Water-Wave Vortices and Skyrmions.

Topological wave structures-phase vortices, skyrmions, merons, etc.-are attracting enormous attention in a variety of quantum and classical wave fields. Surprisingly, these structures have never been properly explored in the most obvious example of classical waves: water-surface (gravity-capillary) waves. Here, we fill this gap and describe (i) water-wave vortices of different orders carrying quantized angular momentum with orbital and spin contributions, (ii) skyrmion lattices formed by the instantaneous displacements of the water-surface particles in wave interference, and (iii) meron (half-skyrmion) lattices formed by the spin-density vectors, as well as (iv) spatiotemporal water-wave vortices and skyrmions. We show that all these topological entities can be readily generated in linear water-wave interference experiments. Our findings can find applications in microfluidics and show that water waves can be employed as an attainable playground for emulating universal topological wave phenomena.

The Use of eHealth for Pharmacotherapy Management With Patients With Respiratory Disease, Cardiovascular Disease, or Diabetes: Scoping Review.

BACKGROUND: eHealth is increasingly considered an important tool for supporting pharmacotherapy management. OBJECTIVE: We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management. METHODS: We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends. RESULTS: Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes. CONCLUSIONS: There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.

Aging Brain, Dementia and Impaired Glymphatic Pathway: Causal Relationships.

Cellular and molecular processes that are of key importance in the development of neuroinflammation and increased cytokine response, activation of microglia and astrogliosis, contributing to the accumulation of metabolites and aberrant proteins in the brain tissue due to their overproduction and insufficient clearance, concomitant disturbance of architecture and sleep patterns are interconnected and induce brain aging with the formation its complex neurobiological mechanism. The study of these processes brings us closer to understanding the main determinants of healthy and unhealthy aging, primary prevention and preclinical diagnosis of age-related diseases, as well as to solving problems of longevity and increasing quality of life. The imbalance of homeostatic functions that support the exchange of fluids and solutes in the brain tissue is observed both in physiological aging and in the development of pathology of the nervous system with long-term consequences - from impaired synaptic signaling to the development of neurodegenerative diseases. Dementia is one of the major health problems worldwide and is very complex in terms of pathophysiology. Therefore, one of the priorities of fundamental neurobiology is to elucidate the main morbid mechanisms of Alzheimer's disease as the most common form of dementia. The hypotheses of ß-amyloid and tau protein largely explain the main pathological features of Alzheimer's disease, however, there remains a need for further research on biomarkers with high validity and predictive applicability in people without cognitive impairment and clinical symptoms and in the early stages of the disease. There is a need to intensify the search for effective solutions to slow or stop the progression of the disease, especially therapeutic approaches that modify the disease at the preclinical stage, when it is most beneficial to change its course. At the same time, the discovery of aquaporin-dependent clearance pathways in the brain made it possible to identify new mechanisms underlying the etiology and progression of neurodegeneration and neuroinflammation. Glial-mediated clearance plays a fundamental role in the process of physiological aging, the development of age-related changes in the brain, and neurodegenerative processes. We analyzed 273 articles posted in PubMed database selected by keywords "glymphatic system, Alzheimer's disease, dementia, amyloid Aß, aquaporin, aging, brain clearance". A total of 102 full-text articles were included in this review. This article presents up-to-date evidence on the causes and consequences in the study of the relationship between dysfunction of the glymphatic pathway and the accumulation of pathological proteins with insufficient excretion of toxic metabolites from the brain parenchyma, which is considered a key factor in the development of Alzheimer's dementia.

G.T. MSRS On-Line Calculator Targeting the Early Diagnosis of Mixed Affective States: the Multicenter Study Project Design on the Approbation and Validity of the Three Language Versions of the Rating Scale.

