[Dimensions of mentalization in psychotic disorders]. / A mentalizáció dimenziói pszichotikus zavarokban.

The clinical assessment of mentalization became one of the most important issues in clinical psychology and psychiatry. Despite extensive research efforts, the exact definition, classification, and evaluation of mentalization is unresolved, especially in psychotic disorders. The primary purpose of the present study was to investigate the factor structure of the Mentalization Questionnaire. In addition, we investigated the relationship between the dimensions of mentalization and the positive, negative, and general symptoms of psychotic disorders, as well as potential associations with antipsychotic medications. We recruited two independent samples: the first consisted of 94 individuals (schizophrenia, n=63; schizoaffective disorder, n=21; psychotic bipolar disorder, n=10), and the second included 75 patients (schizophrenia, n=60; schizoaffective disorder, n=10; psychotic bipolar disorder, n=5). Exploratory and confirmatory factor analyses revealed four dimensions in both samples: self-reflection, emotional awareness, psychic equivalence, and affective regulation. The two samples did not differ in Mentalization Questionnaire scores. The severity of negative symptoms significantly correlated with weak self-reflection. The dose of first- and second-generation antipsychotics was not associated with mentalization. In summary, the questionnaire is suitable for the measurement of mentalization in psychotic disorders. Mentalization is not a unitary phenomenon: its four psychometric components were differentially associated with clinical symptoms, but not with antipsychotic medications.

[Analysis of antipsychotic prescription data and attendance of patients with schizophrenia in the Hungarian health system]. / Antipszichotikum gyógyszerkiváltási adatok és szkizofrén betegek pszichiátria ellátórendszerben való megjelenésének elemzése.

Regular care and sustained pharmacotherapy are inevitable for people who suffer from schizophrenia in order to attain an acceptable level of quality of life. The National Health Care Service Center (Állami Egészségügyi Ellátó Központ) has a health care utilization database in which individuals can be identified with a specific number, but anonymously (pseudo-TAJ), and their patient pathways can be retraced. We analyzed the health service utilization of patients with schizophrenia in the inpatient and outpatient care and the patterns of prescription and drug dispensing. The results show that in a given year, 30-35% of patients with schizophrenia do not reach the provision system and do not get adequate ("lege artis") therapy. Data concerning the prescription of antipsychotics show that psychiatrists working in Hungary prefer modern medicinal therapies in accordance with the domestic and international pharmacotherapeutic guidelines. These findings suggest that proper clinical care is provided to those patients with schizophrenia and with psychosis in general, who remain in the care system.

[Chemobrain]. / Chemobrain.

Over the past ten years, in oncology there is an increased interest in understanding the cognitive dysfunction caused by chemotherapy also known as chemobrain or chemofog. As a result of oncological therapies the number of survivors of malignant diseases has increased considerably, but the side effects also appear to be more prevalent and severe including persistent cognitive symptoms. Symptoms of chemobrain include memory impairment, loss of concentration, speech and psychomotor deceleration, attention and learning coordination problems, and disturbance of executive functions. The symptoms may be transient but are often long-lasting, the latter negatively affecting functionality and quality of life. Structural and functional imaging studies (MRI, fMRI, PET) and neuropsychological tests are not consistent in the diagnosis of chemobrain. Several factors are suspected leading to the appearance of symptoms, but the specific patomechanism is not yet known. Nutrition status, age, anemia, inflammatory cytokines, stress, and depression can all affect the quality of life and may be related to cognitive symptoms. Currently, there is no treatment strategy for preventing or alleviating cognitive impairement related to chemobrain, and several pharmacotherapies are under investigation. Results imply that understanding the patomechanism of chemobrain can also yield a deeper understanding of cognitive dysfunction associated with depression.

[Investigation of CNTF, COMT, DDR1, DISC1, DRD2, DRD3, and DTNBP1 candidate genes in schizophrenia: Results from the Hungarian SCHIZOBANK Consortium]. / CNTF, COMT, DDR1, DISC1, DRD2, DRD3 és DTNBP1 kandidáns gének vizsgálata szkizofréniában: eredmények a Magyar SCHIZOBANK Konzorcium vizsgálatából.

