Orvostanhallgatók Magyarországon: átalakuló vagy elnőiesedő hivatás?

Bevezetés: Az orvostanhallgatók pályaszocializációjáról, testi-lelki egészségéről számos hazai és nemzetközi vizsgálat született. Célkitűzés: A medikusok pályaválasztással kapcsolatos motivációinak, testi-lelki egészségének és stresszterhelésének összehasonlítása. Módszer: Orvostanhallgatók (n = 731) körében végzett országos, kvantitatív felmérés. Eredmények: A medikák korábban döntenek az orvosi pálya mellett, nem áll előttük orvosszerepmodell és a pályaválasztási motivációik altruisztikusabbak a medikusokkal összehasonlítva. Az orvostanhallgató nők jobban érintettek a pszichoszomatikus tünetekben és több stressztényezőről számolnak be, mint férfi kollégáik. Nagyobb arányban fordul elő körükben alvászavar, túlterheltebbnek érzik magukat, valamint a kiégés emocionális kimerülés komponense is szignifikánsan nagyobb mértékben jelentkezik körükben. Következtetések: A vizsgálat eredménye felhívja a figyelmet arra, hogy a medikák testi-lelki egészségvédelme kulcsszerepű a későbbi orvosnői morbiditás megelőzésében

Egyénre szabott terápia: a gyógyszeripar rémálma?

Personalized medicine is a hot topic in the literature of the psychiatric field but it seems that regular clinical application of valid tests are awaited. Urgent requirement of objective tools for screening high-risk patients is postulated by prominent authors because long-term set up time, serious side effects or ineffectiveness of psychiatric agents mean a great challenge for clinicians to find optimal therapy on time. Unwanted suffering from inaccurate medicine, progression of the disorder and mistrust or in adherence of the patients are dramatic consequences of the delay of adequate therapy which is linked with irreversible health and mental damages and financial loss. On the other hand, a growing body of data are published on pharmacogenomic studies in association with psychiatric conditions. Although several pharmacogenetic tests are commercially available, accurate use of these tools are absent from clinical protocols. Here we give a short review on the most important pharmacogenomic results and a discussion on possible conflict of interests around pharmacogenetic tests. We conclude that all participants of the health care system could benefit from personalized medicine in psychiatry

The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype.

OBJECTIVES: Neuronal nicotinic acetylcholinergic receptors (nAChR) and especially alpha4beta2 nAChRs are the major targets for cessation medications and also for some promising antidepressant agents. Furthermore, depressive symptoms pose multifacet difficulties during cessation therapy. However, gene encoding for the beta2 subunit of nAChRs has been poorly investigated in association with depression. Since both nicotine dependence (ND) and depressive phenotype are complex disorders, we investigated the effects of a significant early life experience, maternal bonding style (MB) and CHRNB2 gene SNPs on smoking-related depression. METHODS: We recruited two hundred and thirty-two treatment-seeking smokers in our study. Phenotypic variants were evaluated using the Fagerstrom Test for Nicotine Dependence (FTND), the Zung Self-Rating Depression Scale (ZSDS) and the Parental Bonding Instrument (PBI). Besides the total score (TS) of ZSDS, impulsivity (ZSDS-I) and suicidal ideation (ZSDS-S) were distinguished as phenotypic variable. DNAs were extracted from buccal mucosa samples and one SNP in promoter and two SNPs in 3' UTR of CHRNB2 gene were genotyped. GLM and ANOVA tests were performed for genotype associations and interaction analyses. RESULTS: Maternal bonding had a significant impact on depressive phenotypes. Low care, high protection and affectionless control (ALC) were associated with ZSDS-TS and all subphenotypes of ZSDS. One SNP, the rs2072660 in 3' UTR, had a significant effect on the FTND score (p=0.010). Direct association of CHRNB2 variants and depressive phenotypes were not significant. However, in interaction with ALC, rs2072660 was significantly associated with ZSDS-S (p=0.005). MB had no significant effect on smoking-related phenotype. CONCLUSIONS: Our results highlight the important role of 3' UTR in the CHRNB2 gene in the shared molecular background of ND and depressive phenotype. Parental bonding style can be suggested as a significant environmental factor in further GxE studies of depression. The presented significant GxE interaction on smoking-related suicidal subphenotype may help establish further investigations on development of more effective and safer smoking cessation and antidepressant agents

Discrepancy Between Low Levels of mTOR Activity and High Levels of P-S6 in Primary Central Nervous System Lymphoma May Be Explained by PAS Domain-Containing Serine/Threonine-Protein Kinase-Mediated Phosphorylation

The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies. Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1 cell line. mTOR-pathway activity was significantly less frequent in PCNSL compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but not in PCNSL. Among the other kinases potentially responsible for S6 phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL. Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that PASK may contribute to the phosphorylation of S6. Our findings also suggest a potential role of PASK in the pathomechanism of PCNSL and in DLBCL