An expert review of clozapine in Eastern European countries: Use, regulations and pharmacovigilance.

OBJECTIVES: To compare the prevalence, regulations, and pharmacovigilance practices of clozapine use in Eastern European countries (except Russia). METHODS: Questionnaires and data from administrative databases (2016 and 2021), package inserts and national guidelines were collected from 21 co-authors from 21 countries. Reports of clozapine adverse drug reactions (ADRs) sent to the global pharmacovigilance database (VigiBase™) were analyzed from introduction to December 31, 2022. RESULTS: Clozapine prescription among antipsychotics in 2021 varied six-fold across countries, from 2.8 % in the Czech Republic to 15.8 % in Montenegro. The utilization of antipsychotics in both 2016 and 2021 was highest in Croatia, and lowest in Serbia in 2016, and Montenegro in 2021, which had half the defined daily dose (DDD)/1000/day compared to the Croatian data. From 2016 to 2021, the prevalence of antipsychotic use increased in almost all countries; the proportion of clozapine use mainly remained unchanged. Differences were detected in hematological monitoring requirements and clozapine approved indications. Only a few national schizophrenia guidelines mention clozapine-induced myocarditis or individual titration schemes. The VigiBase search indicated major underreporting regarding clozapine and its fatal outcomes. By comparison, the United Kingdom had less than half the population of these Eastern European countries but reported to VigiBase more clozapine ADRs by 89-fold and clozapine fatal outcomes by almost 300-fold. CONCLUSION: Clozapine is under-utilized in Eastern European countries. Introducing individualized clozapine treatment schedules may help to maximize clozapine benefits and safety. Major improvement is needed in reporting clozapine ADRs and fatal outcomes in Eastern European countries.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

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.

Sick leave duration as a potential marker of functionality and disease severity in depression.

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity.Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

[Can we influence the negative drug attitude? Interpretation of the rejection of COVID-19 vaccine in the light of results of a pilot study].

Background and purpose: Vaccination refusal is a serious obstacle to minimizing the spread of COVID-19. Nevertheless, the rejection of vaccine can be considered the result of a negative attitude towards medical treatment, and according to our previously published data, it can be influenced by the underlying affective state. Increased incidence of affective disorders and anxiety could be observed globally during the pandemic, which may have a significant impact on vaccination acceptance. The aim of our pilot study was to determine the association between clinical improvement of affective and neurocognitive symptoms and change of drug attitude and health control beliefs in a sample of psychiatric patients. Methods: A data set of 85 patients with psychiatric disorder has been analysed with the use of Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) with 5 subscales (Negative Aspect of Medication - NA; Positive Aspect of Medication - PA; Doctor health locus of control- Doctor HLOC; Internal HLOC; Psychological Reactance - PR); Hospital Anxiety Depression Scale (HADS-Anx; HADS-Dep) and neurocognitive tests, such as the Stroop test and the Trail Making Tests. All the tests were performed before and after a 14 days treatment. Paired t-tests and generalized linear models were performed to assess the associations between the variables. Results: The baseline scores of NA and HADS-Anx correlated significantly (p=0.001) and after two weeks of treatment NA decreased (p=0.001), while Doctor HLOC and Internal HLOC increased (p=0.001 and p=0.006). The patients performance of the neurocognitive tests improved (all p<0.05). The reduction of HADS-Anx (p=0.002) and HADS-Dep (p=0.006) scores showed significant associations with the decrease of NA. Increase of the PA score was associated with reduction of HADS-Dep (p=0.028). Improvement of neurocognitive functions had no effect on PHBQPT scores. Conclusion: Important conclusions can be drawn regarding the rejection of the COVID-19 vaccine based on the associations found between the intensity of affective and anxiety symptoms and the attitude towards treatment. Our findings suggest that affective symptoms have a negative influence on the attitude towards treatment and that the improvement of these symptoms can facilitate the acceptance of the therapy, regardless of diagnosis. The modest effect of the improvement of neurocognitive functioning on the attitude towards drugs and the significant role of affective-emotional factors suggest that the accep-tance of vaccination probably cannot be facilitated solely with the aid of educational programs. Considering the increasing incidence of affective disorders during the COVID-19 pandemic, the screening of affective and anxiety symptoms and treatment of these disorders could be an important step towards the acceptance of the vaccine. Although psychiatry is not considered as a frontline care unit of the COVID cases, more attention is needed to pay on the availability of mental health services because refuse of vaccine can develop due to affective disorders too.

