[The association between the serotonin receptor family and depression]. / A szerotonin receptorcsalád és a depresszió kapcsolata.

It is commonplace that depression is a heterogeneous mental disorder and this fact is the main driver of seek for aetiology and therapeutic opportunities. Selective serotonin reuptake inhibitors emerging in the 1980s are still among the most commonly prescribed medicines in the world. Due to their use, large groups of patients who previously remained untreated or treated at the cost of unwanted side effects of older antidepressants have chance to receive more optimal therapy. The background of the potential aetiology is multifaceted. However, we can point out that, according to the huge amount of data available, elements of the 5-HT system determine both directly and indirectly a number of emotional states, moods, stress responses, predispositions to affective diseases, and ultimately depression itself. In this article we review the role of relevant elements of the system and novelties in explanation of therapeutic mechanism.

[Professional identity of Hungarian psychiatrist. Experiences of a study]. / A magyar pszichiáter identitása. Egy tudományos felmérés tapasztalatai.

INTRODUCTION: A main determinant of professional identity is the integrity of the discipline. The complexity of psychiatry in biological, psychological and sociological aspects is a typical instance of the necessity for integration. AIM: Based on the bio-psycho-social dimensions and on their opinion about acceptance of psychiatry, we explored the professional identities of physicians working in Hungarian contemporary psychiatry. METHOD: Voluntary, anonymous responses were collected by using a 10-point evaluation scale on professional attitude, appreciation of psychiatry from lay society and other medical professions, and the importance of biology, psychology and sociology within psychiatry. RESULTS: The 228 respondents showed a highly significant effect of basic sciences: biology was the most relevant followed by psychology and sociology. Specialists in psychiatry (n = 171) showed a more marked preference for biology than the trainees, while specialists in psychotherapy (n = 74) considered the psychological component significantly more important than other respondents. The public acceptance of psychiatry was low as compared with other medical professions. CONCLUSIONS: The consistency between self-image and profession shows that the multidimensionality of psychiatry is not primarily an individual challenge. The impact on identity shows the key importance of education. Improving the prestige of psychiatry requires keeping our professional identity up-to-date, communicating with physicians with different preferences, and cooperating with other medical professions. Orv Hetil. 2018; 159(2): 58-63.

Continuous maintenance antipsychotic treatment in schizophrenia.

During recent years concerns have been raised about the long-term cumulative and potentially negative impact of continuous maintenance antipsychotic treatment of schizophrenia on the human body, especially on the central nervous system. This paper aims at providing a summary of literature data on continuous maintenance treatment for practicing physicians. The results show that continuous maintenance antipsychotic treatment can significantly decrease the risk of relapses and improve the long-term outcome in schizophrenia. Regarding the long-term effects of antipsychotic treatment on the central nervous system, however, further research is needed to answer the question: are brain morphological and functional changes associated with the disease or the treatment or both? 'Based on the data available, low antipsychotic doses are effective and safe while high doses of antipsychotics should be avoided. This review concludes that the minimum effective doses of antipsychotics should be administered for continuous maintenance treatment.

[The diagnosis and treatment of bipolar affective disorders].

No abstcarct available.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors.

The majority of our genes may be regulated in a daily rhythm, including the genes for cell cycle control. Epidemiological and genetic evidences suggest that disruption of circadian timing mechanisms makes our cells more vulnerable to cancer formation. The aim of this study was to investigate the relationship between expression patterns of circadian clock genes (period homolog (per)1, per2, clock, and cry1) and tumor development by analyzing human skin biopsies of malignant melanoma and nonmalignant naevus tumors. We found that mRNA levels and nuclear immunopositivity for the investigated clock genes were reduced by 30-60 % in both melanoma and in naevus biopsies if compared with adjacent nontumorous samples. The alterations in melanoma presented significant associations with clinicopathological characteristics (e.g., Breslow thickness). Contrary to previous reports, the moderate decrease of per1 expression seen in malignant tissues could not be linked to malignant transformation itself; rather, it reflects only the alterations in tissue composition. In turn, clock expression was upregulated in nontumorous cells of melanoma biopsies but not in melanoma cells or naevus cells. As this gene (clock) is closely related to cellular metabolism, our data suggest its role in the impaired regulation of metabolism in malignant tumors. Our results present the first clinical evidence for a possible link between circadian clock genes and human skin tumorigenesis.