Schizophrenia is a chronic, debilitating psychiatric disorder characterized by heterogeneous clinical symptoms. Although the pathogenesis of this disorder is poorly understood, several lines of evidence support the role of both common and rare genetic variants in the etiology of schizophrenia. Common variants, single nucleotide polymorphisms can be investigated by candidate gene association studies or genome-wide association studies, while rare variants, single nucleotide variants are assessable by means of candidate gene resequencing or whole-exome and genome sequencing using next generation sequencing. In this study we investigated polymorphisms of 7 candidate genes in a Hungarian schizophrenia cohort. Candidate genes were chosen on the basis of previous results and biological plausibility. 390 patients were recruited in 5 centers in the framework of the Hungarian SCHIZOBANK Consortium, the schizophrenia sample was contrasted to 1069 healthy control individuals. In this sample SNPs of DDR1 and DRD2 genes demonstrated significant association with schizophrenia. The role of DDR1 and DRD2 genes in the etiology of schizophrenia warrant further investigation, based on their genomic localization and biological functions.

Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature.

OBJECTIVE: We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. CASE REPORT: M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. CONCLUSION: To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings.

[Combination of second generation antipsychotics -- case report]. / Második generációs antipszichotikumok kombinációja -- esetismertetés.

Treatment guidelines suggest antipsychotic monotherapy in the treatment of psychosis. 20-40% of patients take combination therapy in clinical practice due to inadequate treatment response to monotherapy. First-generation antipsychotic monotherapy was ineffective in case of our patient who had severe psychotic symptoms. Switching to a second generation antipsychotic had partial therapeutic effect, the severe psychotic condition was persistent. For this reason the therapy was changed to olanzapine-clozapine combination. Due to this combination the patient's psychotic symptoms disappeared. He was able to maintain the relationship with psychiatrist. During this therapy we observed good compliance, no more drug abuse and no relapse.

Investigation of circulating endothelial progenitor cells and angiogenic and inflammatory cytokines during recovery from an episode of major depression.

BACKGROUND: Epidemiological studies strongly suggest a bidirectional positive relationship between mood and cardiovascular disorders (CVD). Reduced numbers of circulating endothelial progenitor cells (cEPCs) are associated with elevated risks of CVD. Previously we demonstrated that patients with a current episode of major depression (MDE) have a decreased number of cEPCs. The role of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) has been demonstrated in the etiopathogenesis of depression. In addition these cytokines are also involved in regulation of the vascular system. This suggests that VEGF and/or TNF may also mediate the elevated risk of CVD associated with mood disorders. METHODS: In the current investigation, which has a self-controlled study design, we examined changes in VEGF and TNF levels and--for the first time--changes in cEPC number during recovery from MDE. RESULTS: Twenty-four patients with MDE were enrolled. The severity of their depressive symptoms improved significantly during the one-month treatment period (~50% decrease in MADRS score; P≤0.001). We did not find significant differences between baseline and end-point levels of VEGF, TNF and the number of cEPCs. CONCLUSION: Our negative result for alteration in the number of cEPCs in the course of recovery from MDE raises several questions. Before discarding the number of cEPCs as a possible marker of depression--and/or elevated CV risk associated with it--our results would require confirmation in larger samples. Our results for TNF and VEGF do not contradict the findings of prior studies, since these were controversial.

[Clinical characteristics of cannabis-induced schizophrenia spectrum disorder]. / Kannabiszhasználat mellett kialakuló szkizofréniaspektrum-zavar klinikai jellegzetességeinek vizsgálata.

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia.

Psychopharmacological comparison of schizophrenia spectrum disorder with and without cannabis dependency.