Practical Approach to Measuring and Predicting Medication Adherence by Outpatient's SelfReport After More than 10 Years of Research in Psychopharmacology.

Schizophrenia, bipolar disorder and major depression are associated with nonadherence registered mean figures of around 50%, highlighting the relevance of having simple adherence tools to incorporate into daily clinical practice. For 10 years we have focused on self-report as an assessment method and have studied thousands of outpatients taking thousands of psychiatric medications in three countries. Measurement of treatment adherence during use of polypharmacy is a really complex task as patients could adhere differently to the various medications prescribed, making it essential to assess adherence to each individual medication. This was not possible until the introduction of the Sidorkiewicz Adherence Tool that allows one to separate adherence to each medication, whether poor or not. Health psychologists have developed the Health Belief Model which has not received enough attention by psychiatrists. Based on this model, we have focused on personality styles and specific beliefs concerning specific medications as possible predictors of poor adherence. We developed the Patient Health Beliefs Questionnaire on Psychiatric Treatment which provides 5 self-reported personality dimensions: negative aspects of medication (pharmacophobia), positive aspects of medication (pharmacophilia), high/low psychological reactance, high/low doctor health locus of control (HLOC) and high/low internal HLOC. Based on the Beliefs about Medicines Questionnaire we have developed a measure of skepticism, defined as a patient's high concern about adverse reaction to an individual medication and a low belief in its necessity. Our research experience based on the tools for assessing and predicting adherence is presented in a practical manner by using seven boxes and examples. (Neuropsychopharmacol Hung 2021; 23(4): 336-346).

Poor Adherence to Oral Psychiatric Medication in Adults with Bipolar Disorder: The Psychiatrist May have More Influence than in Other Severe Mental Illnesses.

Objective: Medication adherence in bipolar disorder (BD) may be influenced by 6 selfreported dimensions: 1) high/low psychological reactance, 2) high/low internal healthlocus of control (HLOC), 3) high/low doctor HLOC, 4) pharmacophobia, 5) pharmacophilia, and 6) skepticism about a specific medication. This study in Spain, Argentina, and Venezuela included 142 outpatients with BD prescribed 320 psychiatric medications and 1230 other psychiatric outpatients prescribed 2134 medications. Methods: Logistic regression models included adherence for each psychiatric medication, measured by the Sidorkiewicz Adherence Tool as the dependent variable. The models provided adjusted odds ratios (ORs) of dichotomous independent variables: clinical variables and 6 self-reported dimensions. Results: ORs significant in both groups were: 1) high doctor HLOC (OR=1.87 in BD, OR=1.25 in other patients), 2) high psychological reactance (respectively OR=0.572, OR=0.798), 3) pharmacophobia (respectively OR=0.361, OR=0.614), and 4) skepticism about a specific medication (respectively OR=0.300, OR=0.556). Two ORs were only significant in BD patients: medication duration > 1 year (OR=0.449), and extreme polypharmacy (OR=2.49). The study included 104 BD patients prescribed 122 mood stabilizers and 136 other patients prescribed 140 mood stabilizers. Two ORs were significant for mood stabilizer adherence only in BD patients: high doctor HLOC and skepticism (respective ORs=2.38, OR=0.390). The study included 87 BD patients prescribed 97 antipsychotics and 417 other patients prescribed 458 antipsychotics. Four ORs were significant for antipsychotic adherence only in the BD group. Conclusions: Future studies of adherence to all/specific medications should explore the specific city/commonality of these dimensions, particularly doctor HLOC, in BD versus other psychiatric patients. (Neuropsychopharmacol Hung 2021; 23(4): 347-362).

Adherence to psychiatric medications: Comparing patients with schizophrenia, bipolar disorder and major depression.