BACKGROUND: Mixed affective states (MS) are often misdiagnosed by the clinicians and lead to the inappropriate treatment strategies contributing to the severe forms, poor outcome with higher rates of comorbid conditions and worse remission quality in affective and bipolar disorders, as well as to a decreased psychosocial functioning of these patients. The development of reliable tools for the MS assessments or so called the phenomenon of mixity in affective disorders, is still an unmet need of psychiatric research and clinical practice. In this paper, we present PC program "Multilingual IBM-PC on-line calculator for early diagnosis of the mixed affective states" based on the Giuseppe Tavormina Mixed States Rating Scale (G.T. MSRS) (Russian, English, Italian language versions) created by the ICERN group using programming language JavaScript, working for such operation systems (OS) as Windows, Linux, MacOs, Android, iOS, and aims to contribute to the accurate assessment of the presence and severity of the mixed states among affective disorders. SUBJECTS AND METHODS: The G.T. Mixed States Rating Scale on-line calculator consists of 11 items which evaluate various aspects of MS in patients with major depression, bipolar or recurrent depressive disorder. A total score is automatically calculated, considering the type of affective temperament according to the Akiskal's and Tavormina's schemas, thus, the specific sub-groups of MS are differentiated based on the ranges: Medium-light (2-6), Medium (7-12), and High (13-19) Mixity level. The study will enroll 330 participants during two (three months follow-up) visits (110 native speakers in each of the three languages) of both genders aged from 18 till 55 y.o. with the diagnoses of depressive episodes, major depression, bipolar or recurrent depressive disorder according to the DSM-5 criteria. Assessments will be provided by the two investigators (second one will be blinded to the G.T. MSRS results obtained by the first researcher), based on the use of DSM-5 clinical interview, Young Mania Rating Scale, Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression - Severity scale (CGI-S), Clinical Global Impression - Improvement scale (CGI-I), Patient Global Impression of Change (PGIC). RESULTS: The study will assess the agreement between the diagnostic category/clinical impression and the on-line G.T. MSRS calculator use results, its test-retest reliability, and diagnosis stability for further assessment of the on-line G.T. MSRS calculator validity and clinical utility. Secondary variables will evaluate internal reliability and such statistical analyses as Cronbach's alpha, Cohen's Kappa, biserial correction, and agreement between initial and follow-up diagnoses. CONCLUSIONS: Current multicenter validation study of the on-line G.T. MSRS calculator will enhance the understanding of the mixity phenomenon and its clinical implication, aiming to improve the treatment strategies to manage the course of mental disorder, quality of life and psychosocial functioning in patients with affective (bipolar) disorders, accompanied by MS, and a clinical recommendation for the routine administration of the user-friendly on-line G.T. MSRS version in clinical practice.

Beliefs in Conspiracy Theories and Mental Health in the Student Community of Latvia During the COVID-19 Outbreak.

BACKGROUND: The objective of this study was to investigate self-reported changes in mental health and their association with various sociodemographic factors and beliefs in conspiracy theories among university and college students in Latvia during the second state of emergency caused by COVID-19. SUBJECTS AND METHODS: This cross-sectional study was conducted as part of an international research project, where university and college students were anonymously asked to complete an online self-report questionnaire. Changes in anxiety and depression were assessed using self-rated questions. Statistical analysis involved Pearson's chi-square test and univariate binary logistic regression.ression. RESULTS: The study comprised 1047 students, with 828 females (79.08% aged 21.71±0.09). Worsening in self-reported anxiety was more prevalent among females (69.3%, p<0.001), unemployed respondents (70.0%, p=0.003), individuals who were were not working during the lockdown (70.3%, p<0.001), those experiencing deterioration in general health condition (93.0%, p<0.001), and those belonging to or having knowledge of someone in a vulnerable group (69.5%, p=0.004). Worsening self-reported depression was more prevalent in respondents who did not work during the lockdown (63.9%, p=0.014) and those with deteriorating general health conditions (93.0%, p<0.001). Increased odds ratios (OR) for experiencing changes in anxiety and depression were associated with beliefs in the following conspiracy theories: 'Recommended measures are an attempt to restrict human rights' (OR=1.49, p=0.019 and OR=2.40, p<0.001, respectively). Furthermore, increased OR for experiencing changes in depression were associated with beliefs in the following conspiracy theories: 'The COVID-19 vaccine was ready before the virus spread' (OR=3.11, p=0.007), 'COVID-19 has a lower mortality rate" (OR=1.85, p<0.001)', 'Recommended measures are an attempt to restrict human rights' (OR=2.40, p<0.001), and 'The COVID-19 outbreak is the creation of world leaders' (OR=2.17, p=0.003). CONCLUSIONS: Self-reported changes in depression and anxiety were associated with certain beliefs in specific conspiracy theories.