Circadian clocks and tumor biology: what is to learn from human skin biopsies?

Some of the components of the circadian molecular clock have been shown to link directly to tumor suppression. Most studies on human tumorous biopsies with consistently down-regulated clock gene expression suggested a protective role for these genes against cancer formation. To highlight some limitations of this hypothesis we review these data in light of recent evidences from animal research, epidemiologic studies, and clinical data on skin tumors. We emphasize the role of circadian rhythmic orchestration in cellular metabolism with a potential in cancer development.

[From the surgical field to the microscope. A new tool to identify the lymph node specimens in oncologic surgery]. / A mutotol a mikroszkópig. A rendszerezett nyirokcsomóminták azonosításának új eszköze a ráksebészetben.

Oncologic surgery and pTNM staging require systemic removal of the locoregional lymphnodes. While the optimal extent and therapeutical and/or prognostic value of the lymphadenectomy/sampling are debated organ by organ and (sub)speciality by (sub)speciality, relevance of the lymphnode sytem-tumor concept itself is beyond doubt. Loss of information and existence of traps on the "surgical field-microscope" pathway is an international phenomenon, calling for solution. An integrated sterile and disposable lymphnode tray system is presented here for applications in the different fields of cancer surgery of the upper GI tract, retroperitoneum (gynecology, urology) and ear-nose-throat surgery.

A Real-World, Prospective, Multicenter, Single-Arm Observational Study of Duloxetine in Patients With Major Depressive Disorder or Generalized Anxiety Disorder.

Background: Suboptimal treatment response during anti-depressive treatment is fairly common with the first antidepressant (AD) choice, followed by switching to another agent in the majority of cases. However, the efficacy of this strategy over continuation of the original agent is less solidly documented in real-life studies. The aim of our present study was to ascertain the effects of switching to duloxetine following inadequate response to prior ADs on general illness severity, pain, and health-related quality of life in a large sample of major depressive disorder (MDD) and generalized anxiety disorder (GAD) patients in a prospective, real-world, multicenter, observational study. Methods: A total of 578 participants with MDD or GAD were enrolled in 58 outpatient sites in an 8-week, single-arm, open-label, flexible-dose trial with duloxetine. Severity of symptoms [with Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I)], severity of pain (with a Visual Analog Scale), satisfaction with current treatment, and health-related quality of life [with the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L)] measures were recorded at baseline and at follow-up visits 4 and 8 weeks after initiation of treatment. Data were analyzed using ANOVA and mixed linear models. Results: 565 patients completed the study and comprised the analyzed dataset. Results indicated that severity of illness significantly decreased over the 8 weeks of the study and already at 4 weeks in both patient groups. Overall quality of life and all of its subindicators also significantly improved in both patient groups and so did subjective experience of pain. Satisfaction with current treatment also significantly increased during the study period. Frequency of side effects was low. In both GAD and MDD groups, two patients dropped out of the study due to adverse effects, leading to treatment termination in four cases (0.7%). Conclusions: This 8-week, multicenter, flexible-dosing, single-arm, open-label, observational real-life study in MDD and GAD patients switched to duloxetine after inadequate response or low tolerability to other ADs showed a significant positive effect on all outcome measures, including a significant decrease in illness severity as well as significant overall symptomatic improvement, with good tolerability.

The complex presentation of carcinomatous meningitis / A meningitis carcinomatosa komplex megjelenése.

