induced current densities in certain parts of the body. The present review concludes that further refinements to the basis for RFR should be introduced. Threshold for health hazards should be investigated taking into account both direct and thermal bioeffects of RFR. The dose-thermal effects relationships should be quantified using the concepts of SAR, SA and thermal dosage. Several unresolved questions, such as the biological basis for SAR time-averaging, and the limitation of pulse peak power, are briefly discussed.

Radiofrequency radiation exposure limits in Eastern Europe.

Eastern European standards on radiofrequency radiation (RFR) exposure limits (EL) are reviewed. These standards are mandatory. Additional standards specify requirements for equipment and methods for RFR measurements to determine compliance. The standards are based on USSR ELs with the exception of Poland and Czechoslovakia, where different approaches to exposure limitation were used. According to informal private communications, a new joint recommendation on RFR ELs for all countries belonging to the Council of Mutual Economic Cooperation (COMECON) is being developed. As far as can be judged from recent USSR publications, the new recommendations will establish ELs at levels comparable to those indicated in the international guidelines developed by the International Non-Ionizing Radiation Committee of the International Radiation Protection Association (INIRC/IRPA).

Modulation of mammalian immunity by electromagnetic radiation.

There have been reports that electromagnetic radiation (EMR) alters the function of the immune system; however, these reports are often contradictory. This review reexamines the literature and attempts to evaluate the data on potential mechanisms of interaction of EMR on mammalian immune function. This report concludes that there is no convincing evidence that EMR effects on the human immune system are a health hazard. It was suggested by some authors that long-term EMR exposure may impair immune surveillance, and hypothetically thus facilitate tumor growth. Additional research is needed to prove or disprove this hypothesis. Available data indicate that EMR exposure does not affect the ability of cells of the immune system to respond to a subsequent challenge. However, the time-course and magnitude of the response may be affected by exposure following stimulation. Research to date provided evidence that at least at some frequencies and/or amplitude and pulse modulations, the site of primary interaction of EMR is at the cell membrane. However, it was shown that one specific response, the increase in B complement-receptor positive lymphocytes (Cr+) in the mouse is under genetic control by a single gene localized on chromosome 5. It is suggested that cells of the immune system are a convenient model for further studies on mechanisms of EMR interaction with living systems. Future research should be directed at exploring beneficial medical applications of EMR modulation of immune responses.

[Genetic factors in the etiology of anorexia nervosa]. / Czynniki genetyczne w etiologii jadlowstretu psychicznego.

Anorexia nervosa (AN) is a disease of complex ethiopatogenesis. Population genetics studies suggest a significant role of genetic factors in the morbidity risk. Family and twin studies allow for the estimation of the heritability--the influence of genetic factors on the specific phenotype--of the anorexia nervosa in 50-80%. Due to the low prevalence of the disease, the adoption studies have not been performed. The rapid development of the molecular biology methods gives possibility for the searching of the specific genes increasing the risk of anorexia nervosa. Linkage studies are based on scanning the whole genome for loci associated with susceptibility to a certain disease. In the preliminary studies, no linkage was found between anorexia nervosa and the markers on the chromosomes 1-5, 13 and X. In the association studies, relationship between vulnerability to AN and polymorphism in 5-HT2a receptor and uncoupling proteins gene were reported. These results need further confirmation.

[Detection of anti-Borna disease virus antibodies in patients hospitalized in psychiatric hospitals located in the mid-Western region of Poland]. / Przeciwciala prezeciwko wirusowi choroby Borna u pacjentów hospitalizowanych w szpitalach psychiatrycznych na terenach województw lubuskiego i wielkopolskiego.

Borna Disease Virus (BDV) is single stranded RNA virus, which may infect a wide range of animal species. Manifestations of the experimental BDV infection show some resemblance to psychopathological symptoms of mental disorders in humans. Several reports suggest the higher prevalence of anti-BDV antibodies in psychiatric patients than in healthy controls. However, the seroprevalence of anti-BDV antibodies varied due to the different serological methods used in the previous studies. Electrochemiluminescence Immunoassay (ECLIA) is a recently developed, highly specific method of detecting antibodies directed toward two BDV proteins: p24 and p40. We used the ECLIA method for the assessment of seropositivity in 946 psychiatric patients hospitalized in the psychiatric hospitals in the western part of Poland. All patients were clinically diagnosed with ICD-10 criteria. Anti-p40 antibodies have not been found in the studied sample. We found anti p-24 antibodies in 23 cases, which give the seroprevalence rate of 2.4%. This result is consistent with the outcome of Japanese population assessment, done with the same methodology. The seropositive cases did not show diagnostic specificity. We did not find statistically significant gender differences in rate of seropositivity. The seroprevalence of anti-BDV antibodies was not significantly different in patients of urban and rural residence, and in patients of different age groups. This is the first demonstration of anti-BDV antibodies in the Polish population of patients hospitalized in psychiatric hospitals.