Safety of the electroconvulsive therapy and amisulpride combination

BACKGROUND: Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. SUBJECTS AND METHODS: Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. RESULTS: Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. All adverse effects resolved within 24 hours. No side effects of any kind were observed in 7 and 8 cases in the study and control groups, respectively. CONCLUSIONS: This was the first study that examined the safety of amisulpride-ECT combination in schizophrenia. Comparing the side-effects between the study and control groups, no significant differences were detected in terms of their types or frequency. The amisulpiride-ECT combination appears to be a safe treatment option

O advento do tratamento psiquiátrico moderno: a terapia convulsiva de László Meduna

Convulsive therapy (COT) is a major European contribution to the psychiatric armamentarium and biological psychiatry. COT was introduced in psychiatry by László Meduna, a Hungarian neuropsychiatrist. All subsequent publications about the first patient treated with COT, Zoltán L (ZL), were based on Meduna's papers and autobiography. After 4 years of catatonic stupor, ZL received camphor-induced COT which resulted in full remission and discharge from the institution. The aim of this paper is to reconstruct ZL's case history from the original case notes-partly written by Meduna himself-which were recovered from the archives of the National Institute of Psychiatry and Neurology. The case notes show that ZL repeatedly received COT between 1934 and 1937, first with camphor and then with cardiazol induction. After the first course of COT the catatonic stupor was resolved and the psychotic symptoms subsided. However, the remission lasted for only a few months and was followed by a relapse. Despite repeated courses of COT, ZL never became symptom free again, was never discharged and died in the Institute in 1945. This historical case is discussed from both the diagnostic and therapeutic points of view, and an attempt is made to explain the possible reasons for the discrepancies found between Meduna's account and ZL's case notes.A terapia convulsiva (TC) constitui uma das principais contribuições européias ao tratamento psiquiátrico moderno e à psiquiatria biológica. A TC foi introduzida na psiquiatria em 1934 por László Meduna, neuropsiquiatra húngaro. As publicações subseqüentes sobre o primeiro paciente tratado com TC, Zoltán L (ZL), baseiam-se nos artigos e na autobiografia de Meduna. De acordo com essas referências, após quatro anos de estupor catatônico, ZL recebeu TC induzida por cânfora que resultou em plena remissão dos sintomas esquizofrênicos, culminando com alta da instituição. Este artigo reconstrói a história do caso de ZL a partir da recente recuperação de anotações - algumas escritas pelo próprio Meduna - dos Arquivos do Instituto Nacional de Psiquiatria e Neurologia (Hungria). Essas anotações mostram que ZL recebeu repetidas sessões de TC entre 1934 e 1937, primeiramente induzidas por cânfora e depois por cardiazol. A primeira série de TC resultou na suspensão do estupor catatônico e na remissão parcial da psicose. Entretanto, a remissão foi breve e, a despeito de repetidas sessões de TC, ZL nunca esteve inteiramente livre de sintomas, nunca teve alta hospitalar e veio a falecer no Instituto em 1945. Na discussão do caso de ZL, tentamos explicar as possíveis razões das discrepâncias entre o relato de Meduna e as notas originais do prontuário médico

Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice

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Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by bayesian relevance and effect size analysis.

In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL) or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52x10(-4); OR = 2.00). The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21x10(-3); OR = 0.55), which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01). The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful supplementary to the traditional frequentist-based statistical method

Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance

Background: We carried out a candidate gene association study in pediatric acute lymphoblastic leukemia (ALL) to identify possible genetic risk factors in a Hungarian population. Methods: The results were evaluated with traditional statistical methods and with our newly developed Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) method. We collected genomic DNA and clinical data from 543 children, who underwent chemotherapy due to ALL, and 529 healthy controls. Altogether 66 single nucleotide polymorphisms (SNPs) in 19 candidate genes were genotyped. Results: With logistic regression, we identified 6 SNPs in the ARID5B and IKZF1 genes associated with increased risk to B-cell ALL, and two SNPs in the STAT3 gene, which decreased the risk to hyperdiploid ALL. Because the associated SNPs were in linkage in each gene, these associations corresponded to one signal per gene. The odds ratio (OR) associated with the tag SNPs were: OR = 1.69, P = 2.22x10-7 for rs4132601 (IKZF1), OR = 1.53, P = 1.95x10-5 for rs10821936 (ARID5B) and OR = 0.64, P = 2.32x10-4 for rs12949918 (STAT3). With the BN-BMLA we confirmed the findings of the frequentist-based method and received additional information about the nature of the relations between the SNPs and the disease. E.g. the rs10821936 in ARID5B and rs17405722 in STAT3 showed a weak interaction, and in case of T-cell lineage sample group, the gender showed a weak interaction with three SNPs in three genes. In the hyperdiploid patient group the BN-BMLA detected a strong interaction among SNPs in the NOTCH1, STAT1, STAT3 and BCL2 genes. Evaluating the survival rate of the patients with ALL, the BN-BMLA showed that besides risk groups and subtypes, genetic variations in the BAX and CEBPA genes might also influence the probability of survival of the patients. Conclusions: In the present study we confirmed the roles of genetic variations in ARID5B and IKZF1 in the susceptibility to B-cell ALL. With the newly developed BN-BMLA method several gene-gene, gene-phenotype and phenotype-phenotype connections were revealed. We showed several advantageous features of the new method, and suggested that in gene association studies the BN-BMLA might be a useful supplementary to the traditional frequentist-based statistical method

