Aldosterone and aldosterone/cortisol ratio is higher in serum of long-term compared to first episode schizophrenia patients: A pilot study.

We have previously shown that patients with severe depressive episode exhibit higher aldosterone concentrations compared to those with moderate depressive episode. The present study was undertaken to test the hypothesis that circulating concentration of aldosterone reflect the clinical state in patients with schizophrenia. The sample consisted of 36 hospitalized patients (25 men, 11 women) with the first episode or long-term course of schizophrenia. The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS). Samples for measurement of serum aldosterone were obtained immediately after awakening. The results showed that serum aldosterone concentrations were lower in patients with the first episode compared to those in patients with long-term course of schizophrenia. Importantly, lower aldosterone concentrations observed in patients with the first episode were associated with more severe clinical symptoms as indicated by all subscales of PANSS. Serum cortisol concentrations did not differ between the groups, while the aldosterone/cortisol ratio showed similar pattern as aldosterone concentrations. The present pilot study suggests that circulating aldosterone in patients with schizophrenia may reflect the severity of clinical symptoms but in an opposite direction than in patients with major depressive disorder.

[Compliance in psychiatry]. / Kompliance v psychiatrii.

In the first place for economic reasons the compliance is a great problem in all branches of clinical medicine. In psychiatric patients the compliance is lower than in somatically ill patients. It plays an important role especially in severe psychotic disorders, e.g. in affective and schizophrenic disorders. The low compliance in schizophrenia is associated with a higher risk of relapses, which have an unfavourable influence on the course of illness. Compliance can be improved mainly by influencing the factors associated with the treatment. The doctors can choose the optimal drug on the base of their knowledge about psychopharmacotherapeutic possibilities and information about patient. Nowadays we have at our disposal atypical antipsychotics, which are subjectively better tolerated and are available in different formulations. In comparison with typical antipsychotics there are advantages especially with long-term treatment.

[Hippocampus, structure of the brain and schizophrenia]. / Hipokampus, morfologie mozku a schizofrenie.

Schizophrenia is a clinically heterogeneous state without clearly defined pathogenesis. This limits the classification approaches with consequent lack of ability for individual treatment strategies. It becomes evident that hippocampus is a key structure in the neuropathology of schizophrenia and a concept of hippocampal reduction as an endophenotype of schizophrenia was established. The biggest support came from MRI volumetric studies. Despite that, due to some inconsistent findings, clinical consequences of hippocampal shrinkage are not yet clear. Contemporary methods of brain imaging (computation morphometry, voxel-based morphometry) could help us to outline the concept of schizophrenia and to clarify the clinical consequences of brain structure changes.

[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation]. / Mutacní analáza LQT genu u jedincu s polékovým prodlouzením QT intervalu.

BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome). RESULTS: At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature). CONCLUSION: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.

[Depressive disorder in cardiovascular, neurological and oncologic diseases]. / Deprese u kardiálních, neurologických a onkologický onemocnení.

The discovery of antidepressants meant undoubtedly a revolution in psychiatry. The development of antidepressants has changed the image of psychiatry, brought a progress in the treatment and became a stimulus for investigations of mental illnesses ethiopathogenesis. Nowadays it is becoming evident, that many biologic, psychologic and with high probability also social aspects are common for the depression and for somatic disorders. The more prominent is the association of depression with cardiovascular disease. Neurological disease, mainly the epilepsy, Parkinson disease an stroke represent further common sphere. Historically, association between cancer and depression was identified first. The article presents epidemiological data and analyses possible common mechanisms of somatic disease and depression. In the last part the actual data about the treatment of depression in individual somatic diseases are described.

[Cognitive dysfunction and its therapy]. / Kognitivní dysfunkce a její lécba--výzva pro 21. století.

In the first part the meaning of terms cognition and cognitive dysfunction is clarified. Cognitive dysfunction is found in many neuropsychiatric disorders. Majority of studies were done in patients with schizophrenia and dementia. For studying cognitive dysfunction, the most appropriate appear the initial phases of the disease. The next part of the study summarizes the treatment possibilities of cognitive dysfunction in schizophrenia. Atypical antipsychotics represent the basal treatment. The improvement of cognitive deficit by atypical antipsychotics is significant, but its importance in real life is small. The new add-on treatment has the potential for further improvement of cognitive dysfunction. This approach includes augmenting effects of neurotransmitters related to cognition (glutamate, noradrenalin, serotonin, acetylcholine). The improvement of cognitive dysfunction can improve the long-term outcome and functional prognosis in patients suffering from schizophrenic disorder.