Comparing the Anti-Depressive Effect of Electroconvulsive Therapy (ECT) Versus Transcranial Magnetic Stimulation (TMS) in the Treatment of Patients with Depression.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for depressive disorders. However, ECT has a number of limitations, such as significant side effects in the neurocognitive domain and the requirement for general anesthesia. Transcranial magnetic stimulation (TMS) is an intervention that applies electric stimulation to the brain without causing convulsions, thus representing an attractive alternative to ECT. The aim of our study is to review systematic reports of the effectiveness of ECT and TMS in the treatment of depressive spectrum disorders. SUBJECTS AND METHODS: We performed search queries in PubMed and eLibrary databases, which retrieved 391 articles, of which 14 met our inclusion criteria for the analysis. The articles comprised three comparisons: TMS vs SHAM, ECT vs sham ECT (SECT), and ECT vs PHARM. The protocol parameters analyzed for TMS were coil type, targeted brain area, amplitude of resting motor threshold, duration of session, number of sessions in total and per week, number and pulses per session and inter-train pause. For ECT, we evaluated the type of ECT device, targeted brain area, type of stimuli, and for ECT vs PHARM we recorded types of anesthesia and antidepressant medication. RESULTS: Three of 6 studies showed a therapeutic effect of TMS compared to placebo; efficacy was greater for TMS frequency exceeding 10 Hz, and with stimulation of two areas of cerebral cortex rather than a single area. There was insufficient data to identify a relationship between the success of TMS and intertrain pause (IP). Three of four studies showed a therapeutic effect of ECT compared to placebo. Three studies of bilateral ECT showed a significant reduction in depression scores compared to the SECT groups. ECT protocols with brief pulses were generally of lesser efficacy. Four of 5 ECT vs PHARM studies showed superior efficacy of ECT compared to PHARM. Among several antidepressants, only the ketamine study showed greater efficacy compared to ECT. CONCLUSIONS: There of six TMS studies and 7 of 9 ECT studies showed efficacy in reducing depressive symptoms. A prospective study of crossover design might reveal the relative efficacies of ECT and TMS.

Neuronetwork Approach in the Early Diagnosis of Depression.

BACKGROUND: Depression is a common mental illness, with around 280 million people suffering from depression worldwide. At present, the main way to quantify the severity of depression is through psychometric scales, which entail subjectivity on the part of both patient and clinician. In the last few years, deep (machine) learning is emerging as a more objective approach for measuring depression severity. We now investigate how neural networks might serve for the early diagnosis of depression. SUBJECTS AND METHODS: We searched Medline (Pubmed) for articles published up to June 1, 2023. The search term included Depression AND Diagnostics AND Artificial Intelligence. We did not search for depression studies of machine learning other than neural networks, and selected only those papers attesting to diagnosis or screening for depression. RESULTS: Fifty-four papers met our criteria, among which 14 using facial expression recordings, 14 using EEG, 5 using fMRI, and 5 using audio speech recording analysis, whereas 6 used multimodality approach, two were the text analysis studies, and 8 used other methods. CONCLUSIONS: Research methodologies include both audio and video recordings of clinical interviews, task performance, including their subsequent conversion into text, and resting state studies (EEG, MRI, fMRI). Convolutional neural networks (CNN), including 3D-CNN and 2D-CNN, can obtain diagnostic data from the videos of the facial area. Deep learning in relation to EEG signals is the most commonly used CNN. fMRI approaches use graph convolutional networks and 3D-CNN with voxel connectivity, whereas the text analyses use CNNs, including LSTM (long/short-term memory). Audio recordings are analyzed by a hybrid CNN and support vector machine model. Neural networks are used to analyze biomaterials, gait, polysomnography, ECG, data from wrist wearable devices, and present illness history records. Multimodality studies analyze the fusion of audio features with visual and textual features using LSTM and CNN architectures, a temporal convolutional network, or a recurrent neural network. The accuracy of different hybrid and multimodality models is 78-99%, relative to the standard clinical diagnoses.

Peripheral Blood Mononuclear Cell-Related Biomarkers in Schizophrenia.