Evaluation of a Partial Genome Screening of Two Asthma Susceptibility Regions Using Bayesian Network Based Bayesian Multilevel Analysis of Relevance

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA). This method uses Bayesian network representation to provide detailed characterization of the relevance of factors, such as joint significance, the type of dependency, and multi-target aspects. We estimated posteriors for these relations within the Bayesian statistical framework, in order to estimate the posteriors whether a variable is directly relevant or its association is only mediated. With frequentist methods one SNP (rs3751464 in the FRMD6 gene) provided evidence for an association with asthma (OR = 1.43(1.2–1.8); p = 3×10−4). The possible role of the FRMD6 gene in asthma was also confirmed in an animal model and human asthmatics. In the BN-BMLA analysis altogether 5 SNPs in 4 genes were found relevant in connection with asthma phenotype: PRPF19 on chromosome 11, and FRMD6, PTGER2 and PTGDR on chromosome 14. In a subsequent step a partial dataset containing rhinitis and further clinical parameters was used, which allowed the analysis of relevance of SNPs for asthma and multiple targets. These analyses suggested that SNPs in the AHNAK and MS4A2 genes were indirectly associated with asthma. This paper indicates that BN-BMLA explores the relevant factors more comprehensively than traditional statistical methods and extends the scope of strong relevance based methods to include partial relevance, global characterization of relevance and multi-target relevance

Catatonia in disulfiram intoxication - a case report and a brief overview of the literature

Catatonic syndromes could accompany a variety of psychiatric and medical conditions. The most common conditions underlying catatonia are affective disorders followed by schizophrenia, but several medical conditions including intoxications affecting the central nervous system can also present with catatonic signs and symptoms. Therapeutic doses of disulfiram could induce catatonia with or without accompanying psychosis or mood disorder. A case of disulfiram intoxication manifesting with catatonia is reported here together with a brief overview of the literature. A patient was admitted to the toxicology ward after a suicide attempt with approximately 20 g of disulfiram. On transfer to the psychiatric ward, she was sitting still, in a semi-stuporous state and displayed motiveless resistance to instructions or attempts to move (active negativism). She was unresponsive to most of the questions (mutism), occasionally verbigerated 1-2 words and stared for more than 20 seconds between shifting attention. After developing a comatosus state her treatment continued at the toxicology ward, where a contrast-enhanced computer tomography scan revealed bilateral emollition of 1.5 cm diameter in both nucleus lentiformis at the level of the third ventricle. Following treatment her condition improved and she benefited of rehabilitation facility and a second psychiatric treatment. She was discharged free of neurological and psychiatric symptoms. In conclusion, we underscore the importance of accurate diagnosis of the underlying psychiatric or medical condition when encountering a fast emerging catatonic syndrome and focus first on treating the causative condition while simultaneously attempting symptomatic treatment of catatonia

Weekly Patterns of Suicide and the Influence of Alcohol Consumption in an Urban Sample = Az alkoholfogyasztás hatása az öngyilkossági halálozás megoszlására a hét egyes napjain városi lakosság körében

