Maintenance electroconvulsive therapy in schizophrenia.

BACKGROUND: The aim of our retrospective naturalistic observational study was to describe the use of maintenance electroconvulsive therapy (M-ECT) in chronic pharmacoresistant schizophrenia. SUBJECTS AND METHODS: We delineated 19 cases of chronic pharmacoresistant schizophrenia (females N=12) recently treated with maintenance electroconvulsive therapy at the Havlickuv Brod Psychiatric Hospital in the Czech Republic. Demographic, clinical and treatment variables were recorded. RESULTS: M-ECT, when applied weekly to monthly mostly over a period of several years, was of no benefit in the treatment of chronic hallucinations and/or delusions. However, it did prove beneficial (p<0.001) in removing chronic serious symptoms like suicidal or violent behavior, automutilation, refusal of food or liquids, stupor or catatonia. Even though almost all of our patients remained hospitalized, we were nonetheless able to transfer them to an unlocked psychiatric ward and let them out for walks or occupational therapy with almost no need for using restraint. No serious adverse side effects of M-ECT were found. CONCLUSIONS: Our study is limited by using only one simple standardized measurement (Clinical Global Impression - Severity) that was retrospective. Another limitation of our retrospective study was that the subjects had not been regularly tested for their cognitive functions. According to our results, M-ECT mitigates the impact of the disease and improves social functioning of the patients. M-ECT does not treat chronic schizophrenia but does make the lives of patients more tolerable. We suggest further research into M-ECT and its clinical application in chronic pharmacoresistant schizophrenia.

Observational cohort study of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS).

Introduction and Aim: Hepatic encephalopathy (HE) is a common complication of transjugular intrahepatic portosystemic shunting (TIPS). It is associated with a reduced quality of life and poor prognosis. The aim of this study was to compare two groups of patients who did and did not develop overt HE after TIPS. We looked for differences between these groups before TIPS. MATERIALS AND METHODS: A study of 895 patients was conducted based on a retrospective analysis of clinical data. Data was analyzed using Fisher's exact test, Chi-square, Mann Whitney test, unpaired t-test and logistic regression. After the initial analyses, we have looked at a regression models for the factors associated with development of HE after TIPS. RESULTS: 257 (37.9%) patients developed HE after TIPS. Patients' age, pre-TIPS portal venous pressure, serum creatinine, aspartate transaminase, albumin, presence of diabetes mellitus and etiology of portal hypertension were statistically significantly associated with the occurrence of HE after TIPS (p < 0.01). However, only the age, pre-TIPS portal venous pressure, serum creatinine, presence of diabetes mellitus and etiology of portal hypertension contributed to the regression model. Patients age, serum creatinine, presence of diabetes mellitus and portal vein pressure formed the model describing development of HE after TIPS for a subgroup of patients with refractory ascites. CONCLUSION: we have identified, using a substantial sample, several factors associated with the development of HE after TIPS. This could be helpful in further research.

Epidemiology and risk factors of schizophrenia.

Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition.

The complex etiology of schizophrenia - general state of the art.

The etiology of schizophrenia is complex. The aim of this article is to present a global view of the causes of schizophrenia and their interconnectivity. Recent genetic research into schizophrenia is based on genome-wide association studies, the assessment of DNA copy number variations, and the concept of endophenotypes. A lot of suspected genes have already been identified, mostly relating to neurodevelopment, neuroplasticity, immunology and neuroendocrinology. Gene-environment interactions (G×E) reflect genetic variation in susceptibility to the environment. Psychosocial stress and cannabis abuse seem to be the most important environmental factors in schizophrenia etiology. Epigenetic mechanisms, particularly DNA methylation, histone modifications, and non-coding RNAs are the most important linking factor among the genetic and prenatal environmental variables in the etiology of schizophrenia. Postnatal risk factors (e.g., stress, urbanicity, cannabis use) may also affect the risk of schizophrenia via the potentiation of vulnerable brain pathways. Many questionable issues pertaining to G×E assessment of schizophrenia still persist and relate to the exact assessment of environmental agents as well as psychopathology. In future research concerning G×E in schizophrenia, the study samples should be adequately large, schizophrenia endophenotypes should be involved, prospective studies should be supported, environmental causative factors as well as psychopathology should be assessed in a quantitative way, the multiple interactions among the variety of environmental and genetic variables should be evaluated, and epigenetic factors should not be neglected. The EU-GEI project of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (2010-2015) may become a milestone in the schizophrenia G×E research.

Is Mild Cognitive Impairment a Precursor of Alzheimer's Disease? Short Review.