INTRODUCTION: Schizophrenia is a severe mental illness causing significant impairment in personal, family, social, educational, occupational, and other important areas of life. While there is no widely accepted endophenotype, peripheral blood cells may serve as an accessible model of intracellular changes in schizophrenia. METHODS: We reviewed the literature on the query "peripheral blood mononuclear cells AND schizophrenia" in Medline (Pubmed), selecting studies that searched for specific biomarkers of schizophrenia. We considered both diagnostic biomarkers and biomarkers of therapeutic response, specific schizophrenia disorders or differential diagnostic biomarkers. RESULTS: We retrieved 41 articles matching the search criteria, among which were studies that considered changes in the production of pro-inflammatory and anti-inflammatory markers, proteins, receptors, enzyme activity, and gene expression as potential biomarkers. CONCLUSION: Approaches analysing a biological axis or a group of related biomarkers may hold the greatest promise for identifying schizophrenia. In addition, pharmacological status, smoking status, inflammatory markers and glucose metabolites, the presence of comorbidities should be considered. Certain biomarkers, while not specific for the diagnosis of schizophrenia, may indicate the prognosis and effectiveness of treatment in the established diagnosis.

Post-COVID Neuropsychiatric Complications in Children and Adolescents: a Study Design for Early Diagnosis and Treatment Using Innovative Technologies.

BACKGROUND: The COVID-19 pandemic has had significant impacts on the child and adolescent population, with long-term consequences for physical health, socio-psychological well-being, and cognitive development, which require further investigation. We herein describe a study design protocol for recognizing neuropsychiatric complications associated with pediatric COVID-19, and for developing effective prevention and treatment strategies grounded on the evidence-based findings. METHODS: The study includes two cohorts, each with 163 participants, aged from 7 to 18 years old, and matched by gender. One cohort consisted of individuals with a history of COVID-19, while the other group presents those without such a history. We undertake comprehensive assessments, including neuropsychiatric evaluations, blood tests, and validated questionnaires completed by parents/guardians and by the children themselves. The data analysis is based on machine learning techniques to develop predictive models for COVID-19-associated neuropsychiatric complications in children and adolescents. RESULTS: The first model is focused on a binary classification to distinguish participants with and without a history of COVID-19. The second model clusters significant indicators of clinical dynamics during the follow-up observation period, including the persistence of COVID-19 related somatic and neuropsychiatric symptoms over time. The third model manages the predictors of discrete trajectories in the dynamics of post-COVID-19 states, tailored for personalized prediction modeling of affective, behavioral, cognitive, disturbances (academic/school performance), and somatic symptoms of the long COVID. CONCLUSIONS: The current protocol outlines a comprehensive study design aiming to bring a better understanding of COVID-19-associated neuropsychiatric complications in a population of children and adolescents, and to create a mobile phone-based applications for the diagnosis and treatment of affective, cognitive, and behavioral conditions. The study will inform about the improved management of preventive and personalized care strategies for pediatric COVID-19 patients. Study results support the development of engaging and age-appropriate mobile technologies addressing the needs of this vulnerable population group.

Boosting topological zero modes using elastomer waveguide arrays.

We employ the Su-Schrieffer-Heeger model in elastic polymer waveguide arrays to design and realize traveling topologically protected modes. The observed delocalization of the optical field for superluminal defect velocities agrees well with theoretical descriptions. We apply mechanical strain to modulate the lattices' coupling coefficient. This work demonstrates a novel, to the best of our knowledge, platform for rapid prototyping of topological photonic devices and establishes strain-tuning as a viable design parameter for topological waveguide arrays.

Discovery and In Vivo Efficacy of Trace Amine-Associated Receptor 1 (TAAR1) Agonist 4-(2-Aminoethyl)-N-(3,5-dimethylphenyl)piperidine-1-carboxamide Hydrochloride (AP163) for the Treatment of Psychotic Disorders.

Starting from a screening hit, a set of analogs was synthesized based on a 4-(2-aminoethyl)piperidine core not associated previously with trace amine-associated receptor 1 (TAAR1) modulation in the literature. Several structure-activity relationship generalizations have been drawn from the observed data, some of which were corroborated by molecular modeling against the crystal structure of TAAR1. The four most active compounds (EC50 for TAAR1 agonistic activity ranging from 0.033 to 0.112 µM) were nominated for evaluation in vivo. The dopamine transporter knockout (DAT-KO) rat model of dopamine-dependent hyperlocomotion was used to evaluate compounds' efficacy in vivo. Out of four compounds, only one compound (AP163) displayed a statistically significant and dose-dependent reduction in hyperlocomotion in DAT-KO rats. As such, compound AP163 represents a viable lead for further preclinical characterization as a potential novel treatment option for disorders associated with increased dopaminergic function, such as schizophrenia.

