Steroid hormones in the development of postpartum depression.

Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period around spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chromatography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already the changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that changes in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to postpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period.

Polymorphisms of genes for brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase in depression and metabolic syndrome.

The prevalence of metabolic syndrome as well as the occurrence of depressive disorder, which are both connected with increased risk of diabetes mellitus type 2 and cardiovascular diseases, is continually increasing worldwide. These disorders are interconnected at various levels; the genetic one seems to be promising. Contribution of genetic factors to the aetiopathogenesis of depressive disorder weighs within the range 40-50 %, whereas the genetic background for the manifestation of metabolic syndrome is more complicated. In this pilot study, we investigated the incidence of polymorphisms in several genes supposed to play a role in the development of both depressive disorder and metabolic syndrome such as brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase. The entire group consisted of 42 patients with depressive disorder, 57 probands with metabolic syndrome and 41 control individuals. We found that genotype Met/Met of the Val66Met polymorphism of the brain-derived neurotrophic factor gene was positively associated with depressive disorder (P < 0.05), but we were not able to find any significant associations of both the depressive disorder and metabolic syndrome with the remaining polymorphisms studied (methylenetetrahydrofolate reductase 677CT, methylenetet rahydrofolate reductase 1298AC, endothelial nitric oxide synthase Glu298Asp, and tyrosine hydroxylase).

[Features of metabolic syndrome in patients with depressive disorder]. / Rysy metabolického syndromu u nemocných s depresivní poruchou.

BACKGROUND: Depressive disorder is a serious illness with a high incidence, proxime accessit after anxiety disorders among the psychiatric diseases. It is accompanied by an increased risk of development of type 2 diabetes mellitus, cardiovascular disease, and by increased all-cause mortality. Recently published data have suggested that factors connected with the insulin resistance are at the background of this association. METHODS AND RESULTS: In this pilot study we have investigated parameters of lipid metabolism and glucose homeostasis in consecutively admitted patients suffering from depressive disorder (DD) (group of 42 people), in 57 patients with the metabolic syndrome (MetS) and in a control group of 49 apparently healthy persons (CON). Depressive patients did not differ from the control group by age or body mass index (BMI) value, but they had statistically significantly higher concentrations of serum insulin, C-peptide, glucose, triglycerides (TG), conjugated dienes in LDL particles (CD-LDL), higher value of microalbuminuria and of insulin resistance (HOMA-IR) index. They simultaneously had significantly lower value of the insulin sensitivity (QUICKI) index. In comparison with the MetS group the depressive patients were characterized by significantly lower both systolic and diastolic blood pressure, BMI , serum TG, apolipoprotein B, uric acid, C-peptide and by higher concentrations of apolipoprotein A-I and HDL-cholesterol. On the contrary, we have not found statistically significant differences between the DD and MetS groups in the concentrations of serum insulin, glucose, HOMA and QUICKI indices, in CD-LDL and MAU. CONCLUSIONS: In this pilot study, we have found in patients with depressive disorder certain features of metabolic syndrome, especially insulin resistance and oxidative stress.

[Metabolic syndrome and depression--clinical relations]. / Metabolický syndrom a deprese--klinické vztahy.

The occurrence of both obesity and type 2 diabetes mellitus is rapidly increasing; according to WHO data, this can be considered as a worldwide epidemic. The obesity is one of the components of metabolic syndrome, the cluster of several risk factors of atherosclerosis such as dyslipidemia, hypertension, impaired glucose homeostasis, pro-thrombotic state and subclinical inflammation. The importance of the metabolic syndrome is confirmed by findings of the several times increased risk of both the type 2 diabetes mellitus and cardiovascular disease. Similarly, as in the case of obesity and diabetes, the incidence and prevalence of depressive disorder are still increasing and depressive disorder belongs to the most important causes of disability. The interrelations between depressive disorder and diabetes are known for a long time. Diabetics very often suffer from depression and vice versa, the depressive disorder is a significant risk factor of type 2 diabetes mellitus development and worsens the survival of diabetics. Those relationships have been recently intensively studied. Our paper reviews genetic, nutritional, metabolic and hormonal factors, contributing to the above mentioned syndrome.