[Present status and future of imaging methods in neuropsychiatry]. / Soucasnost a budoucnost zobrazovacích metod v neuropsychiatrii.

Introduction describes historical relations between neurology and psychiatry. Both disciplines are now much nearer to each other than before--they have received similar diagnostic tools and they have similar therapeutic methods. Psychiatry is considered to be an integral part of neuroscience. The article reviews findings on the structural and functional changes accompanying the most serious psychiatric diseases and the growing role of the brain imaging methods is depicted.

[Psychiatric problems in internal practice. Part I]. / Psychiatrická problematika v interní praxi I. cást.

Review deals with depression, which frequently occurs in patients with cardiovascular disease. Along with that, cardiovascular complications are frequent cause of the high morbidity and mortality of depressed patients. Several common ethiopathogenic factors can be identified (endocrine changes, immunity alteration, structure of personality, life style). Diagnose of depression in somatically diseased patients may be difficult to set; however, it is necessary to consider it. Some conjoint treatment approaches are possible. For the use in the internal medicine new antidepression drugs with lower affects on the cardiovascular system appear promising. Mutual collaboration in the clinical praxis is highly desirable.

The changes of biological markers and treatment efficacy in schizophrenia.

1. In a group of schizophrenic patients, the effect and selected parameters of biological markers were evaluated during the index hospitalisation in the acute phase of schizophrenia (n = 30) and then after one year of ambulatory treatment. 2. During the acute treatment, a significant drop in symptomatology was recorded in average; an analogical tendency was observed further on, too. Apart from that, a significant change was observed in 5/41 parameters being monitored (the pair t-test): I) decrease in the total NES score, II) decrease in the sensorial integration subscale NES score, III) increase in psychomotor speed, IV) decrease in auditory reaction time, V) increase in basal cortisol. 3. In the comparison of the successfully (severity of illness after one year = 1, 2) and unsuccessfully (severity of illness after one year > or =3) treated patients in the beginning of treatment in the acute phase, the unsuccessful group had a significantly higher score of negative symptomatology, and by the end of the acute treatment, again, a significantly higher score of negative symptomatology, a higher total PANSS score and a greater severity of illness. 4. In the acute phase, the successful group had a significantly better score in individual items of the Contemporary Memory Scale and a significantly worse performance and goal-aimed concentration in the Bourdon test than the unsuccessfully treated one; apart from that, it had a significantly higher cortisol level after dexamethasone, which was also reflected in the lower percentage rate of dexamethasone nonsupression. 5. In the course of the year, a drop in the total NES score for the individual subscales occurred; a significant drop was observed in the sensory integration subscale. The worse concentration items improved significantly in the successful group in contrast to the unsuccessful group, where they showed a downgrade tendency. Changes in Contemporary Memory Scale were negligible and mostly below statistical significance. Apart from that, a drop in basal cortisolemia occurred in the successful group and an increase in cortisolemia after administering dexamethasone was registered in the unsuccessful group. 6. The more successful group had a significantly lower NES score, a significantly better visual reaction time and a smaller forgetting item (in percentiles) after the one-year period.

Effects of psychopharmacotherapy on phenotypic expression of cytochrome P450 2D6 in patients genotyped for CYP2D6 mutations.

No Abstract

[Psychiatry and the neurosciences]. / Psychiatrie a neurovedy.

The author draws attention to the importance of the development of neurosciences for psychiatry in particular for studies of biological aspects of mental disorders. She presents a review of methods which contribute to research of biological markers. Sufficiently sensitive and specific biological markers will contribute to the elucidation of the etiopathogenesis, objective diagnostics and prediction of the effectiveness of treatment. Emphatic enforcement of new findings into clinical practice will contribute to a more favourable position of psychiatry within the framework of medicine and society.

Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation in patients with schizophrenia and major depression.

Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation phenotypes were determined in 115 Czech drug-free in-patients with schizophrenia (n = 64) or major depressive disorder (n = 51). These data were compared with a control group of 321 healthy volunteers from the North-East German area of Greifswald. The distribution of debrisoquine hydroxylator phenotypes was almost identical in patients and healthy controls. Thus, there were 8.7% (95% CI 5.4-12.0%) of poor metabolizers (PM) among patients while 8.7% (95% CI 23.6-13.8%) PM among the control group. The prevalences of PM amongst patients with chronic schizophrenia and major depression were 10.9% (95% CI 4.5-21.3%) and 5.9% (95% CI 1.24-16.3%), respectively (chi 2 schizophrenics vs control = 0.315, NS; chi 2 depressive patients vs control = 0.450, NS). However, within the group of EM patients there was a significant (P < 0.01) shift towards higher debrisoquine metabolic ratios, reflecting a lower hydroxylation capacity in EM patients compared with EM healthy controls. The proportion of slow acetylators (SA) was 60.0% (95% CI 51.0-68.9%) in the entire group of psychiatric patients and 57.5% (95% CI 52.1-62.9%) in the control group (chi 2 all patients vs control = 0.195, NS). Furthermore, there were no significant differences in the prevalence of the SA phenotype between controls and schizophrenics or patients with major depression. Although the results of this modest study were negative, the presence of subtle differences in the metabolic capacity between psychiatric patients and a healthy population cannot be ruled out.