Összefoglaló. Az emlotumor miatt kezelt, majd gondozott beteget - több tünetmentes év után - fejfájás, szédülés, ataxia, megváltozott, furcsa viselkedés, emlékezetzavar és dezorientáció miatt neurológiai, majd belgyógyászati osztályokon vizsgálták. Az alapos kivizsgálás ellenére a tüneteit magyarázó organikus eltérést nem igazoltak, ugyanakkor már a kezdetektol felmerült a szomatizációs tünetképzés lehetosége, ezért pszichiátriai osztályos felvételére került sor. Az elvégzett vizsgálatok, illetve a klinikai kép regresszív állapotot valószínusítettek. Terápiás próbálkozásaink ellenére a páciens állapota romlott, végül a megismételt neurológiai vizsgálatok meningitis carcinomatosát igazoltak. Az esettel szemléltetni kívánjuk, hogy a beteg premorbid muködési nívója, személyiségstruktúrája hogyan képes befolyásolni az ellátószemélyzetet, milyen külso és belso konfliktusokat válthat ki. A diagnózishoz vezeto folyamat bemutatásával fel kívánjuk hívni a figyelmet az interdiszciplináris együttmuködés fontosságára. Orv Hetil. 2021; 162(43): 1744-1748. Summary. Our patient with known breast cancer in her past medical history was hospitalized - after several asymptomatic years - for headache, dizziness, ataxia, changed behaviour and disorientation. Thorough internal and neurologic investigations did not find any disease underlying her symptoms, therefore the possibility of somatization disorder was raised. Despite lege artis therapeutic interventions carried out on the psychiatry ward, the patient's condition deteriorated and repeated neurological examinations eventually revealed carcinomatous meningitis. With this case, we would like to illustrate how the patient's premorbid function level and personality features might influence the attitude and opinion of the health care personnel, and what kind of external and internal conflicts might be triggered. By presenting the complexity of the diagnostic work-up, we would like to emphasize the importance of interdisciplinary cooperation in the interest of our patients. Orv Hetil. 2021; 162(43): 1744-1748.

Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping.

The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.

Abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia.

This study was designed to investigate the relationship between abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia. Visual contrast sensitivity for counterphase-modulated low spatial frequency gratings was measured in 32 non-deficit and 12 deficit schizophrenia patients and 20 healthy controls subjects. Abnormal neurological signs were evaluated with the Neurological Evaluation Scale (NES). Compared with the controls, patients with schizophrenia displayed impaired visual contrast sensitivity, which was associated with sensory integration deficits, as measured with the NES. The deficit syndrome was predicted by negative symptoms and sensory integration deficits. These results suggest that early-stage perceptual dysfunctions, which may reflect the abnormality of precortical magnocellular visual pathways, are related to a specific group of abnormal neurological signs.

Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia.

Thirteen male patients with schizophrenia and thirteen male normal control subjects were compared by magnetic resonance imaging (MRI) on volumes of the straight gyrus (SG), anterior cingulate gyrus, middle frontal gyrus, hippocampus, third ventricle, cavum septi pellucidi, total brain volume and intracranial volume. In addition, neuropsychological tasks were used to measure working memory and executive functions. Healthy volunteers and schizophrenic patients showed no significant differences in mean values for volumes of regions of interests. In the case of the SG, we found a significant difference in laterality: the tendency toward left dominance in healthy volunteers changed to significant right dominance in patients. The schizophrenic patients showed lower performance in working memory tasks, and strongly significant group differences were observed in measures of neurological signs assessed by the Neurological Evaluation Scale (NES). Negative symptoms correlated with the level of spatial working memory and executive functions. Negative symptoms also correlated with the volume of the right hippocampus, while the rate of anhedonia negatively correlated with the relative volume of the left SG.

Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers.

Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL) express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3) was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2) and the inwardly rectifying potassium channel (Kir2.3) were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR) using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

Habit learning and the genetics of the dopamine D3 receptor: evidence from patients with schizophrenia and healthy controls.

In this study, the authors investigated the relationship between the Ser9Gly (SG) polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in healthy controls and patients with schizophrenia. Participants were given the weather prediction task, during which probabilistic cue-response associations were learned for tarot cards and weather outcomes (rain or sunshine). In both healthy controls and patients with schizophrenia, participants with Ser9Ser (SS) genotype did not learn during the early phase of the task (1-50 trials), whereas participants with SG genotype did so. During the late phase of the task (51-100 trials), both participants with SS and SG genotype exhibited significant learning. Learning rate was normal in patients with schizophrenia. These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia.

