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Clinical Neuroscience

SEPTEMBER 30, 2020

TLR4 (Toll-like receptor-4) expression and frontal-cingulate volumes in schizophrenia

LI Hua, KÉRI Szabolcs

Evidence suggests that pathogen-associated pattern recognition receptors (Toll-like receptors, TLRs) are implicated in the pathophysiology of schizophrenia. TLRs are important in both peripheral immune responses and neuronal plasticity. However, the relationship between peripheral TLR expression and regional brain volumes is unknown in schizophrenia. We therefore assessed 30 drug-naïve, first-episode patients with schizophrenia. TLR4+/TLR1+ monocytes were measured using flow-cytometry. High resolution magnetic resonance images (T1 MRI) were obtained and analyzed with FreeSurfer. Results revealed significant negative correlations between the percentage of TLR4+ monocytes, mean fluorescent intensities, and brain volumes in frontal and anterior cingulate regions. The measures of TLR1+ monocytes did not show significant relationships with regional brain volumes. These results raise the possibility that abnormal TLR-activation is associated with decreased brain volumes in schizophrenia.

Clinical Neuroscience

JANUARY 30, 2016

[Event-related potentials and clinical symptoms in schizophrenia]


[The investigation of schizophrenia’s aetiology and pathomechanism is of high importance in neurosciences. In the recent decades, analyzing event-related potentials have proven to be useful to reveal the neuropsychological dysfunctions in schizophrenia. Even the very early stages of auditory stimulus processing are impaired in this disorder; this might contribute to the experience of auditory hallucinations. The present review summarizes the recent literature on the relationship between auditory hallucinations and event-related potentials. Due to the dysfunction of early auditory sensory processing, patients with schizophrenia are not able to locate the source of stimuli and to allocate their attention appropriately. These deficits might lead to auditory hallucinations and problems with daily functioning. Studies involving high risk groups may provide tools for screening and early interventions; thus improving the prognosis of schizophrenia. ]

Lege Artis Medicinae

JANUARY 20, 2020

[Clozapine - the last resort antipsychotic for treatment resistant schizophrenia ]


[More than 60 years old is the first antipschychotic drug that is operating atypically as well. With its multifarious history it gained the golden standard title of all therapy resistent schisophrenic cases for the last three decades. In this article we place clozapine on the map of psychopharmacology and review its history’s most important chapters. In the third part we discuss some of the most relevant effects and side effects of clozapine in the light of latest research and practical considerations touching the problem of the optimal start timing. ]

Clinical Neuroscience

NOVEMBER 30, 2019

[Tracing trace elements in mental functions]

JANKA Zoltán

[Trace elements are found in the living organism in small (trace) amounts and are mainly essential for living functions. Essential trace elements are in humans the chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), and questionably the boron (B) and vanadium (V). According to the biopsychosocial concept, mental functions have biological underpinnings, therefore the impairment of certain neurochemical processes due to shortage of trace elements may have mental consequences. Scientific investigations indicate the putative role of trace element deficiency in psychiatric disorders such in depression (Zn, Cr, Se, Fe, Co, I), premenstrual dysphoria (Cr), schizophrenia (Zn, Se), cognitive deterioration/de­mentia (B, Zn, Fe, Mn, Co, V), mental retardation (I, Mo, Cu), binge-eating (Cr), autism (Zn, Mn, Cu, Co) and attention deficit hyperactivity disorder (Fe). At the same time, the excess quantity (chronic exposure, genetic error) of certain trace elements (Cu, Mn, Co, Cr, Fe, V) can also lead to mental disturbances (depression, anxiety, psychosis, cognitive dysfunction, insomnia). Lithium (Li), being efficacious in the treatment of bipolar mood disorder, is not declared officially as a trace element. Due to nutrition (drinking water, food) the serum Li level is about a thousand times less than that used in therapy. However, Li level in the red cells is lower as the membrane sodium-Li countertransport results in a Li efflux. Nevertheless, the possibility that Li is a trace element has emerged as studies indicate its potential efficacy in such a low concentration, since certain geographic regions show an inverse correlation between the Li level of drinking water and the suicide rate in that area. ]