BACKGROUND: Although incidence of schizophrenia is higher among cannabis users and marijuana is the most common abused drug by adolescents, etiological linkage between schizophrenia and cannabis use is still not clarified. Clinical experiences suggest that regular cannabis user can show similar psychotic episode to schizophrenic disorders but it is still unclear if chronic cannabis use with schizophreniform disorder is a distinct entity requiring special therapy or it can be treated as classical schizophrenia. There are no data available on the comparison of pharmacotherapy between schizophreniform patients with and without cannabis use. METHODS: Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Comparison of anamnesis, family history, social-demographic condition, positive and negative symptoms, acute and long-term therapies recorded by clinical interviews was performed with chi square tests, logistic binary regression and t-tests using SPSS 13.0 for Windows software. RESULTS: Men were over-represented in cannabis dependent group while mean age was lower among them compared to Cnbs0 subgroup. Prevalence of suicidal attempt was increased in men without cannabis use (OR = 5.25, p = 0.016). Patients without cannabis use spent more time in hospital (p = 0.026) and smoking was more frequent among them (OR = 1.36, p = 0.047). The chance to get olanzapine for acute therapy and aripiprazol for long term therapy was more than two fold in Cnbs1 subgroup (OR = 2.66, OR = 3.67, respectively). However, aripiprazol was used for acute therapy with significantly lower risk in Cnbs1 subgroup (OR = 0.47, p = 0.023). Olanzapine was administered for long term therapy in a higher dose to Cnbs0 patients (p = 0.040). Also higher dose of risperidon LAI was used in women without cannabis dependency compared to women of Cnbs1 subgroup (p=0.020). Positive and negative symptoms and family history did not differ significantly between the two subgroups. CONCLUSION: Although symptom profile was similar, hospitalization time, suicidal anamnesis, smoking habit and also dosage, intensity and lasting of therapy were different between the two subgroups. Further prospective studies are required for the investigation of the clinical and molecular background of this discrepancy in order to determine a relevant protocol of prevention and treatment of the chronic cannabis use related psychotic disorder.

[SCHIZOBANK - The Hungarian national schizophrenia biobank and its role in schizophrenia research and in personalized medicine]. / Magyar szkizofrénia-biobank a szkizofréniakutatás és a személyre szabott orvoslás szolgálatában.

Delineating the pathogenesis of multifactorial diseases is a major challenge of the postgenomial era. Genetic factors are known to play an important role in the pathogenesis of certain psychiatric disorders as well as in the development of adverse reactions to psychoactive drugs. Containing large numbers of samples and linking them clinical data, biobanks are gaining importance in the studies of chronic multifactorial diseases. Several biobanks are under establishment in Hungary. The first initiative to collect samples in neurological and psychiatric disorders was the NEPSYBANK coordinated by the Hungarian Society of Clinical Neurogenetics. The national biobank network is currently established by the NEKIFUT project of the National Office of Research and Technology. In this article we describe the structure, logistics and informatical background of the national schizophrenia biobank (SCHIZOBANK). The initiative of the SCHIZOBANK originates from a consortium in which academy and health industry partners are collecting biological materials and data in five major psychiatric center under the coordination of the Medical and Health Science Center of the University of Debrecen. We review other international schizophrenia biobanks as well. Major strength of the SCHIZOBANK is the collection of very detailed phenotypic data and of RNA and plasma both in psychotic and non-psychotic state of the patient which permits longitudinal follow-up and the study of both static and dynamically changing transcriptomic, proteomic and metabolomic markers. The collection of the SCHIZOBANK is available not only to consortial partners but to other national and international research groups as well.

[Akathisia in the course of olanzapine treatment]. / Olanzapin kezelés mellett jelentkezö akathisia.

Olanzapine is a safely and comprehensively applicable atypical antipsychotic drug, for the treatment of schizophrenia, and of the mild to sever maniac episode. In our case study we describe the appearance of akathisia next to olanzapine therapy in the case of a 65 years old woman, and an overview of the literature have reference to adverse events of olanzapine.

[Pharmacovigilance as new direction of research]. / Farmakovigilancia mint új kutatási terület.

Pharmacovigilance: permanent collection and assessment of the safety data of the drug, in the interest of precise knowledge of the safety profile of the pharmacon; permanent collection of unexpected adverse drug reactions, effects on special patient populations, drug interactions, adverse drug reactions of long-term treatment, adverse drug reactions of long latency. Our study was performed under the tutelage of the Drug Safety Programme in Psychiatry (AMSP), 2004. We review the side effects occuring in the different organ systems; side effects during the use of antidepressive and antipsychotic therapy. We review how the danger of polypharmacy can be avoided by reducing the dose of the current drug; by using therapeutic drug; or just by monitoring therapeutic and adverse effects.

