Overview of Studies on the Efficacy of Repetitive Transcranial Magnetic Stimulation on the Severity of Symptoms of Major Depressive Disorder, Conducted in University Psychiatric Hospital Sveti Ivan 2016-2022.

This brief report presents the studies on HF rTMS efficacy on major depressive disorder (MDD) symptoms conducted in University Psychiatric Hospital Sveti Ivan from 2016 to 2022. We assessed the clinically relevant effects of rTMS delivered by H1-coil and the figure-8-coil on MDD symptoms severity in the pooled sample of patients. During the last seven years, we enrolled in the studies on MDD 336 patients with a median (interquartile range; IQR) age of 53 (45-61) years, 181 (54%) of them women. We performed interventions with two different coils (8-coil and H1-coil) at 120% of the motor threshold, approximately half with 10 and half with 18 Hz frequency, and > 90% with one daily session during 20 workdays. We offer considerations on how the bulk of our research informed the future direction of our laboratory's studies and clinical work.

Hyperprolactinemia - side effect or part of the illness.

BACKGROUND: Hyperprolactinemia is associated with side effect of antipsychotics in people suffering from psychotic disorders. However, increased prolactin levels (mlU/L) were found in patients suffering from the first psychotic episode who were not receiving antipsychotic therapy. The assumption of this study is that the abnormality in the level of prolactin is associated with the effect and influence of the disease, not the therapy that is carried out. SUBJECTS AND METHODS: Study involved 54 female patients hospitalized in Psychiatric hospital "Sveti Ivan", whose average age was 33.9 years. All patients had been diagnosed with a psychotic disorder (according to MKB-10, F20-F29). 18 patients had their first psychotic episode, while 36 patients had relapses of psychotic disorder. The methods used were: PANSS scale and measurement of prolactin concentration (Immunoanalyzer ACCESS 2, CLIA method). Arithmetic mean, standard deviations, correlation coefficient, Mann Whitney U test and the chi-squared test were used. RESULTS: 75.5% of patients had prolactin values above the reference values (min 121, max 4192 ml/L). In a sample of patients with first psychotic episode, 77.8% had elevated prolactin levels, while among re-hospitalized patients, elevated levels had 74.2%. Statistically significant results were obtained: patients with higher pronounced symptoms had higher prolactin values, especially particles on PANSS: P1 (delusions), N4 (Apathy), G15 (preoccupation) and G16 (active avoidance). CONCLUSION: Elevated prolactin in patients has been demonstrated regardless of antipsychotic therapy, therefore the question of etiology of hyperprolactinemia in psychotic disorders is questionable. The association of hyperprolactinemia with the severity of the clinical picture has also been demonstrated, higher prolactin values indicating a stronger clinical picture, which calls into question the protective role of prolactin in psychotic disorders.

Trace elements concentrations association with schizophrenia symptoms; A cross-sectional study in Croatia.

BACKGROUND: Significant inconsistencies exist in findings on association of bio-elements (BE) concentrations and schizophrenia. Hypothesis of this research was that different concentrations of BE are associated with different psychopathological schizophrenia symptoms. SUBJECTS AND METHODS: This cross-sectional study was performed from 2014 to 2016 at Psychiatric Hospital "Sveti Ivan" and University Psychiatric Hospital "Vrapce", Zagreb, Croatia, on the consecutive sample of 67 patients diagnosed with schizophrenia. BE concentrations were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) at the Institute for Medical Research and Occupational Health in Zagreb. Severity of schizophrenia symptoms was assessed on Brief Psychiatric Rating Scale (BPRS). RESULTS: After adjustment for all preplanned possible confounding variables, the first canonical correlation between BE and BPRS dimensions variates were statistically significant (Rc2=0.73; P=0.006). The first pair of canonical variates is defined by BPRS negative dimension (and marginally by positive symptoms and lack of resistance), and copper (Cu), lead (Pb), lithium (Li) and cobalt (Co) (marginally by cadmium (Cd) and nickel (Ni)). CONCLUSIONS: Concentrations of different BE are associated with different schizophrenia symptoms. Maximal correlation between BPRS and BE may be achieved with the weighted linear composite of negative schizophrenia symptoms and copper (Cu), lead (Pb), lithium (Li) and cobalt (Co).

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

BACKGROUND: There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). SUBJECT AND METHODS: We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. RESULTS: Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). CONCLUSIONS: In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Sex and gender differences in cancer in individuals with severe mental disorders.