Mild Cognitive Impairment (MCI) may be a precursor of Alzheimer's disease (AD). There is a boundary area between normal aging and dementia. In practice, the term "age related cognitive decline" has been used interchangeably with "normal aging". Alternatively, the term "aging associated cognitive decline" was introduced and defined by a performance on a standardized cognitive scale focused on learning and memory, attention and cognitive speed, language, or visuoconstructional abilities. The term "mild cognitive impairment" was adopted by Petersen in 2004 to describe a period in the course of neurodegenerative disease where cognition is no longer normal relative to age expectations, however, daily functions are not sufficiently disrupted to correlate with the diagnosis of dementia. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of AD. The rate of conversion from amnestic form of MCI to AD is estimated to reach 10-15% per year. That is why MCI generated a great deal of research. When considering MCI a precursor of AD, it seems reasonable to study AD genetic markers in the MCI patients. In AD, association studies focus on genetic polymorphisms assumed to have an effect on the expression and modulation function of genes associated with AD pathogenesis (ApoE, APP, presenilin 1, presenilin 2, tau protein), and on polymorphisms related to metabolism of the aforementioned proteins (splicing, degradation). Neuropsychological assesment plays a substantial role in the diagnosis of MCI, especially in the case of identification of different MCI subtypes or typical profiles of cognitive performance in prodromal phases of neurodegenerative diseases. The optimal composition of diet may increase an average age and prevent impairment of cognitive functions at the same time. Despite the progress in early diagnosis of MCI and dementia, further research is needed on differential diagnosis and treatment. In amnestic subtype of MCI some genetic markers may already be present, predicting possible future development of AD. Pointing to the need of secondary prevention, lifestyle modifications and possible early treatment could be implemented.

Needs of Hospitalized Schizophrenic Patients in the North Moravia and the Czech Part of Silesia.

OBJECTIVES: The main aim of the study was to investigate the physiological and social needs of patients hospitalized with schizophrenia to uncover potential issues in these areas. METHODS: The relevant self-evaluating CANSAS questionnaire for physiological and social needs was used by nurses in a cohort of hospitalized schizophrenic patients undergoing rehabilitation before discharge from the mental hospital. RESULTS: Two hundred and forty-four patients (women N = 115) aged 18-58 years were involved in the study. Intimate relations, financial matters, treatment of psychotic symptoms, and sexual life were among the most pressing physiological and social needs in our study subjects. CONCLUSION: The results of our study should stimulate psychiatric nurses in their effort not only to detect but also address the problems of schizophrenic patients concerning unfulfilled needs.

Is microvascular abnormality a new endophenotype in schizophrenia?

BACKGROUND: A new method of assessment of microvascular abnormality in living schizophrenic subjects via retinal imaging was described by Meier et al. (2013). The principal aim of this review is to summarise the relevant knowledge and suggest further avenues of research into this topic. SUBJECT AND METHODS: On 20th April 2015, we carried out a search using the computer database system PubMed by using keywords "microvascular AND schizophrenia". RESULTS: Out of the 17 articles found, only seven were relevant. They are generally consistent with the hypothesis of microvascular pathology and brain inflammation as part of the pathogenesis in schizophrenia. It is important to stress that all studies of brain microvasculature in schizophrenia to date have been post mortem findings, apart from the work by Meier et al. (2013) which is related to retinal imaging in living subjects. CONCLUSIONS: Based on the literature, we suggest the following research and clinical avenues: Firstly, to assess whether microvascular abnormality found via retinal imaging, fulfils the criteria for the schizophrenia endophenotype. Secondly, to examine retinal imaging in high-risk individuals for schizophrenia. Thirdly, to determine whether the fMRI findings and cognitive abilities of schizophrenia patients in both longitudinal as well as cross-sectional studies, is associated with the microvascular abnormalities assessed by the retinal imaging. Fourthly, to determine if there is a correlation between microvascular retinal pathology and the positive or negative schizophrenia symptoms. Furthermore, to determine if childhood maltreatment results in any abnormities in retinal imaging. Lastly, to analyse the genetic background of schizophrenia retinal microvascular pathology and to apply anti-inflammatory agents in the treatment and prevention of schizophrenia if brain vasculitis is confirmed.

The dynamics of haemostatic parameters in acute psychotic patients: a one-year prospective study.