Findings of three articles reporting results in 1372 stabilized outpatients taking 2454 medications in Spain, Argentina, and Venezuela were combined. Prevalence of good adherence was not obviously different across diagnoses: 69.5% (N=212) for schizophrenia, 66.3% (N=142) for bipolar disorder, and 69.8% (N=521) for depression. Besides the focus on stabilized outpatients, other study biases included use of a research sample; limited to oral medications, ignoring long-acting injectable antipsychotics; and lack of data on active substance abuse, clinical severity, and insight. Logistic regression models explored predictors of good vs. poor adherence. The six self-reported variables studied were pharmacophobia, pharmacophilia, high psychological reactance, high internal health locus of control (LOC), high doctor LOC, and skepticism concerning specific medications. ORs were significant in 56% (47/84) of the statistical tests vs. 24% (23/98) of ORs significant in case of 7 demographic/clinical variables (p=0.001). At least 2/3 of the ORs for pharmacophobia, pharmacophilia and skepticism were significantly associated with adherence in cases and controls, indicating their independence from diagnoses. In need of replication, three other self-reported measures had differential effects on adherence across diagnoses. High psychological reactance was associated with decreased adherence to antidepressant medications in general, or for patients with mood disorders. High internal LOC as associated with poor adherence may reflect the distrust patients with schizophrenia or severe bipolar disorder have of other people. High doctor LOC was significantly associated with increased adherence only in patients with bipolar disorder, but was significant for all medications, mood stabilizers and antipsychotics, indicating the relevance of the patient-psychiatrist relationship in these patients. (Neuropsychopharmacol Hung 2021; 23(4): 363-373).

Poor Adherence to Oral Psychiatric Medication in Adults with Depression: Psychological Reactance May Have Specific Effects in Depression.

Objective: Medication adherence in psychiatric disorders, including depression, may be influenced by 6 self-reported dimensions: 1) high/low doctor health locus of control (HLOC), 2) high/low internal HLOC, 3) high/low psychological reactance, 4) pharmacophilia, 5) pharmacophobia, and 6) skepticism about a specific medication. This study in Spain, Argentina, and Venezuela included 521 outpatients with depression prescribed 920 psychiatric medications and 851 other psychiatric outpatients prescribed 1534 medications. Methods: Logistic regression models were completed in patients with depression and psychiatric controls. The dependent variable was adherence for each psychiatric medication (Sidorkiewicz Adherence Tool). The models provided adjusted odds ratios (ORs) of dichotomous independent variables: clinical variables, and 6 self-reported dimensions. Results: ORs significant in both diagnostic groups were: 1) pharmacophobia (OR=0.500 in depression, OR=0.599 in other patients), 2) pharmacophilia (respectively OR=1.51, OR=1.65), 3) treatment for 1 year (respectively OR=0.731, OR=0.608), 4) geriatric age (respectively OR=2.28, OR=3.02), and 5) skepticism about a specific medication (respectively OR=0.443, OR=0.569). Two ORs were significant in the depression group, but not in the controls: the country of Spain (OR=0.744), and high psychological reactance (OR=0.685). The study included 470 depression patients prescribed 510 antidepressants and 348 other patients prescribed 370 antidepressants. One OR was significant for antidepressant adherence in both groups: high psychological reactance (respectively OR=0.597, OR=0.561). Conclusions: All clinical studies using self-report include biases but the most important is lack of access to patients not coming for treatment. Future studies should further explore the specificity/commonality of these dimensions, particularly psychological reactance, in depression versus other psychiatric disorders. (Neuropsychopharmacol Hung 2021; 23(4): 374-387).

Poor Adherence to Oral Psychiatric Medication in Adults with Schizophrenia May Be Influenced by Pharmacophobia, High Internal Health Locus of Control and Treatment Duration.

Objective: This study in Spain, Argentina, and Venezuela included 212 schizophrenia outpatients prescribed 387 psychiatric medications and 1,160 other psychiatric outpatients prescribed 2,067 medications. Methods: Logistic regression models included adherence for each psychiatric medication, measured by the Sidorkiewicz Adherence Tool, as the dependent variable. The models provided adjusted odds ratios (ORs) of dichotomous independent variables: 1) clinical variables, 2) subscales from the Patient Health Beliefs Questionnaire on Psychiatric Treatment (presence/absence of pharmacophobia and pharmacophilia and high/low psychological reactance, internal health locus of control [HLOC] and doctor's HLOC) and 3) presence/absence of skepticism toward each medication measured by the Beliefs about Medicines Questionnaire (BMQ). Results: ORs significant in both groups were: 1) pharmacophobia (OR=0.389 in schizophrenia, OR=0.591 in other patients and not significantly different) and 2) pharmacophilia (respectively OR=2.18, OR=1.59 and significantly higher in schizophrenia: p=0.012). Prescribing the medication for >1 year increased adherence in schizophrenia (OR=1.92) while decreasing it in others (OR=0.687). Four ORs were significant in the schizophrenia group but not in the controls: treatment for >1 year (OR=0.161), high internal LOC (OR=0.389), extreme polypharmacy (OR=1.92) and the country of Spain (OR=0.575). Regarding antipsychotics, the study included 204 schizophrenia patients prescribed 240 antipsychotic medications and 301 other patients prescribed 315 antipsychotic drugs. Three ORs were significant for antipsychotic adherence in the schizophrenia group: pharmacophobia (OR=0.324), treatment for >1 year (OR=0.362), and skepticism about specific antipsychotics (OR=0.535). Conclusions: Future adherence studies for antipsychotic/all medications should further explore the specificity/commonality of these dimensions in schizophrenia versus other psychiatric patients. (Neuropsychopharmacol Hung 2021; 23(4): 388-404).