PURPOSE OF REVIEW: Although cancer incidence is similar between individuals with severe mental disorders (SMD) and the general population (GP), survival rates are lower, particularly in those with schizophrenia. While the scientific and medical communities acknowledge sex differences in cancer mechanisms, including risk factors and cancer types, less is known about sex and gender disparities in incidence, mortality, and care pathways among those with SMD. This review aims to explore these differences in cancer among individuals with SMD. RECENT FINDINGS: Current evidence on sex and gender differences in cancer care for SMD is limited. It is unclear how these factors affect cancer incidence and mortality in the SMD population, and if they correspond to those in the GP. The literature frequently omits detailed information on sex-based differences in SMD-related cancer rates, complicating conclusive analysis. Moreover, people with SMD experience significant challenges in accessing cancer screenings compared to the GP, and findings on sex and gender disparities in this context remain inconclusive. SUMMARY: This review emphasizes that while significant sex and gender-based differences in cancer mechanisms, incidence, and survival exist within the GP, they have not been fully integrated into clinical practice. It underscores the need of addressing these differences in cancer incidence, outcomes, mortality, and care pathways to enhance treatment for individuals with SMD.

Prevalence of posttraumatic stress disorder following acute coronary syndrome and clinical characteristics of patients referred to cardiac rehabilitation.

BACKGROUND: Studies have demonstrated that patients who have experienced acute coronary syndrome (ACS) have an increased risk of developing posttraumatic stress disorder (PTSD) and experiencing worse survival outcomes than those who do not develop PTSD. Nevertheless, the prevalence rates of PTSD following ACS vary widely across studies, and it is noteworthy that in most cases, the diagnosis of PTSD was based on self-report symptom questionnaires, rather than being established by psychiatrists. Additionally, the individual characteristics of patients who develop PTSD after ACS can differ widely, making it difficult to identify any consistent patterns or predictors of the disorder. AIM: To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation (CR) after ACS, as well as their characteristics in comparison to a control group. METHODS: The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia, the Special Hospital for Medical Rehabilitation Krapinske Toplice. Patient recruitment for the study took place over the course of one year, from January 1, 2022, to December 31, 2022, with a total of 504 participants. The expected average follow-up period for patients included in the study is about 18 mo, and currently ongoing. Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview, a group of patients with a PTSD diagnosis was identified. From the participants who do not have a PTSD diagnosis, patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups. RESULTS: A total of 507 patients who were enrolled in the CR program were approached to participate in the study. Three patients declined to participate in the study. The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients. Out of the total sample of 504 patients, 74.2% were men (n = 374) and 25.8% were women (n = 130). The mean age of all participants was 56.7 years (55.8 for men and 59.1 for women). Among the 504 participants who completed the screening questionnaire, 80 met the cutoff criteria for the PTSD and qualified for further evaluation (15.9%). All 80 patients agreed to a psychiatric interview. Among them, 51 patients (10.1%) were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria. Among the variables analyzed, there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups. Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group (P = 0.035). CONCLUSION: The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment. Furthermore, the data suggest that these patients may exhibit reduced physical activity levels, which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population. Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.

Antipsychotics-induced hyperprolactinemia and screening for macroprolactin.

INTRODUCTION: High prolactin (PRL) concentrations are found in laboratory test results of patients on majority of antipsychotic drugs. Prevalence rates and degrees of severity of hyperprolactinemia (HPRL) based on PRL concentration may depend on the presence of macroprolactin in the serum. The aim of the study was to investigate the difference between PRL concentrations before and after precipitation of macroprolactin and to examine if there were any changes in the categorization of HPRL between samples prior and after precipitation. MATERIALS AND METHODS: Total of 98 female patients (median age 33; range 19-47 years) diagnosed with a psychotic disorder, proscribed antipsychotic drugs, and with HPRL were included. Total PRL concentration and PRL concentration after macroprolactin precipitation with polyethylene glycol (postPEG-PRL) were determined by the chemiluminometric method on the Beckman Coulter Access2 analyser. RESULTS: Total PRL concentrations (median 1471; IQC: 1064-2016 mlU/L) and postPEG-PRL concentrations (median 1453; IQC: 979-1955 mlU/L) were significantly correlated using intraclass correlation coefficient for single measurements (mean estimation 0.96; 95%CI 0.93-0.97) and average measurement (mean estimation 0.98; 95%CI 0.96-0.99), and all investigated female patient had HPRL according to PRL and postPEG-PRL concentration. The median PRL recovery following PEG precipitation was 95; IQC: 90-100%. There was substantial agreement (kappa test = 0.859, 95% CI: 0.764-0.953) between the categories of HPRL severity based on total PRL concentrations and postPEG-PRL concentrations. CONCLUSION: The study demonstrated that HPRL was present in all subjects using the reference interval for total PRL concentration and postPEG-PRL concentration with no significant impact of macroprolactin presence in the serum on the categorization of patients according to severity of HPRL.