BACKGROUND: The primary goal of the present study was to replicate our previous finding of increased coagulation and thrombocytes activity in drug-naïve psychotic patients in comparison with healthy controls and ascertain whether the blood levels of thrombogenesis markers further increase over the course of a consecutive one-year antipsychotic treatment. SUBJECTS AND METHODS: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of nineteen men and seventeen women with acute psychosis (age 28.1±8.0 years, body mass index 22.6±4.2), and thirty-seven healthy volunteers matched for age, gender and body mass index. In the patient group, we repeated these assessments after three months and again after one year of antipsychotic treatment. RESULTS: D-dimers (median 0.38 versus 0.19 mg/l; p=0.00008), factor VIII (median 141.5% versus 110%; p=0.02) and sP-selectin (median 183.6 versus 112.4 ng/ml; p=0.00005) plasma levels were significantly increased in the group of patients with acute psychosis prior to treatment compared with healthy volunteers. The plasma levels of sP-selectin varied significantly (p=0.016) in the course of the one-year antipsychotic treatment, mainly between 3 and 6 months after start of therapy. The plasma levels of D-dimers and factor VIII did not change significantly, D-dimers remained elevated in contrast to the healthy controls. CONCLUSIONS: Patients with acute psychosis had increased levels of markers of thrombogenesis in comparison to the healthy volunteers. The haemostatic parameters also remained elevated during the one-year antipsychotic treatment.

Retinal microvascular abnormalities in major depression.

BACKGROUND: The aim of our study was to find a possible association between retinal microvascular abnormality and major depression in a non-geriatric population. METHOD: The participants with major depression were hospitalised at the University Hospital in Hradec Kralove, Department of Psychiatry. Retinal images were obtained using a stationary Fundus camera FF450 by Zeiss and a hand-held camera by oDocs. RESULTS: Fifty patients (men n=18, women n=32) aged 16 to 55 (men's average age 33.7±9.9 years, women's average age 37.9±11.5 years) were compared with fifty mentally healthy subjects (men n=28, women n=22) aged 18 to 61 (men's average age 35.3±9.2 years, women's average age 36.6±10.6 years) in a cross-sectional design. The patients were diagnosed with a single depressive episode (n=26) or a recurrent depressive disorder (n=24) according to the ICD-10 classification. Our results confirmed significant microvascular changes in the retina in patients with depressive disorder in comparison to the control group of mentally healthy subjects, with significantly larger arteriolar (P<0.0001) as well as venular (P<0.001-0.0001) calibres in major depression. CONCLUSION: According to the literature, acute and chronic neuroinflammation is associated with changes in microvascular form and function. The endothelium becomes a major participant in the inflammatory response damaging the surrounding tissue and its function. Because the retina and brain tissue share a common embryonic origin, we suspect similar microvascular pathology in the retina and in the brain in major depression. Our results may contribute to a better understanding of depression etiopathogenesis and to its personalized treatment.

Environmental Factors in the Etiology of Mental Disorders in the Czech Republic.

Background: Both genetic and environmental factors are important in etiology of mental disorders. Calculating polyenviromic risk/protective scores provides an updated perspective in research on the environmental causes of psychiatric disorders. We aimed to compare environmental risk and protective factors in patients with psychosis or a mood disorder (PSYCH+MOOD) and those with an anxiety disorder (ANX). Methods: We administered the internationally accepted questionnaire from the EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study, enriched with mood and anxiety disorder-relevant measures, to patients at two large university hospitals in the Czech Republic. Results: Ninety-four PSYCH+MOOD patients (average age 42.5 years; 46 males) and 52 ANX patients (average age 47.2 years; 17 males) participated. Neither polyenviromic risk score nor polyenviromic protective score differed significantly between PSYCH+MOOD and ANX groups (p = 0.149; p = 0.466, respectively). Conclusion: Scientific validity of the polyenviromic risk/protective score construct must still be demonstrated in large psychiatric samples, ideally in prospective studies. Nevertheless, researchers have already started to investigate environmental factors in the etiology of mental disorders in their complexity, similarly to polygenic risk scores.

Widened retinal arteriolar and venular diameters are not an endophenotype of schizophrenia: A one-time cross-sectional study.