What is the dominant treatment attitude of psychiatric patients?

Background: Patients' attitude towards drug treatment is of prognostic value regarding adherence. However, few detailed analyses have been performed regarding the influencing factors of the treatment attitude of psychiatric patients. Methods: We enrolled in the study 295 psychiatric inpatients and analyzed the data obtained using the recently developed Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT), the Behavioural Inhibition/ Activation System (BIS/BAS) Scale, and the Hospital Anxiety and Depression Scale. We created a 'dominant treatment attitude' (DTA) variable from the 5 subscales of the PHBQPT. Results: The most common DTA was the Doctor HLOC and the rarest proved to be the Psychological Reactance. The double DTA carriers were the most frequently occurring multiple DTAs. We found that the Doctor-HLOC coupled most frequently with the Positive Aspect and the DoctorHLOC with the Internal-HLOC. The Doctor-HLOC score was higher while the BAS Fun seeking score lower in the case of patients treated for affective disorders compared to patients who belonged to the psychosis and personality disorder subgroups. Conclusions: Screening of DTAs in psychiatric patients can provide useful information for the planning of a more effective therapeutic strategy. (Neuropsychopharmacol Hung 2021; 23(2): 308-318).

Health Control Beliefs and Attitude Toward Treatment in Psychiatric and Non-Psychiatric Clinical Samples.

Although there is accumulating evidence on the potential influencing factors of medication adherence, the knowledge about patients' attitudes and beliefs toward treatment is only partly utilized in adherence-improving strategies. Several internal and external factors determining adherence have been described regarding many chronic somatic diseases but in recent research, insight on psychiatric patients has been exclusively lacking. As a result, there is a scarcity of effective adherence-improving interventions. Identification of any specific differences or similarities between the attitudes toward treatment of psychiatric and non-psychiatric patients would help to support adherent behavior. We recruited 189 participants from four departments of general psychiatry (GEN PSYCH, n = 106), addictology (ADDICT, n = 42) and somatic diseases (NON PSYCH, n = 41). The Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) was performed to assess the patients' attitude toward drug treatment, perceived health locus of control, and psychological reactance. The most robust difference of the PHBQT scores occurred between the GEN PSYCH and ADDICT subgroups. ADDICT patients scored significantly higher on the internal and external health locus of control and on the Psychological Reactance subscale as well. While GEN PSYCH subjects provided higher scores on the Positive Aspect of Medication compared to ADDICT persons. Interestingly, the only difference between the GEN PSYCH and NON-PSYCH groups was the more pronounced mistrust in physicians in the case of psychiatric patients. Our data suggest that mistrust toward medication does not differ in psychiatric and non-psychiatric samples, while the acceptance of the doctor's competency may be stronger in the non-psychiatric sample. The analysis of these factors provides information which could help us better understand this important issue and to develop more efficient interventions for improving adherence.

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.

[Validation and analysis of the Patient's Health Belief Questionnaire on Psychiatric Treatment in a sample of Hungarian psychiatric patients].

OBJECTIVES: Patients' attitude towards treatment is one of the most signifi cant factors which has determining eff ect on suffi cient adherence. Data are lacking on Hungarian patients' attitude towards psychiatric treatment, however, high prevalence of suicide suggests that eff ectiveness of psychiatric treatments need to be improved. To pave the way for such studies, we performed the validation of the recently developed Patients' Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) in a sample of Hungarian psychiatric patients. METHODS: We enrolled 188 Hungarian patients diagnosed with psychiatric disorders. The PHBQPT was translated into Hungarian by our group. Comparison of item and subscale mean scores with the original data are presented. Internal consistency, item-total and item-item correlations were calculated and factorial structure was analysed. RESULTS: Single item means, the highest item score and subscale mean scores were similar to data published in the original article. The factorial analysis confi rmed the validity of a fi ve-subscale structure in our sample. The eff ects of gender and age were not signifi cant on any of the subscales. CONCLUSIONS: The PHBQPT is a valid, reliable instrument with replicable psychometric properties. The Hungarian version is suitable for clinical practice and for further investigations on attitudes towards psychiatric treatment.