Alterations in calcium homeostasis as biological marker for mild Alzheimer's disease?

The calcium hypothesis of neurodegenerative disorders such as Alzheimer's disease (AD) suggests that altered cytosolic Ca(2+) levels ( Ca(2+) (i)) and/or disturbances in Ca2+ homeostasis concern cellular mechanisms underlying neuronal pathology. To search for a diagnostic marker of Alzheimer's disease, we measured cytosolic calcium concentrations in platelets of AD patients, age-matched control subjects (AMC), and vascular dementia (VD) patients. The ( Ca(2+) (i)) was determined using long wavelength indicator Fluo-3AM in 21 mild AD patients, 17 AMC, and 23 patients with VD. The basal values of [Ca(2+)](i) were significantly lower in AD compared to AMC. After the addition of 1 mM calcium, the [Ca(2+)](i) markedly increased in platelets of AD compared to AMC and VD. Measurement of calcium homeostasis could provide a very sensitive, but less specific biological marker of AD. These results support the hypothesis that influencing calcium homeostasis may provide a therapeutic strategy in dementia.

Cytosolic calcium alterations in platelets of patients with early stages of Alzheimer's disease.

Alterations in calcium homeostasis might be implicated in the neuropathology of Alzheimer's disease (AD). To date it is not clear whether changes in cytosolic calcium level ([Ca2+ ]i) are the result or the cause of pathogenic effects. In platelets of patients with early stages of AD, the basal values of [Ca2+]i in the absence of extracellular Ca2+ were significantly lower in comparison with age-matched and young controls. After the addition of 1 mM calcium into the incubation medium the [Ca2+]i markedly increased in platelets of AD patients whereas the increase only to a smaller extent was observed in control age-matched and young subjects. The present study proposes that calcium dysregulation during the whole disease period could not be uniform and according to our results the [Ca2+]i is reduced in the first stages of AD. We suggest that the disturbed calcium homeostasis in AD is an "early defect."

[Molecular genetic analysis of Alzheimer's dementia in the Czech population. The APP-717 mutation in the gene for amyloid protein precursor]. / Molekulárne genetická analýza Alzheimerovy demence v Ceské populaci. Mutace (APP-717) v genu pro amyloidní proteinový prekurzor (APP).

BACKGROUND: Although locus mutations in the gene for the amyloid precursor protein were already described in patients with Alzheimer's disease, there still are some patients where this mutation was not found and no link was found with other possible genetic loci on chromosomes 14 and 19. Therefore a group of subjects with Alzheimer's disease was subjected to tests for the presence of a mutation in the APP gene (in position 717). METHODS AND RESULTS: In a selected group of subjects with Alzheimer's disease (AD) in the gene for amyloid precursor protein in position 717 mutations of its transmembraneous region are found. The authors analyzed the genome DNA of cerebral tissue of Czech subjects for the presence of this mutation by means of the polymerase chain reaction with subsequent verification by sequencing analysis. In every subject genetic analyses from cerebral areas of the frontal lobe, temporal lobe, parietal lobe and hippocampus were performed. The methods used were the polymerase chain reaction (PCR) and sequencing. From the total number of 18 subjects with confirmed Alzheimer's disease and six non-related subjects without histopathological signs of Alzheimer's disease after the age of 90 years, three sequencing changes were found in position 717 of exon 17 of the transmembranous region of the precursor of beta-4 amyloid glycoprotein. In the first case it was substitution of thymin for adenine in codon 717, in the second case substitution of cytosine for thymine, in the third case a sporadic mutation of guanine for thymine in codon 717 was found. CONCLUSIONS: It was revealed that codon 717 could be a so-called hot spot site preferred for the preferential development of mutations in codon 717 in the gene for the amyloid precursor protein (APP).

"Epileptosis"--a syndrome or useless speculation?