What you see is what you get? Association of belief in conspiracy theories and mental health during COVID-19.

Background: The COVID-19 pandemic brought about great uncertainty and significant changes in our people's everyday lives. In times of such crises, it is natural to seek explanations to overcome our fears and uncertainties, contributing to an increase to believe in conspiracy theories which, by yielding explanations, decrease uncertainty and ambiguity and may thus have an effect on mental well-being. In spite of this, the majority of research on conspiracy theories focused on their social effects with little attention to psychological effects. Thus, the aim of our present study was to examine the association between belief in conspiracy theories and different aspects of mental health during the COVID-19 pandemic in a general population sample. Methods: Our analyses included data from the Hungarian leg of the COMET-G (COVID-19 MEntal health international for the General population) study. The Hungarian sample included participants who completed a detailed questionnaire assessing belief in seven conspiracy theory items, as well as STAI-S and CES-D to measure state anxiety and depression, respectively, and answered questions related to their change in depression, anxiety and suicidal thoughts during the pandemic. Association between the individual beliefs as well as a composite Conspiracy Theory Belief Score (CTBS) and mental health measures was analysed using linear regression models. Results: Overall, belief in conspiracy theories was relatively moderate in our sample. Sex and age appeared to have a significant effect on the Overall Conspiracy Theory Belief Score (CTBS), with women having a higher score and scores increasing with age. Some of the individual beliefs also showed associations with age and sex. State anxiety and depression was not significantly associated with CTBS, however in case of depression some individual items were, and symptom clusters within CES-D also showed a pattern of association with some of the individual items. As far as changes in mental health during the pandemic is concerned, no association between overall beliefs and changes in anxiety or depression was found. However, higher overall belief in conspiracy theories was associated with a decrease in suicidal thoughts. Discussion: In our study, we explored the association between conspiracy theories and mental well-being as well as its changes during the COVID-19 pandemic. We found a specific pattern of association between belief in distinct theories and some aspects of depression, as well as lower increase in suicidal ideation in association with increased belief in conspiracy theories. Understanding the role of belief in theories can be key to designing mental health interventions when reacting to unforeseen events in the future. (Neuropsychopharmacol Hung 2022; 24(1): 42-55).

Association between change in suicidal ideation, and distinct symptoms of depression and sleep changes during COVID-19.

COVID-19 has created a situation that has never been experienced before, challenging the mobilization of adaptive coping strategies. There has been a marked increase in suicides and suicidal ideation following the onset of COVID-19 likely reflecting the toll of the pandemic on mental health. The aim of our study to investigate the associations between depressive symptoms and distinct symptom clusters and lifestyle changes related to sleep, eating and physical activity and change in suicidal thoughts and thinking about death during the pandemic. Analyses involved data from the Hungarian part of the COMET-G (COVID-19 Mental health in Ternational for the General population) study, including 763 Hungarian adults, who completed a detailed questionnaire focusing on changes in behavior, lifestyle, activity and mental health during the pandemic. The dataset was analyzed using ordinal regression models adjusted for age and sex. Depression, as well as its symptom clusters, including anhedonia and depressed mood and somatic complaints had a significant, but small effect increasing suicidal ideation, while the effect of irritability and social relationship problems was more marked. In case of lifestyle factors no associations was found between change in eating habits or physical activity and change in suicidal ideations, however, sleeprelated changes were associated with a significant increase in suicidal thoughts during the pandemic. Our findings show that not all symptoms related to mood disturbance have an equally marked effect on suicidal ideating and thus suicide risk, emphasizing the role of detailed screening and evaluation even in subclinical populations in times of such crises, and also highlight the importance of considering sleep problems when evaluating suicide risk. Thus, our findings help identify relevant targets for screening and intervention in decreasing suicide risk during crises. (Neuropsychopharmacol Hung 2022; 24(3): 134-143).

Does TMS Influence Verbal Function and Treat the Language Decline in Schizophrenia? Finding Answers via Systematic Review of Current Research.