Genetic analyses of the endocannabinoid pathway in association with affective phenotypic variants.

BACKGORUND: Increasing experimental data confirm the crucial role of the endocannabinoid (eCB) system in the regulation of stress response and emotional processes. Despite of the fact, that genetically determined vulnerability for stress is a widely accepted concept in the pathomechanism of affective disorders, replicable human genetic results with interaction analyses of early life trauma and eCB genes are rare. The aim of this study is to test the associations between genetic variants of the eCB pathway, childhood trauma and affective phenotypes. METHODS: We selected 18,897 SNPs in the eCB pathway of a GWAS dataset in two general population cohorts (BP sample N = 837; MN sample N = 988). Association analyses were performed on the anxious and depressive subscales of the Brief Symptom Inventory (BSI-ANX and BSI-DEP, respectively). Childhood trauma was assessed by the Childhood Adversity Questionnaire (CAQ). Association analyses were performed in the R 2.0. statistical program using the SNPassoc package. REULTS: Genetic effect was more robust in the BP sample than in the MN sample. The most comprehensive results showed that SNPs in the CACNA1C gene associated with depressive phenotype in interaction with CAQ in both BP (p = 1.2 × 10-4) and MN samples (p = 1.6 × 10-4). Direct association analyses (without interaction) provided significant associations between SNPs in different genesets of the two study populations. SNPs in KCNJ3 and GNB5 genes on the BSI-DEP (p = 6.1 × 10-5; p = 7.1 × 10-4) and GNG12 gene on the BSI-ANX (p = 7.4 × 10-6) in the BP sample, while GABAergic, ADCY1 and HTR2A gene variants can be outlined from results of MN sample with less strong p-values. CONCLUSION: Our results confirmed the prominent role of CACNA1C gene in the pathogenic effect of early life stress in the development of affective vulnerability in two different study populations using GxE interaction analysis. CACNA1C gene, as it encodes for L-type voltage-gated calcium channel, contributes to neuronal excitability, plasticity and neurogenesis being a crucial effector of both eCB signaling and the BDNF-CREB pathway as well. Our findings suggest that childhood trauma related depression may have more robust genetically determined basis than without early life stress.

[The first lockdown due to COVID-19 pandemic from the psychiatric patients' perspective: an ambulatory care client experience survey]. / A COVID-19 járvány miatt elrendelt elso veszélyhelyzet a pszichiátriai betegek szemszögébol: gondozói felmérés.

INTRODUCTION: The coronavirus pandemic (COVID-19) required the declaration of a state of emergency in Hungary from 11 March 2020 to 18 June 2020. These governmental actions led to changes in everyday life, implementation of new rules, and reduced access to healthcare. Hospital beds were reserved for emergency use, face-to-face ambulatory care was mainly replaced by telemedicine. In our study we assessed opinion of the patients in two outpatient psychiatric care units in Budapest regarding the state of emergency. METHODS: We enrolled 438 patients in the survey (305 women and 133 men, mean age: 51.9±16.2 years). The patients completed a short questionnaire on a voluntary and anonymous basis following verbal informed consent. The questionnaire was comprised of 10 items and a 12-item "Problem Evaluation Scale" (fear, isolation and healthcare subscales). The comparison of groups was done using general linear models (GLM), pairwise comparison was performed using Tukey's test for post hoc analysis. The data set was analyzed with SPSS software, version 24.0. RESULTS: Up to 34% of enrolled patients believed that their condition worsened during the state of emergency, but 12% of these patients thought that this worsening was not related to the state of emergency. Twice as many patients (12.8%) were concerned about their financial situation than about their health status (6.1%). Loneliness and the implementation of specific regulations didn't cause relevant distress in almost half of the patients, isolation was the most frequently (55.2%) reported difficulty. The worsening of health status was reported more frequently (p=0.001) by the patients younger than 50 years, the sensation of fear was stronger (p=0.045), and they reported more serious adaptation difficulties (p=0.003) than subjects older than 50 years. Isolation caused significantly (p=0.003) more serious distress among women. The abundance of pandemic-related information caused more distress in the case of patients treated for anxiety than participants treated for psychotic disorders (p=0.024). Patients suffering from affective disorders perceived more pronounced feelings of vulnerability compared to patients treated for psychotic disorders (p=0.004). CONCLUSION: Approximately half of the enrolled psychiatric patients was able to adapt to this situation without major difficulties, the other half of this sample was more or less distressed by these circumstances. Unfortunately, depletion of emotional, psychological, social and material resources can be expected during the next stage of the pandemic. As a result, we can expect further worsening of the above presented aspects.