102 patients were divided into 3 groups: epileptics, psychotics and epileptics with psychotic symptoms. All had long been monitored for a number of clinical and laboratory parameters. Though different in many respects, all share states of sudden dysphoria, cacophoria, panic anxiety, horror, and EEG (stereo-EEG, too) signs of epileptic or other gross anomalies, often correlated to those affective disorders. Attacks of dysphoria, epilepsy, and psychosis come spontaneously and in response to biological (hypoglycemia, sleep deprivation, alcohol, menses) or psychosocial stimulation (agitation, quarrels, fear of redundancy, psychic trauma). These states (attacks, dysphoria, "neurotic" or even psychotic episodes) often provoke one another. -Calling this syndrome epileptosis, we believe its mechanism is due to lesions of the limbic and brainstem modulation systems. At the start of the process there is an epileptic focus in the amygdalo-hippocampal complex (AHC) which in itself can trigger simple or complex partial paroxysm but also-by means of electric stimulation of the AHC-states of dysphoria, anxiety, and psychotic hallucinations. Besides, a form of pathological learning develops in premorbid "hypersensitive" personality which can be put down to associative learning and to Overton's phenomenon of "state-dependent retention of learned responses". This may give rise to mutual stimulation where epileptic focal activity in AHC can provoke dysphoria while an external psychosocial situation can trigger epileptic activity there, too (AHC). Since there need not always be mydriasis (though other vegetative signs such as tachycardia, tachypnoea, nausea, blush and others are frequent) or unconsciousness, and some psychomotor manifestations may be out of the ordinary, and scalp EEG may be normal, such patients are often regarded as "hysterics" or malingerers.

[A case of pathologic (F63.0) or dangerous (Z72.6) gambling?]. / Prípad patologického (F63.0) nebo hazardního (Z72.6) hrácství?

The authors recapitulate the term of pathological gambling in different classifications incl. the 10th revision of the ICD. It is a new concept which involves certain obscure points also from the linguistic aspect. They demonstrate on a forensic expert opinion elaborated by the Faculty why the statement of the accused that he committed extensive property offenses as a result of pathological gambling was not accepted by experts.

[Linkage analysis in pedigrees with Alzheimer's dementia]. / Vyuzití vazebné analýzy v rodokmenech s Alzheimerovou demencí.

Linkage analysis with three specific DNA markers was carried out on the Alzheimer's dementia pedigrees. The DNA markers used in our study, D21S1/D21S11, D21S13 and D21S16 in the 21q11.2-21q21 regions are localized. The results from different brain DNA samples and from peripheral blood samples of AD families were evaluated by two-point linkage analysis. The linkage between DNA markers and one AD pedigree was observed (D21S1/S11 and D21S13).

[Detection of cerebropathy in neurologic and psychiatric diseases]. / Prukaz cerebropatie u neurologických a psychiatrických chorob.

The authors made a comprehensive examination of 16 patients--epileptics, alcoholics, psychotic subjects and patients after cerebral contusion. The patients were subjected to a neurological, psychiatric, psychological examination as well as to a morphological examination (X-ray, CT, NMR), physiological examination (EEG, polysomnography, evoked potentials), immunological examination and SPECT. The majority of patients had positive CT and SPECT findings suggesting focal brain damage. These results could be explained only in exceptional cases by injury, the majority was of unknown aetiology. With this corresponded focal EEG abnormalities and in particular sleep disorders, sometimes subjective but always detectable by objective methods. There was always a shortage of REM, sometimes also NONREM sleep. Half the patients were subjected to an immunological examination which was always positive and comprised elevated acute stage proteins and proteins associated with the stress reaction. Numerous data in the literature and the authors' experience indicate that the mentioned pathological findings are not incidental and form, independently on the aetiology, an integrated unit for which the term cerebropathy can be used. A primary role is played by the epileptic focus and its quality, i.e. above all the rate of discharge and site and humoroergic systems of the brain stem, in particular their efficiency and mutual balance. The events have a programmed sequence. At the beginning an epileptic focus develops which influences the surrounding area, secondary and tertiary foci are formed and the thalamo-cortical system is affected. Soon this is followed by an apparent influence of the epileptic activity on structures of the brain-stem. The consequence are changes affecting sleep, mood, mental performance, immunity, endosecretion and paroxysms. Subsequently individual symptoms are already prepared but have a different latency of manifestation and the latter depends also on external provoking influences. The thalamo-cortical reaction is characterized by the manifestation of epileptic paroxysms and sets in after a different interindividual incubation following injury. The same applies to the hippocampal reaction manifested by the organic psychosyndrome. Some symptoms such as changes of immunity, sleep or endosecretory function are not necessarily manifested if the influence of the focus on structures of the brain-stem is not sufficiently intense. Conversely if the effect on the brain-stem and limbic structures is greater and the effect on the thalamo-cortical system smaller, psychotiform behaviour develops. Then there are marked changes of phoria, dynamogeny, rate, affectivity, sleep and hormonal secretion and its equilibrium.