BACKGROUND: rTMS is an adequately safe intervention that is approved for treatment of various neuropsychiatric conditions. There is ongoing research on the application of rTMS for the treatment of resistant auditory verbal hallucinations (AVH) in schizophrenia (SZ), and also for alleviating negative and cognitive symptoms in patients with chronic SZ states. Language decline, as a part of thought, language and communication disorders, is one of the key symptoms of SZ, having a significant bearing on decreased social/interpersonal functioning of these patients. In this regard rTMS may be a promising treatment approach, while serving as an important research tool in the field of SZ studies. The aim of our present study was to compile and evaluate the existing data on whether rTMS affects verbal function in SZ patients, and if rTMS has any efficacy for the treatment of language disturbances in SZ spectrum disorders. SUBJECTS AND METHODS: Our systematic search over the PubMed database revealed a total of 200 articles, of which 21 met criteria for inclusion in this analysis. We have reviewed in detail the study designs, inclusion and exclusion criteria, rTMS protocols and cognitive (in particular, speech/language domain) assessments reported in these articles. RESULTS: The 21 studies focused on two key topic clusters: (i) low-frequency rTMS treatment of AVH in SZ, and (ii) high-frequency rTMS treatment of negative and cognitive SZ symptoms. The majority of study participants presented with chronic and treatment-resistant states. Most of the low-frequency rTMS studies did not show any difference in verbal test measures in SZ in response to treatment. Less than a half of high-frequency rTMS studies reported a delayed positive effect on language cognitive domains in SZ. There were sporadic reports on dropouts associated with a decline in scores for auditory verbal learning tests. CONCLUSIONS: Our systematic review found rTMS to be generally safe in relation to verbal/speech function, and suggested that verbal memory tests could serve as a measure of safety of this treatment procedure in SZ patients. Speech effects of rTMS have only been registered over long-term observation periods, such that time-frame which should be considered as an important factor for future studies. In our project "Innovative Neuropsychiatry Research Bank: Priority-2030" we plan to clarify (i) efficient rTMS protocols targeting neurocognitive improvement in SZ, and (ii) the cohort of SZ patients with a particular cognitive endophenotype and language profile amenable to treatment with rTMS, with a focus on language scores.

The Effects of Transcranial Magnetic Stimulation on Cognitive Functioning in Bipolar Depression: A Systematic Review.

BACKGROUND: The features of bipolar affective disorder (BAD) include mood swings, recurring episodes of mania, depression, and mixed states. Numerous studies of people living with BAD have found the presence of cognitive impairments that affect patients' daily social functioning and quality of life. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique recommended for the treatment of bipolar depression (BD). The effect of TMS on cognitive function in BD patients remains mostly unclear. SUBJECTS AND METHODS: We carried out a systematic search in the databases of PubMed and Scopus for the whole publication period until March 30th, 2022. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) was used to identify all data published in English language and related to the use of TMS in the treatment of depression in BAD and its impact on cognitive function. Articles related to TMS, cognition, and BD were identified using predefined term search algorithms. Articles on clinical trials and case reports were included, but reviews were excluded. The PICOS (Population Intervention Comparison Outputs Study) formula in our review included: P - patients with bipolar depression, I - TMS treatment, C - patients without TMS treatment / placebo TMS, O - changes in cognitive functions, S - all types of original studies. RESULTS: Within the primary screening for assessment of full texts, 25 documents met our selection criteria to test the effect of TMS on cognitive functioning in BD. Based on a secondary screening of the full-text analysis, 10 articles (N=259 patients) were included into the current review. Among these, the majority of articles were based on the randomized controlled trials (RCTs, N=6), whereas the remaining four presented a case report, an open unblinded study, an open-label study, and a pilot study, respectively. Most of the studies produced mixed result. However, the limited data strongly suggested that TMS is without detriment to cognition in BD patients and is indeed beneficial in specific domains of cognitive function, namely (i) verbal fluency, (ii) verbal memory, and (iii) executive functioning. Small sample sizes, heterogeneity across the study designs, lack of the control groups data in some of the trials, different TMS protocols parameters and outcome measures represent significant limitations for comparing and analyzing the available results. CONCLUSIONS: Thus, present data on the effects of TMS in improving cognition in BD patients remains limited. To our mind, in order to evaluate properly the effectiveness of TMS in cognitive functioning improvement in BD, there is need for further randomized controlled trials and the corresponding development of the clinical standards for research recommendations. Such studies could define the appropriate methods for valid assessments of cognitive functions, and guide the selection of optimal TMS protocols when planning RCTs. We suggest that efforts should be expended to organize centralized large-scale clinical trials to determine the optimal parameters of TMS procedures and the range of effects of this treatment on various indicators of cognitive functioning in BD. This applies equally to other socially significant mental disorders marked by perturbations in cognitive functioning.

