Change of Circulating Vascular Endothelial Growth Factor Level and Reduction of Anhedonia Are Associated in Patients With Major Depressive Disorder Treated With Repetitive Transcranial Magnetic Stimulation.

Aim: Vascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressant therapies as it plays a significant role in the neurogenesis. Anhedonia, an endophenotype of major depressive disorder (MDD), is related to the dorsolateral prefrontal cortex, the major focus of brain stimulation in MDD. The aim of our study was to analyze the change of serum VEGF level after rTMS treatment in association with anhedonia. Materials and Methods: A dataset of 17 patients with TRD who were treated with antidepressants and bilateral rTMS for 2 × 5 days was analyzed. Depression was measured by the Montgomery-Asberg Depression Scale (MADRS) and anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS) for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2), and on the 28th day (V3). The level of VEGF was measured by ELISA assay. Results: There was no significant association between MADRS scores and serum VEGF levels at any timepoint. The decrease in the SHAPS score was significantly associated with the increase in VEGF level between V1 and V2 (p = 0.001). The VEGF levels were significantly higher in non-responders than in responders (p = 0.04). The baseline VEGF level has been proven as a significant predictor of treatment response (p = 0.045). Conclusion: Our results suggest that serum VEGF can be sensitive to the changes of anhedonia during rTMS treatment. Considering that the most widely used depression scales are not applicable for the assessment of anhedonia, measurement of anhedonia in rTMS treatment studies of patients with TRD can be suggested as more appropriate data on distinct pathogenic pathways and specific biomarkers of the disorder.

Peripheral endocannabinoid serum level in association with repetitive transcranial magnetic stimulation (rTMS) treatment in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well tolerable biological intervention in major depressive disorder (MDD) contributing to rapid symptom improvement. Molecular mechanisms underpinning the therapeutic effects of rTMS have still not been clarified. Recently published animal data implicated relevant associations with changes in endocannabinoid (eCB) brain levels during rTMS treatment, human studies, however, have not been published. In our study we assessed the detailed phenotypic spectrum of MDD and serum 2-arachidnoylglycerol (2-AG) and anandamide (AEA) levels in 18 patients with treatment-resistant depression before, immediately following, and two weeks after completion of a 10-day rTMS treatment. We found significant associations between serum 2-AG level changes from pretreatment to 2 weeks after treatment and symptom reduction. The greater the increase of 2-AG levels, the greater the improvement of depressive (p = 0.031), anxious (p = 0.007) and anhedonia symptoms (p = 0.047). Here we report for the first time a significant association of human circulating eCB and antidepressant effect of rTMS. Our data may indicate that direct stimulation of targeted brain areas can rapidly alleviate depressive complaints via activation of the eCB system.

[The use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder: theoretical and practical considerations].

In the last 2 decades, a growing body of evidence documented the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric diseases, especially of major depressive disorder (a.k.a. unipolar depression). In our paper, we discuss briefly the historical aspects of TMS, its position among neurostimulatory methods and its mechanism of action. Then we review in details the practical aspects of the application of rTMS (e.g. stimulation parameters, contraindicatitions, side-effects) as well as the evidences of its efficacy in the treatment of depression. We also outline the possibilities of the use of rTMS in other psychiatric disorders than MDD. In our opinion, more than 10 years after receiving the FDA clearence, rTMS should be added to the Hungarian treatment guideline of MDD. Furthermore, the elaboration of the details of the insurance coverage of the rTMS treatment by the Hungarian National Health Insurance Fund would also be required.

[Investigation of the acute effect of bilateral repetitive transcranial magnetic stimulation (rTMS) in therapy resistant major depression patients]. / Bilaterális repetitív transzkraniális mágneses stimuláció (rTMS) akut hatásának vizsgálata terápia rezisztens major depresszióban szenvedok körében.

INTRODUCTION: There is a 20-year history of rTMS treatment, however, is not available in Hungary in routine clinical practice for therapy resistant depression (TRD). In this study we analysed the change of symptom profile of a Hungarian cohort with TRD using bilateral rTMS treatment. METHODS: A cohort of 22 patients suffering from TRD was enrolled in the study. For assessment of the phenotypic profile the Beck Depression Inventory (BDI), The Beck Anxiety Inventory (BAI), The Montgomery-Asberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Insomnia Severity Index (ISI), and the Trail Making Test were applied. Differences of mean scores of scales were compared between the day 1 (before treatment) and the day 14 (after conclusion of treatment). Furthermore, we performed phenotypic comparisons between the gender subgroups. RESULTS: In the total sample significant reduction of symptom scores was found on the depression (pMADRS=0,022; pBDI=0,001) and the anxiety scales (pBAI=0,020) and in case of the TMT-A test (pTMT-A=0,019) at the end of the treatment. The mean scores of the SHAPS, the ISI and the TMT-B did not change up to the day 14. In the sex-specific analysis we found that in men only sleep disorder was improved (p=0,015), while in women both depression scores and TMT-A score decreased significantly (MADRSp=0,015; BDIp=0,005; TMT-Ap=0,036). There were no adverse events during the rTMS treatment. CONCLUSION: 2x5 sessions of bilateral rTMS treatment is an effective, safety applicable intervention in patients with TRD. Our results suggest that significant improvement of depressive, anxious and attention symptoms can be observed already after 10th session. Our findings highlighted that different symptoms evolve in women and men due to the acute effect of the rTMS treatment. Further follow-up study is required to evaluate the long-term effect of rTMS concerning the maintenance of symptom reduction and potential change of anhedonia and insomnia.