[Acute effects of the first period of COVID-19 pandemic on mental state]. / A COVID-19 pandémia akut hatásai a pszichés állapotra a járvány elso szakaszában.

The COVID-19 pandemic causes psychological trauma in the whole society, thus investigation of the epidemiology of psychiatric symptoms is an outstanding research field during this period. Fear of infection, exposure to updated data on death figures, social isolation, adaptation to new restricting rules, existential crisis, reduction of health care availability poses dangers for mental health. Currently published papers focus on the acute effect of first wave of COVID-19 pandemic, however, further studies on long-term consequences can make this picture more complex and sophisticated. In this review a summary is provided on the most important results concerning frequency of psychiatric symptoms during the first lockdown of COVID-19. In light of the results it can be stated that psychiatric patients showed more common and more intensive symptoms, the number of relapses is increased and the adherence is reduced. Notably, more than the half of the general population produced measurable psychiatric symptoms. Furthermore, a worrying portion of frontline healthcare workers started manifesting mental symptoms. The overall picture suggests that the mental health state shows a global decline on the level of the general society which highlights the urgent need for targeted and complex mental support programs.

[Health control beliefs and chronic illness:how do they relate?] / Egészségkontrollhit és krónikus betegség:hogyan hatnak egymásra?

The health locus of control has been extensively analyzed in diff erent patient populations suff ering from chronic somatic illnesses due to its infl uence on adherence to long-term therapies. Despite of the fact that adherence is one of the most important factors which needs to be taken into consideration in the oupatient care of psychiatric patients, there is a scarcity of studies regarding HLOC in this population. In this review we provide an overview of study results regarding HLOC in somatic and psychiatric patients. Based on these results we conclude that in the case of patients suff ering from chronic illnesses, a higher internal HLOC is associated with less severe depressive symptoms and better adherence and quality of life. Nevertheless, the results of the follow-up studies indicate that change of HLOC (from internal to external) can be adaptive when the outcome is not favourable or the treatment is not eff ective. The continuous evaluation of HLOC of psychiatric patients in treatment may provide necessary information for the planning of interventions to help this process. Taking into consideration that the patients' perception of control is often impaired due to the nature of psychiatric illnesses we propose evaluation of psychobiological factors infl uencing health locus of control in order to facilitate the planning of these interventions.

[The role of nutritional factors in the adjuvant treatment of major depressive disorder].

A growing body of data has accumulated in the past decades about the possible role of nutritional factors in influencing the initiation and course of mental disorders as well as in the treatment of these disorders. As a result of the aggregation of this data a new field emerged - "nutritional psychiatry". In our current review paper we discuss some of those natural agents that supposedly have antidepressive properties and, accordingly, may play a role in the stand-alone and/or adjuvant treatment of major depressive disorder.

[Paternal depression in a "stay-at-home" father - case report]. / Apai GYES-depresszió? Esettanulmány.

There is a growing body of data on paternal peripartum depression (perinatal depression in father; PND-F), however, it has traditionally been investigated only in women. Recently accumulating results confirmed the prominent role of the mental health of fathers in the psychosocial development of children and new trends showed up concerning the father's role in the family. In this case report we demonstrate the clinical aspect of a depressive episode of a "stay-at-home" father of two children (a 5-year old boy living with autism and a 8-year old girl). In relation to the case we want to emphasize that various situations can be stressful for a person with affective vulnerability. It is noteworthy that although childcare is a happy period for the majority, it can be a stressful life period for vulnerable persons and it can provoke a depressive episode. Acceptance and tolerance of this correlation at the level of society is still far away, however, it is indispensible for adequate and timely intervention which is essential for the stability of families and the psychosocial development of children.