Background and purpose – The weekly fluctuation in suicide rates is influenced by several factors including sex, psychiatric illness and alcohol dependence. The purpose of this study is to explore the impact of current alcohol use on suicide rates across the days of the week in urban population. Methods – Data on sex, date of death, results of blood and/or urine alcohol tests and history of alcohol dependence in suicide victims over the 1997-2002 period were retrieved from a forensic database in two cities in Chuvash Republic. Results – Over the six-year study period, 1,379 suicides were committed, 59% of them under the influence of alcohol. The peak incidence for men and women regardless of previous alcohol consumption was on Wednesdays and Mondays, respectively. The overall suicide rate was highest on Mondays and lowest on Thursdays. Both sexes were less likely to commit suicide during holidays than on weekends or workdays while intoxicated with alcohol. Conclusion – In this urban sample, the distribution of suicide across weekdays only partly followed the international pattern. The peak incidence of suicide showed sex difference, with the highest incidence for women on Mondays and for men on Wednesdays. The higher suicide rate on workdays might be accounted for by work-related stress, while the lower rate on weekends could be explained that people usually drink alcohol in the comforting company of family or friends, which reduces psychological tension and suicidal ideation. The majority of men consumed alcohol before committing suicide, regardless of the day of the week, while this observation was true for women only on Fridays and Sundays. Alcohol consumption greatly contributes to suicidal behavior in Chuvash Republic. Háttér és cél – A hét egyes napjaira eső öngyilkosságok arányát számos tényező befolyásolja. Ezek közé tartozik a nem, a pszichiátriai betegség és az alkoholfüggőség. Kutatásukban a szerzők az alkoholfogyasztás hatását vizsgálják a hét egyes napjain bekövetkező öngyilkossági halálozásra a Csuvas Köztársaságban. Módszerek – Igazságügyi orvostani adatbázisból, az 1997 és 2002 között öngyilkosság miatt a Csuvas Köztársaság két nagyvárosában elhunytak adataiból a nemre, a halálozás napjára, a vér- és vizeletalkohol-teszt eredményére, valamint az alkoholfüggőségre vonatkozó adatok kerültek feldolgozásra. Eredmények – A vizsgálat 6 éves időszakában 1379 öngyilkosságot követtek el, ennek 59%-át alkohol hatása alatt. A nők leggyakrabban hétfőn, míg a férfiak szerdán követték el az öngyilkosságot. Összességében az öngyilkossági halálozás hétfőn volt a legmagasabb, csütörtökön a legalacsonyabb. Ünnepnapokon mindkét nemben alacsonyabb volt az ittasan elkövetett öngyilkosság kockázata, mint hétköznapokon vagy hétvégén. Következtetések – A vizsgált városi lakosokból álló mintában az öngyilkosságok heti megoszlása csak részben követte az irodalmi adatokat. A hét egyes napjain bekövetkező öngyilkossági halálozás nemi különbséget mutatott; nőknél hétfőn, férfiaknál szerdán volt a legmagasabb. A munkanapokon ittasan elkövetett magasabb számú öngyilkosság a munkával kapcsolatos stresszel hozható összefüggésbe, a hétvégi alacsonyabb arányok pedig azzal, hogy ilyenkor az alkoholfogyasztás általában családtagok vagy barátok kellemes társaságában történik, ami csökkenti a feszültséget és az öngyilkossági gondolatokat. A férfiak többsége alkoholt fogyasztott az öngyilkosság elkövetése előtt, míg nőknél ez csak pénteken és vasárnap volt megfigyelhető. Az alkoholfogyasztás jelentős mértékben hozzájárul az öngyilkossági magatartáshoz a Csuvas Köztársaságban

DO PREVIOUS OFFENCES PREDICT VIOLENT ACTS IN PSYCHIATRIC PATIENTS? A RETROSPECTIVE STUDY IN HUNGARY.

AIM: To investigate the presence of offences in the previous past history of perpetrators of violent acts who have undergone forced medical treatment. METHODS: The documentation of all patients released over a 10-year period from the National Institute of Forensic Psychiatry (IMEI) was reviewed. A comparison was drawn between patients who were convicted of any type of offense before the violent act (patients with previous offences-PPO) and those who were not (patients with no previous offences-PNO). RESULTS: Eighty-six (29%) and 208 (71%) patients formed the PPO and PNO groups, respectively. Prior contact with psychiatric services was significantly higher in the PPO group (p=0.038) and this group was also more likely to offend under the influence of a psychoactive substance (p<0.001). Exceptional brutality and other qualifying factors were more frequent in the PNO group (p=0.019). CONCLUSION: As IMEI is the only forensic institution in Hungary, the picture presented here reflects the situation in the entire country. A recidivism rate of 29% is within the internationally published range