Neurohumoral relations in neurological and psychiatric patients.

Sixteen patients-epileptics, alcoholics, psychotics and post-contusion cases-were subjected to neurological, psychiatric, psychological, morphological (X-ray, CT, NMR), physiological (EEG, polysomnography, evoked potentials), immunological and SPECT examination. Most had CT and SPECT signs of focal brain damage. The results were but exceptionally due to injury, most were of unknown etiology. This tallied with EEG focal abnormalities, mainly sleep disorders, sometimes subjective ones, but invariably detectable objectively. In each case there was REM, in some also NONREM sleep deficiency. Half of the cases were tested immunologically, each time with positive results: increased levels of acute-phase protein and stress-reaction proteins. As copious literature and our experience show, the above pathological condition, rather than being accidental, constitute regardless of etiology, an integrated entity which could be called "programme cerebropathy". The primary role is played there by the epileptic focus and its properties, in particular, the speed of discharge and localization and brain stem humoroergic systems, i.e., their performance and mutual balance. There is a program sequence of events, first, and epileptic focus acting on the neighborhood, the rise of secondary and tertiary foci, and influence over the thalamocortical system. Soon afterwards, epileptic activity begins to act on brain-stem structures. This results in changes in sleep, mood, psychic output, immunity, endosecretion, and in paroxysms.

[Creutzfeldt-Jakob disease as a cause or complication of senile dementia]. / Creutzfeldtova-Jakobova choroba jako prícina ci komplikace senilní demence.

Two observations of Creutzfeldt-Jakob disease, one typical, the other atypical, recorded in a brief series of consecutively examined brains of demented patients who died at psychiatric clinics suggest that this disease occurs more frequently in psychiatric departments. The authors deal with the standard clinical and neurohistological diagnosis and the differential diagnosis. As molecular biological techniques are becoming more widely available, these examinations should be made in cases of dementia with a "negative" neurohistological finding.

[Reliability of the Czech version of the GBS rating scale for dementia syndromes]. / Studie reliability ceské verze posuzovací stupnice GBS pro syndromy demence.

By the geriatric evaluation scale GBS for syndromes of dementia in a Czech translation 31 patients of the gerontopsychiatric department were evaluated. The reliability study was implemented by two psychiatrists. The authors compared the results of their own study with results of studies made in other countries. They found a high grade of reliability of the evaluation. They consider the definition of items on the scale and their evaluation practical and suited even for less trained observers or observers with a different training.

[Sulpiride in psychiatric practice]. / Sulpirid v psychiatrické praxi.

Sulpiride is a substituted benzamide which blocks selectively D-2 receptors. The authors tested its clinical effectiveness in schizophrenia, anorexia nervosa and bulimia nervosa. In schizophrenia its action was compared with that of haloperidol. It was revealed that sulpiride is an effective drug, in particular in schizophrenia with abulic and depressive symptoms without productive symptoms and in psychoaffective psychoses. In the treatment of anorexia nervosa and bulimia nervosa its therapeutic action was not superior to that of other preparations used in these diseases.