Cryptogenic Stroke In The Context of Pandemic-Related Stress: The Role of Arterial Hemodynamics.

BACKGROUND: Up to 45% of ischemic strokes are cryptogenic, which is an impediment to proposing preventative measures. In this investigation we aimed to study underlying heart arrhythmias in patients with cryptogenic stroke, taking into consideration the context of the COVID-19 pandemic and stressful lockdown conditions. SUBJECTS AND METHODS: In this cross-sectional study we observed 52 patients with cryptogenic stroke >1 month after acute presentation, and a control group consisting of 88 patients without stroke. All patients undewent the laboratory and instrumental investigation consisting of the following: lipid spectrum; hemostasiograms; hemoglobin A1c; transthoracic or/and transesophageal echocardiography; 24-hours monitoring of ECG; computer tomography or magnetic resonance imaging of the brain. We studied the hemodynamics of the common carotid arteries using Doppler ultrasound imaging and digital sphygmography (SG). RESULTS: The groups were indentical with respect to the preponderance of study parameters (sex, age, comorbidities, instrumental and laboratory data). The ischemic stroke group had a statistically significant difference in the prevalence of the first type of extrasystolic arrhythmia according to our gradation of extrasystoles, which are ventricular systoles of extrasystolic contraction appearing before the transmitral blood flow peak (peak E in echocardiography). We observed that earlier ventricular systoles of extrasystole in the cardiac cycle predicted for greater growth of hemodynamic and kinetic parameters. Calculating the indices of a four-field table established the significant relationship between the moment of appearance of extrasystolic ventricular contraction in the cardiac cycle and the risk for cryptogenic stroke (normalized value of the Pearson coefficient (C`) of the two paramaters was 0.318). CONCLUSIONS: Extrasystolic arrhythmia appeared as an additional risk factor of earlier stroke. The most dangerous type of arrhythmia was when the ventricular contraction of the extrasystole appeared before the transmitral blood flow peak in the cardiac cycle. This observation could present a risk-marker for brain-related cardiovascular complications such as stroke, which might be patients suffering from different internal diseases, especially in the context of environmental stress conditions of the current pandemic and its related lockdown measures.

The Efficacy of Mobile Phone-Based Interventions for the Treatment of Depression: A Systematic Meta-Review of Meta-Analyses of Randomized Controlled Trials.

BACKGROUND: Depression is ranked by the World Health Organization as the single largest contributor to global disability. The shortage of health care resources, conditions of social distancing during the present pandemic, and the continuing need of patients with subclinical depression and in remission for supportive therapies, all together motivate a search for new approaches to deliver appropriate and timeous treatment for depression. SUBJECTS AND METHODS: We conducted a systematic literature search of meta-analyses and systematic reviews on the topic of mobile apps for the treatment of depression using the Medline (Pubmed) database during the period ending March 30th, 2022. This review was managed following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and entailed a search strategy using key-words related to depressive states and mobile phone apps for depression treatment and management. RESULTS: A total of 15 full-text articles met the inclusion criteria for the current systematic review. 13 of the 15 studies reported on the effectiveness of mobile apps for treating depression, finding a significant reduction in depressive symptoms with small-to-medium positive effect size. Patients with severe depression experienced greater benefits from a behavioral activation app, whereas those with mild depression responded better to a mindfulness app. The impact of clinicians' support is difficult to isolated completely from the particular interventions' effects. CONCLUSIONS: Mobile-based intervention apps present a convenient tool for prevention and supportive therapy of depression. The use of mobile apps may act as an efficient intervention to reduce depression in adult patients regardless the potential contributing factors of gender or co-morbidities, but the role of mobile apps should be contrasted with other digital interventions.

Non-Psychiatrist Healthcare Professionals? Attitudes Toward Patients with Mental Disorders: Lower Scores in Social Distance as a Fragile Facet of Public Stigma Against Depression.

