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.

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression.

Accelerated repetitive transcranial magnetic stimulation (rTMS) protocols are being increasingly studied because of their potential to provide quicker and enhanced treatment efficacy. However, there is a lack of accelerated deep TMS with H1-coil (adTMS) treatment research. This randomized pilot study investigated the efficacy and safety of adTMS protocols. Twenty-eight TRD patients received 20-min sessions twice daily for 10 or 15 days. Primary outcomes were changes in Hamilton Depression Rating Scale (HDRS) scores and discontinuation because of adverse events (AE). Secondary outcomes were response, remission, daily changes in Beck Depression Inventory-II (BDI-II) scores, and AE incidence. HDRS scores decreased by 13 (95% CI 11-17; 59%, 95% CI 45-73%) and 13 (95% CI 11-14; 62%, 95% CI 54-69%) points in the 10- and 15-day protocols, respectively. The adjusted difference between the two protocols was not significant or clinically relevant. Remission was achieved by 38% and 42% after 10-day and 15-day protocols, respectively. The intervention was discontinued because of AEs in 3/33 (9%) patients. The BDI-II decreases were significant and clinically relevant during the first 8 days. Twice-daily adTMS for 10 days seems to be safe and effective, with rapid clinical benefits during the first week of treatment. These promising results warrant further investigation in larger randomized clinical trials comparing adTMS with the standard dTMS protocol.

Salivary cortisol response to psychosocial stress in patients with first-episode psychosis.

AIM: To analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group. METHODS: We performed a cross-sectional analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool. RESULTS: Patients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test. CONCLUSION: Patients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.

Integration of complementary biomarkers in patients with first episode psychosis: research protocol of a prospective follow up study.

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.