Lege Artis Medicinae

OCTOBER 20, 2019

[Population-level QALY gain estimates with the use of cariprazine for patients with negative symptoms of schizophrenia in Hungary]

BENDES Rita, NÉMETH Bertalan, PITTER János György, KÓCZIÁN Kristóf, GÖTZE Árpád, KALÓ Zoltán

[INTRODUCTION - The loss in quality of life caused by mental illnesses has been growing in developed countries. This study aims to quantify the possible gains in quality of life by advantages of cariprazine therapy while treating patients with negative symptoms of schizophrenia in Hungary. Comparator therapy was defined as the currently available second-generation oral antipsychotic drugs. METHODS - In order to estimate the reachable gain in quality of life with cariprazine, an 8-state deterministic Markov cohort model was developed. Data was gathered from relevant scientific literature and public databases. The main assumptions regarding patient pathways have been validated by clinical experts, based on their real-life experience. The number of patients with negative symptoms of schizophrenia was estimated by the same methods as well. Sensitivity analyses were conducted on the input parameters. RESULTS - When compared with currently available second-generation oral antipsychotics, cariprazine generated an estimated increase of 0.05 quality-adjusted life years per patient in 2 years run. The deterministic sensitivity analysis confirmed the robustness of the results. Based on data of the National Health Insurance Fund and the scientific literature, a total gain of 450 quality-adjusted life years is expected at national level over a time horizon of 2 years. Even higher gains of QALY can be expected for longer time horizons. CONCLUSION - Based on conservative estimates significant health gain can be ge­ne­rated, if all patients with negative symp­toms of schizophrenia would receive the adequate cariprazine therapy in Hungary in­stead of the currently used se­cond-ge­ne­ration oral antipsychotic drugs. ]

Lege Artis Medicinae

SEPTEMBER 10, 2019

[Path of life in the society with a diagnosis of a psychiatric disease ]


[INTRODUCTION - The aim of our study is to show how people can live with a diagnosis of a psychiatric disease, a schizophrenia diagnosis in Hungary. METHODOLOGY - We made 25 narrative life story interviews with Hungarian people diagnosed with mental illnesses. We examined what the main obstacles and supporting factors may be in the life stories regarding the independent lifestyle and participation in community. RESULTS - According to the interviewees the main obstacles are their states or diseases, the stigmas after their diagnoses, the function of the psychiatric care system and the lack of self-reliance following the patient role. They mentioned the family and their own motivations as supporting factors. CONCLUSION - The examination of the institutional functions can reveal what the supporting factors may be which can facilitate the social participation of people diagnosed with mental illnesses on the level of the system. ]

Clinical Neuroscience

MARCH 30, 2018

[Schizotypal traits and verbal creativity]

FEJES Nikolett Éva, RÓZSA Sándor, MUST Anita

[Introduction - The relationship of schizophrenia and its milder, subclinical forms, with creativity has been in the centre of theoretical interest for decades, however, the systematic research of the topic only prevailed more recently. Purpose - Here we aimed to examine the connection between different schizotypal and non-schizotypal personality traits and verbal creativity in a nonclinical sample. We also investigated the correspondence of two schizotypy inventories, the Oxford-Liverpool Inventory of Feelings and Experiences and a special character configuration of the Temperament and Character Inventory associated with schizotypy. Method - 57 healthy adults (14/43 m/f, mean age 21.51±1.43 years) - took part in the experiment. All participants received a detailed information sheet and gave informed consent prior to participation. Participants completed the Oxford-Liverpool Inventory and the Temperament and Character Inventory to measure both schizotypal and non-schizotypal personality traits. Torrance Test of Creative Thinking was used to measure verbal creativity. Associations between reported measures were examined with correlational and regression analyses. Results and conclusion - Out of the specific Temperament and Character configuration associated with schizotypy (low self-directedness, cooperativeness and high self- transcendence), we only found low self-directedness to be correlated significantly with Oxford-Liverpool schizotypy rates (Self-directedness-schizotypy: r=-.730, p<.01). There was no significant connection between schizotypal traits and verbal creativity. In our sample, the Self-directedness and Reward-dependence character and temperament subscales predicted significantly the verbal creativity level (Self-directedness: b=.330, p=.015; Reward - dependence: b=-.260; p=.049). Based on our results, besides schizotypal traits, other personality measures might be considered in relation to verbal creativity, providing further details to the empirical investigation of creativity. We found low self-directedness to be correlated with Oxford-Liverpool schizotypy rates, however, the sample size was not large enough to test the concurrent validity of the two inventories. Future studies might consider to extend the study sample, preferably to both clinical and non-clinical populations.]