Clozapine maintenance therapy in schizophrenia.

Long-term pharmacotherapy with antipsychotic agents is an important aspect of the management of schizophrenia. In patients responsive to the chosen treatment, maintenance therapy is usually conducted by halving the drug dose that has proven effective during the acute phase. This strategy is suitable for maintaining remission; moreover, it can improve the patients' quality of life. Records from over 1000 patients treated with clozapine during the past 22 years were examined; 782 of these patients were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria (with the modification in early years). From this group, 181 patients were treated with clozapine for at least a year. The mean duration of long-term maintenance treatment with clozapine was 12.2+/-4.25 years (range: from 14.5 months to 18 years). Clozapine was administered in a daily dose of 50-200 mg (mean: 71.5+/-14.12 mg). In 76 schizophrenics, treatment was initiated with clozapine, whereas 105 patients were switched over from other treatments after their failure. The control group comprised 152 patients on long-term maintenance therapy with haloperidol. Clozapine administered for long-term maintenance therapy was effective both in paranoid and in catatonic schizophrenia. It also accomplished good results in patients with disorganized or residual schizophrenia, as well as in individuals with schizoaffective psychosis. Relapse rate was similar to that observed in the haloperidol group; however, patient compliance, side-effect profile, and therapeutic efficacy were all superior in the clozapine group. Long-term maintenance therapy with clozapine is successful. Compliance is good; schizophrenic patients are willing to take this atypical antipsychotic for years on end. Clozapine treatment is associated with a low relapse rate and a favorable safety profile.

Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia.

Neuroimaging studies have implicated the prefronto-striatal loop as a substrate for the cognitive deficits in schizophrenia (SCHZ). Postmortem morphometric studies reveal that layers III and V of the dorsolateral prefrontal cortex (dlPFC), which gave rise to glutamatergic projections to neostriatum, demonstrate the most structural pathology in this region of the SCHZ. These neuronal alterations in SCHZ are not accompanied by marked glial changes as revealed by Nissl staining. We examined the glial-type specific pathology in SCHZ by analyzing the glial fibrillary acidic protein- (GFAP) immunoreactive astroglia in contrast to the Nissl-stained general pool of glial cells in dlPFC (area 9) from 9 subjects with SCHZ and 15 psychiatrically normal control subjects. In layer V of the dlPFC in SCHZ, there was a significant 32% reduction in the GFAP-area fraction, 81% increase in the density of the GFAP-positive cell bodies and a 14% decrease in the width of the cortical layer V, as compared to the control subjects. None of these parameters were affected in layers III and IV in the SCHZ. Therefore, only subtle, type- and layer-specific glial pathology is present in the dlPFC in SCHZ. Astroglial pathology in dlPFC may reflect disturbances of the neuron-glia interactions in layer V and may be related to the dysfunctional prefronto-striatal circuits, dopaminergic alterations and cognitive pathology in SCHZ.

Agranulocytosis during clozapine therapy.

Granulocytopenia and agranulocytosis are considered among the most dangerous adverse effects of clozapine. During the last 15-year period, this atypical antipsychotic agent has been administered to 750 patients managed at the Emergency Psychiatry Services and Clinical Pharmacology Unit of the National Institute of Psychiatry and Neurology (NIPandN; Budapest, Hungary). Granulocytopenia was ascertained in seven, whereas agranulocytosis was diagnosed in two patients of this population. The latter two comprised a 42-year-old female with schizoaffective psychosis and a 35-year-old male with paranoid schizophrenia. The female patient received clozapine in a daily dose of 400 mg, which induced agranulocytosis after 2 months. The male patient was treated with 225-mg/day clozapine and the time to the diagnosis of agranulocytosis was 6 weeks. These adverse reactions were recognized early and the appropriate treatment of agranulocytosis resulted in complete recovery in both cases.