[Vascular endothelial growth factor (VEGF) as a potential biomarker in major depressive disorder]. / Vaszkuláris endoteliális növekedési faktor (VEGF) mint potenciális biomarker major depresszióval összefüggésben.

BACKGROUND: There is growing evidence that vascular endothelial growth factor (VEGF) plays a crucial role in neurodevelopment and regeneration. Several data support that intact VEGF pathway is indispensable for therapeutic effect of antidepressants, any disruption of VEGF signaling can result treatment resistance. In our study we investigated the peripherial blood VEGF level before and 4-week after antidepressant treatment in patients with major depressive episode and we compared VEGF levels between responders and non-responders. METHODS: We recruited 34 patients diagnosed with major depression disorder rom our department. Depressive symptoms were followed by the Montgomery Asberg Depression Scale. Level of VEGF was measured from peripheral plasma by ELISA technic. For comparisons we performed general linear models and Mann-Whitney U tests. RESULTS: Baseline VEGF level was significantly higher in the non-responder subgroup compared to responders (p=0.017). In regression analyses the baseline and end-point VEGF levels were correlated with end-point MADRS (p=0.03; p=0.02, respectively). In our sample the higher baseline VEGF level was correlated with 2.75 times greater chance for treatment resistance in non-responders compared to responders. CONCLUSION: Our results confirm the significant role of VEGF signaling in the pathomechanism of major depression disorder. These data suggest that high baseline VEGF level can be a predictor for lack of therapy response, thus VEGF can be regarded as a potential biomarker for treatment resistance in major depression disorder.

Maternal bonding styles in smokers and non-smokers: a comparative study.

BACKGROUND: Parental bonding has been implicated in smoking behavior, and the quality of maternal bonding (MB) has been associated with poor mental health and substance use. However, little is known about the association of MB and the smoking of the offspring. METHODS: In our study, 129 smokers and 610 non-smoker medical students completed the parental bonding instrument, which measures MB along two dimensions: care and overprotection. Four categories can be created by high and low scores on care and overprotection: optimal parenting (OP; high care/low overprotection); affectionless control (ALC; low care/high overprotection); affectionate constraint (AC; high care/high overprotection), and neglectful parenting (NP; low care/low overprotection). Nicotine dependence was assessed by the Fagerstrom Nicotine Dependence Test, exhaled CO level, and daily cigarette consumption (CPD). RESULTS: Higher CPD was significantly associated with lower overprotection (p = 0.016) and higher care (p = 0.023) scores. The odds for being a smoker were significantly higher in the neglectful maternal bonding style compared to the other rearing styles (p = 0.022). Besides, smokers showed significantly higher care and lower overprotection scores with the Mann-Whitney U-test than non-smokers, although these associations did not remain significant in multiple regression models. CONCLUSION: Our results indicate that focusing on early life relationship between patient and mother can be important in psychotherapeutic interventions for smoking. Registration trials retrospectively registered.

[Personalized medicine in psychiatry: nightmare of the industry?] / 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.

[Emergency psychopharmacotherapy in Hungary -- preliminary data]. / Sürgosségi pszichofarmakoterápia Magyarországon -- elozetes adatok.

OBJECTIVES: Although the number of patients admitted for psychiatric emergency care is increasing according to data from various countries, there are no large-scale studies assessing clinical emergency practice and in several countries no national guidelines have been published concerning emergency care in psychiatry. The aim of our study was to assess practice related to emergency care of agitated-psychotic patients in Hungary. METHODS: Anonymous survey questionnaire with questions related to care of an agitated patient showing psychotic symptoms was dispatched to 210 institutions providing psychiatric care in Hungary in 2013. RESULTS: The overwhelming majority of the 155 participating clinicians would use haloperidol (92.9%) and benzodiazepines (81.3%), 74.8% in a dual combination. 18.7% would apply monotherapy and 5.2% a triple combination of medications. 59.4% would use i.v. and 23.9% i.m. therapy, and 9% would apply the combination of these two. In case of failure of first-line therapy, 76.8% of participants would repeat the previous medication. CONCLUSIONS: The aim of our study was to assess emergency interventions in psychiatry focusing on different psychopharmacological approaches. Our results provide a cross-sectional view on current practice in Hungary, and therefore may contribute to outlining practice-coherent guidelines and also provide the opportunity for a comparison with international trends.

[Successful clozapine treatment of primary polydipsia associated with hyponatraemia in a schizophrenic patient. A case report]. / Szkizofrén beteg primer polidipsziájának és ehhez társuló hiponatrémiának clozapin kezelése. Esettanulmány.

Polydipsia is the intake of more than 3-4 litres of fluids per day. Primary polydipsia (PP) occurs when excessive fluid intake cannot be explained by an identified medical condition. PP has a prevalence varying between 6% and 20% in the population of chronically hospitalized psychiatric patients. Hyponatraemia--sometimes with severe somatic consequences--developing in 25-86% of these patients. We discuss the case of a schizophrenic patient who had polydipsia, polyuria and hyponatremia without any known medical conditions in the etiological background of these symptoms. In accordance with data of literature, clozapine medication was effective in the treatment of this severe condition.