OBJECTIVES: Studies of schizophrenia endophenotypes may help clinicians better understand the etiopathogenesis and treatment of this mental disorder. The aim of the study was to determine if retinal arteriolar or venular abnormalities are an endophenotype of schizophrenia. DESIGN: We performed a one-time cross-sectional study. MATERIALS AND METHODS: We enlisted schizophrenic patients (n = 53) hospitalized in the Department of Psychiatry, University Hospital Hradec Kralove; their mentally healthy first-degree relatives (n = 53); and unrelated, age- and sex-matched mentally healthy controls (n = 49). We recorded all participants´ sociodemographic and, if relevant, clinical variables. Retinal imaging was carried out using a digital fundus camera (FF450 + IR). Outcomes included retinal vessel calibers measured using the software application VAMPIRE. RESULTS: The study enrolled fifty-three schizophrenic patients (average age 32.1 years; males n = 38), an equal number of healthy relatives (average age 47.3 years; males n = 18), and forty-nine unrelated healthy controls (average age 32.2 years; males n = 35). Patients with schizophrenia had significantly increased retinal arteriolar diameters when compared to unrelated healthy controls (left eye p = 0.003; right eye p = 0.011) but not when compared to healthy relatives. The sizes of the retinal venules were not significantly different among the study groups. CONCLUSIONS: Our cross-sectional findings do not support the notion that retinal microvascular anomalies are an endophenotype in schizophrenia. Longitudinal studies of this subject should be included in further research.

Genomic copy number variations: A breakthrough in our knowledge on schizophrenia etiology?

OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence with a magnitude of 1 kb at least which is differently represented among individuals based on its deletion or duplication. Since 2008, multiple studies have reported copy number variations in schizophrenia, and they seem to fill in a gap in our knowledge on the genetic background of schizophrenia. The aim of this review is to sum up the current findings related to CNVs in schizophrenia in order to facilitate further research. METHODS: We searched the PubMed computer database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out of 91 obtained results, we selected the references based on their relevance. RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1 and 22q11.2 were associated with schizophrenia most frequently. The data provide evidence for low prevalent, but highly penetrant CNVs associated with schizophrenia. CNV deletions show higher penetrance than duplications. Larger CNVs often have higher penetrance than smaller CNVs. Although the vast majority of CNVs are inherited, CNVs that have newly occurred as de novo mutations have more readily been implicated in schizophrenia. De novo CNVs may be responsible for the presence of schizophrenia in only one of the two monozygotic twins, who otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia can lead to changes in the treatment and genetic counselling. Our knowledge on the genetic background of neurodevelopmental disorders may also reduce stigma in schizophrenia.

Genome-wide association studies in schizophrenia, and potential etiological and functional implications of their results.

BACKGROUND: Despite the fact that the genetic basis of schizophrenia has been intensively studied for more than two decades, our contemporary knowledge in this field is rather fractional, and a substantial part of it is still missing. The aim of this review article is to sum up the data coming from genome-wide association genetic studies in schizophrenia, and indicate prospective directions of further scientific endeavour. METHODS: We searched the National Human Genome Research Institute's Catalog of genome-wide association studies for schizophrenia to identify all papers related to this topic. In consequence, we looked up the possible relevancy of these findings for etiology and pathogenesis of schizophrenia using the computer gene and PubMed databases. RESULTS: Eighteen genome-wide association studies in schizophrenia have been published till now, referring to fifty-seven genes supposedly involved into schizophrenia's etiopathogenesis. Most of these genes are related to neurodevelopment, neuroendocrinology, and immunology. CONCLUSIONS: It is reasonable to predict that complex studies of sufficiently large samples, involving detection of copy number variants and assessment of endophenotypes, will produce definitive discoveries of genetic risk factors for schizophrenia in the future.

Comparison of Wisconsin Card Sorting Test results between Czech subjects dependent on methamphetamine versus healthy volunteers.

BACKGROUND: Methamphetamine is a neurotoxic agent. Its chronic abuse may result in cognitive impairment with negative consequences for patients' treatment and rehabilitation. The aim of the study was to compare Wisconsin Card Sorting Test profiles of Czech subjects dependent on methamphetamine with healthy individuals. SUBJECTS AND METHODS: Forty-three hospitalized Czech Caucasian patients including twenty-seven men at the average age of 25.3±5.2 years dependent on methamphetamine for 6.2±3.3 years were assessed by the Wisconsin Card Sorting Test. We used the same neurocognitive test for the comparison group of healthy controls with the same ethnicity (N=52, men N=28, average age of 38.7±12.1 years). We applied the Chi-Square Test, Two-Sample T Test, Mann-Whitney U Test and Kolmogorov-Smirnov Test to compare methamphetamine dependent patients with healthy volunteers. RESULTS: All recorded Wisconsin Card Sorting Test parameters were significantly different in the group of methamphetamine dependent patients versus healthy volunteers (P=0.04-0.006; Mann-Whitney U Test, Two-Sample T Test). The results showed a higher error rate and a smaller achievement quality in the patients as against healthy subjects. We ascertained a significant cognitive deterioration in the patients as compared to healthy volunteers even if the average patients' achievements were in the normal range according to the test norms. CONCLUSIONS: A cognitive impairment was present in the group of patients as compared to healthy controls. Better understanding of neurocognitive symptoms in methamphetamine dependent subjects should help to generate modern therapeutic approaches, both pharmacological and psychosocial, to prevent or attenuate the long-term negative consequences of methamphetamine use disorders.

Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.

BACKGROUND: Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication. METHODS: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index. RESULTS: D-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers. CONCLUSIONS: The results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence.

OBJECTIVES: About 25,000 serious methamphetamine abusers live in the Czech Republic among the total population of 10 million. Dependence on methamphetamine is markedly related to the brain neurotransmitter dopamine, metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country. METHODS: One hundred and twenty-three subjects dependent on methamphetamine (women N=44), parents of sixty-seven dependent individuals, and four hundred healthy controls (women N=250) were involved into the study. We performed a population-based as well as family-based genetic association studies. RESULTS: We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence using the population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED program, Version 3.1.4, respectively). We found a trend toward a statistically significant difference between the Val allele carriers and Met/Met homozygotes in the frequence of psychotic symptoms induced by methamphetamine (more frequent in Val carriers; p=0.062; Chi-Square Test). CONCLUSION: Further research involving haplotype analysis and other dopamine-related genetic polymorphisms in large populations is needed. More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence.

Gene-Environment Interactions in Major Mental Disorders in the Czech Republic.

BACKGROUND: Mental disorders affect about one-third of the human population, are typically chronic and significantly decrease the quality of life. Presently, the treatment of mental illnesses is far from adequate with a substantial proportion of the patients being pharmacoresistant and suffering from relapses. One of the reasons for this complicated situation is that we do not precisely know about the causes of mental disorders, so their treatment cannot be causal. The etiology of a mental disorder is typically based on a combination of molecular (genetic) and environmental factors. AIM: The aim of the project is to discover the gene-environment interactions (GxE) in a wide spectrum of mental disorders. METHODS: The design of our study is innovative in the sense that we intend to study large groups of associated mental disorders as a whole instead of in isolation. This would enable us to map out the possible environmental causal factors in detail in relation to their character, magnitude and timing. The project also allows a study of genetics (including epigenetics and microbiomes) as well as the environment simultaneously. We plan on involving three study groups: the first group are patients suffering from schizophrenia or a mood disorder such as major depression, recurrent depressive disorder and bipolar affective disorder; the second group of patients have anxiety disorders; and the third group are healthy volunteers from the general population who are genetically unrelated. All of the study subjects will undergo the following assessments: a psychiatric examination, the identification of stressful life events with the aid of a questionnaire, the examination of their reaction to stress, genetic and epigenetic (microRNA) assessments and the analysis of oral and gut microbiome. CONCLUSION: We expect that some of the genetic as well as environmental factors in the studied mental disorders are shared, while some others are specific. We also expect that the GxE (gene-environment interaction) in schizophrenic and affective disorders will be different from the GxE in anxiety disorders and that the GxE in the studied mental disorders will differ generally from the GxE in healthy volunteers. Our results can help in the prevention and individualized treatment of a range of mental disorders.

Four cases of venous thromboembolism associated with olanzapine.

AIMS: Psychiatric disorders and treatment with conventional antipsychotic medications have been associated with venous thromboembolism, but only a few data on recent antipsychotics such as olanzapine are available. METHODS: We describe four subjects treated with olanzapine who developed venous thromboembolism, and were hospitalized at the University Hospital in Hradec Kralove during the period 2004-2006. RESULTS: We found a combination of several clinical and laboratory risk factors in our patients. CONCLUSIONS: A cohort study or case-control studies are needed to better elucidate the possible role of olanzapine in etiopathogenesis of venous thromboembolism.

Repeated occurrence of clozapine-induced myocarditis in a patient with schizoaffective disorder and comorbid Parkinson's disease.

Myocarditis is a rare but life threatening adverse effect of clozapine. Some symptoms of myocarditis--elevated temperature, tachycardia and fatigue--appear commonly during the onset of treatment with clozapine and during the dose titration. We present a case of a patient with concurrent schizoaffective disorder and Parkinson's disease, who twice developed clozapine-induced myocarditis. All symptoms disappeared after the discontinuation of the drug. Early diagnosis, discontinuation of clozapine and supportive therapy of myocarditis lower the risk of a fatal outcome.