[Efficacy and tolerance of risperidone in various doses (report of a study)]. / Ucinnost a snásenlivost risperidonu pri ruzném dávkování (sdelení z praxe).

Risperidone was compared in 2 double blind studies with haloperidol and perphenazine in schizophrenic psychoses. According to the maximal daily dose achieved the risperidone group was divided in 4 subgroups and the risperidone efficacy and tolerability in these groups were compared both mutually and in relation to the baseline. With all doses a good global antipsychotic efficacy has been observed. There were no statistically significant differences in influencing of productive or negative symptoms with exception of significantly more pronounced reduction of productive catatonic symptoms with 2 < max < or = 5 mg in comparison with doses higher than 15 mg daily. Extrapyramidal symptoms were less frequent with lower doses: with 2 < max < or = 5 mg significantly lower occurrence of increased muscle tonus and tremor was found than with higher doses. With maximal daily doses above 10 mg antiparkinson drugs had to be applied in more patients and in the case of trihexyphenidyl this difference reached a statistically significant level.

[Effectiveness of clonazepam in depressive disorders]. / Ucinnost clonazepamu v indikaci depresívní poruchy.

Clonazepam was administered to 55 patients with depressive disorder (DSM-III-R) in average minimal and maximal doses of 2.40 and 6.54 mg/day for 21-28 days. Complete remission was achieved in 60% patients (Serejskij AB, drop of global HAMD and FKD score by more than 50%), in particular in case of concurrent anxiety. A marked antidepressive effectiveness of clonazepam was suggested also by a drop of the total HAMD and FKD score already after the first week of treatment. All items of the HAMD and FKD scale were significantly positively influenced with the exception of agitation, somatic anxiety, insight, paranoidity, obsession respectively hypochondriasis and paranoidity. No correlation was found between the effect of clonazepam and sex, the patients' age, duration of the depressive disorder, period of the index episode and severity of depression. As to undesirable effects, the authors recorded fatigue and sleepiness (40%) and hypotension (20% of the patients), in particular at the onset of treatment and after larger daily doses. In 3/10 bipolar patients a switch to hypomania was observed.

[Plasma levels of clozapine]. / Plazmatické hladiny clozapinu.

At the beginning some rules and conclusions concerning neuroleptic blood levels are mentioned. Clozapine blood levels are discussed in a more detailed way. A survey of the most important studies about the relation between therapeutic effect and blood levels of clozapine is given. Finally, the author presents his own experience with blood levels of clozapine in patients on maintenance treatment with the aim to find the lowest effective dose.

[Paroxetine in the treatment of depressive disorders (pilot study)]. / Paroxetin v lécbe depresívních poruch. (Pilotní studie).

In an open study, 42 depressive patients (according to DSM-III-R) were administered paroxetine at mean minimal and maximum doses of 21 and 48 mg once daily in the morning. Treatment resulted in complete remission as defined by Serejsky in 57%, and 55% of patients were rated, according to CGI, as improved. Global HAMD and FKD scores significantly dropped compared to baseline values and responders and non-responders differed significantly as early as seven days of treatment, although the onset of the antidepressive effect was not clinically apparent before 2 weeks of treatment. Significant reductions were seen in all items except paranoidity and weight loss and hypochondria using the FKD scale. A substantial reduction in suicidal ideation and tendencies was also noted in the group of non-responders, a finding supporting a non-specific anti-suicidal effect of paroxetine, which was therapeutically significantly more successful in women than in men. Side effects occurring in 10% and more percent of treated subjects included fatiguability, sweating, tremor, dry mouth, obstipation and nausea.

[75 years of the University Psychiatric Clinic in Brno]. / 75 let trvání univerzitní psychiatrické kliniky v Brne.

The University Psychiatric Clinic in Brno celebrated its 75th anniversary as part of the 75th jubilee of Masaryk University. At this occasion the author reminds briefly of its history and present activities. Teaching activities research and therapeutic and preventive care are reviewed.