Lege Artis Medicinae

JANUARY 20, 2018

[Is the evolvement of schizophrenia preventable?]


[Considering the developmental nature of the majority of mental disorders, these days prevention has increasingly come into the focus of psychiatry. Schizophrenia - one of the disorders that are most frequently associated with psychosis, one of the most serious psychiatric syndromes - is the leading cause of permanent disability of the young adult generation. A prodrome lasting for several years precedes the onset of the first psychotic episode, which offers an opportunity for preventive interventions. Currently, we have two strategies for the predicition of the outburst of psychotic disorders. The Ultrahigh-risk approach can predict the first psychotic episode regardless of diagnosis, while the Basic symptom strategy predicts the development of schizophrenia specifically. However, there is an inverse relationship between the sensitivity and the specificity of different predictive criteria, which raises clinical and ethical dilemmas for the doctors. The methods of repeated assessments of the help-seeking individuals’ clinical states with designation of syndrome stages, and multivariate analyses of emprirically derived markers have proven promising tools for establishing more balance between the sensitivity and specificity of predictive criteria. Interven­tions of the secondary prevention aim to decrease the morbidity of the underlying pathomechanisms, and to help individuals’ coping with alterations of their experiences. We can consider here the psychosocial interventions as evidence based choices, which we can combine with certain food supplements and well-chosen psychopharmacons de­pending on the clinical state. With our in­terventions, we can influence the process of the individual development with vulnerable basis and steer it toward resilience. ]

Lege Artis Medicinae

JANUARY 20, 2018

[Classical methods in modern approach. Training for the recognition of emotions using bibliotherapy-techniques]

SZABÓ József, SIPOS Mária

[BACKGROUND - Nowadays it is an understood fact, that theory of mind has a great psychological significance. Deficits of theory of mind skills are observed in schizophrenia such as depression, dementia, autism and some personality disorders as well. Conceptions of theory of mind and emotion recognition ability have been coming in front at the expanse of the older empathy also in the present-day research in connection with helper connections and their effects. It is probably due to popular approach of cognitive neuroscience exact methods. METHODS - We intended to demonstrate, that the ability of emotion recognition can be developed, or partially restored, even in case of patients suffering from schizophrenia. We compiled an 8-seat training. Our method was a bibliotherapy training, each of chosen novels expressed one of basic emotions (by Ekman). After a common reading we projected validated portraits expressing also those emotions. Participants had to choose reflecting the emotional state of the characters photos. Then they shared stories from their own lives experiencing similar emotions. We measured the effectiveness of our method by the Reading the Mind in the Eyes measured (RMET) test. RESULTS - Comparing data before and after the training in t-test we detected significant difference (p=0.000608 <0.05). Verifying that the observed changes are not only the common effects of the other types of treatment, the same tests were performed on a similar in-patient treated control group. There was no significant difference between the RMET first time and two weeks later values of the control group (p=0.467). The rate of changes in the test and control group (RMET) was compared in a paired-sample t-test, and we also found a significant difference: p=0.000786 <0.005. CONCLUSIONS - The deficit of theory of mind in schizophrenia can be reduced, which indirectly can improve our patients' communication and adaptation skills, or worse, their deterioration can be reduced.]

Clinical Neuroscience

MARCH 30, 2017

[Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia]

PULAY Attila József, KOLLER Júlia, NAGY László, MOLNÁR Mária Judit, RÉTHELYI János

[Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives - The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multilocus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods - Associations of single nucleotide and indel markers were transferred to gene- and geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results - After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xq13 cytobands were found (p_corr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (P_rep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses. ]