Decrease of the inflammatory response and induction of the Akt/protein kinase B pathway by poly-(ADP-ribose) polymerase 1 inhibitor in endotoxin-induced septic shock.

The lack of efficacy of anti-inflammatory drugs, anti-coagulants, anti-oxidants, etc. in critically ill patients has shifted interest towards developing alternative treatments. Since inhibitors of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) were found to be beneficial in many pathophysiological conditions associated with oxidative stress and PARP-1 knock-out mice proved to be resistant to bacterial lipopolysaccharide (LPS)-induced septic shock, PARP inhibitors are candidates for such a role. In this study, the mechanism of the protective effect of a potent PARP-1 inhibitor, PJ34 was studied in LPS-induced (20mg/kg, i.p.) septic shock in mice. We demonstrated a significant inflammatory response by magnetic resonance imaging in the dorsal subcutaneous region, in the abdominal regions around the kidneys and in the inter-intestinal cavities. We have found necrotic and apoptotic histological changes as well as obstructed blood vessels in the liver and small intestine. Additionally, we have detected elevated tumor necrosis factor-alpha levels in the serum and nuclear factor kappa B activation in liver of LPS-treated mice. Pre-treating the animals with PJ34 (10mg/kg, i.p.), before the LPS challenge, besides rescuing the animals from LPS-induced death, attenuated all these changes presumably by activating the phosphatidylinositol 3-kinase-Akt/protein kinase B cytoprotective pathway.

The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia.

We investigated a novel polymorphism of single nucleotide substitution (C270T) of the brain-derived neurotrophic factor (BDNF) gene in schizophrenia patients (n=101) and in controls (n=68). The frequency of the C/T genotype and the T allele were significantly higher in the schizophrenia patients (25.7% and 13.9%, respectively) compared with the controls (5.9% and 2.9%). There were no significant differences in Positive and Negative Symptom Scale (PANSS) items and Global Assessment of Functioning (GAF) scores between the patients with C/C and C/T genotypes. Further studies are warranted to elucidate the significance of this finding in the pathophysiology of schizophrenia.

Development and characterisation of a monoclonal antibody family against aquaporin 1 (AQP1) and aquaporin 4 (AQP4).

Recent studies have discovered the existence of water-channel molecules, the so called aquaporins (AQP) presumably involved in active, ATP dependent water transport between the intracellular and extracellular compartments. Both genetic and protein sequences and structures of the AQPs are known and crystallographic analyses of some members of the AQP family have been performed. Specific antibodies are required to examine their histological locations and analyse their roles in physiological and pathological pathways of water transportation and osmotic regulation. Until recently some polyclonal antibodies have been developed against certain members of the AQP family. However, to date highly specific monoclonal antibodies against aquaporins do not exist. We have developed a monoclonal antibody family against the aquaporin 1 (AQP1) and aquaporin 4 (AQP4) molecules. Well-conserved epitop sequences of AQP1 and AQP4 proteins were selected by computer analysis and their synthetic peptide fragments were used as the antigens of immunisation and the following screening. Antibodies were characterised by immunoserological methods (ELISA, dot-blot and immunoblot), flow cytometry and immunohistochemistry of formaldehyde-fixed and paraffin-embedded tissue samples. RT-PCR tests controlled the specificity of the immune reactions. Our monoclonal antibodies recognised AQP1 and AQP4 in all the techniques mentioned above and apparently they are useful both in various quantitative and qualitative measurements of the expressions of AQP1 and AQP4 in several species (human, rat, mouse, invertebrates, even plants). According to preliminary immunohistochemical studies our monoclonal anti-AQP1 and anti-AQP4 antibodies are appropriate tools of patho-morphological examinations on routine formol-paraffin tissue samples.