BACKGROUND: The stigmatization by healthcare professionals (HP) of patients suffering from mental disorders is an important problem that interferes with the delivery of medical assistance. Social distancing by HP is an integral part of stigmatization, which differs between various mental disorders, as well as between psychiatrists (PSY) versus nonpsychiatrist healthcare professionals (NPHP). SUBJECTS AND METHODS: The study included 141 HP: PSY (n=20; 36.2±4.2 y.o.) and NPHP (n=121; 25.9±2.2 y.o.). The NPHP group included general practitioners (GP)/physicians (n=29; 20.6%), surgeons (n=19; 13.5%), obstetrician-gynecologists (n=26; 18.4%), neurologists (n=11; 7.8%), pediatricians (n=6; 4.3%), and other subspecialists (including urologists, tuberculosis specialists, ophthalmologists and dermatologists) (n=30; 21.3%). The modified Bogardus Social Distance Self-Assessment Scale (BSDS) was used to evaluate the indicators of social distance phenomena. The assessment was performed by HP for the following groups of patients with the following mental disorders: alcohol use disorder, bipolar disorder, depression, drug addiction, epilepsy, mental retardation, personality disorder, schizophrenia. All statistical calculations were performed using IBM SPSS-27 software (IBM Corp. 2021, licensed to Samara State Medical University). P-value ≤0.05 was determined as significant for the between-group (PSY vs NPHP) comparisons using a nonparametric Mann-Whitney U-test. RESULTS: Our data analysis showed that HP achieved varying social distance scores for patients depending on the type of mental disorder, but with common trends among PSY and NPHPs. The mean (SD) scores of social distance ranged from 3.65(1.50) for depression to 5.25 (1.74) for drug addiction in the PSY, versus 3.44 (1.69), 6.19 (1.37) in NPHP, respectively. As compared to PSY, mean BSDS total scores were greater in the NPHP group, notably in the obstetricians-gynecologist - 6.27(1.40), and GP - 6.62 (0.90) groups, with similar trends of differing attitudes appeared among pediatricians - 7.00 (0.01) - regarding drug addiction, whereas the neurologists demonstrated a tendency towards lower social distance in relation to patients with depression - 2.27 (1.68), and epilepsy - 2.82 (1.47). CONCLUSIONS: Social distance measures by PSY and NPHP groups in contemporary Russia were highest in relation to patients with drug addiction, and lowest scores for depression and epilepsy. Stigmatization among HPs seems to influence health care delivery to certain categories of patients, which calls for further investigation. Higher social distance scores for patients with drug addiction might be related to higher stigma and lack of compassion toward these patients. Conversely, lower scores of social distance and corresponding emotional acceptance of people with depression by HP might interfere in the timely diagnosis and availability of appropriate care at an early stage amenable to treatment. This might reflect the cultural context of depressive mentality in Russia, or elevated prevalence of depressive states among HP. We propose interventions aiming to destigmatize mental disorders by targeting particular subgroups of vulnerable patients and also certain representatives of HP community.

Pharmacogenetic Aspects of COVID-19 Management and Post-COVID-19 Depression Treatment with Fluvoxamine.

BACKGROUND: Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective reuptake inhibitor fluvoxamine has been considered as a prophylaxis against depression in early COVID-19 patients, with additional benefits apparently arising from its antiviral activity. In this narrative review, we draw attention to the body of evidence showing efficacy of fluvoxamine in protecting against depressive disorders in COVID-19 patients, while also attenuating the severity of COVID-19 disease, with a notable reduction in the need for intubation and lower mortality. We consider this potential two-fold action of fluvoxamine in the light of its pharmacogenetic and pharmacological profiles. SUBJECTS AND METHODS: Full-text publications in English and Russian in Google Scholar, PubMed, NCBI, Web of Science, and E-Library databases were selected by keywords, solitary and in combination (fluvoxamine, COVID-19, depression, anxiety, antidepressants, adverse reactions) for the period from March 01, 2020 to June 06, 2022. We also analyzed the full-text publications in English and Russian language reporting adverse reactions caused by fluvoxamine use for the period from 2012 to 2022. RESULTS: The literature search yielded 10 papers reporting on the efficacy fluvoxamine in relieving depressive symptoms in COVID-19 patients, and 3 papers on its effect on medical outcome. The preponderance of data indicated a dual therapeutic action of fluvoxamine, and our further literature investigation was informative about drug-drug interactions and genetic factors moderating the antidepressant efficacy of fluvoxamine. CONCLUSIONS: Patients with COVID-19 seeking psychopharmacological treatment for depressive symptoms must be informed of the benefits and risks of fluvoxamine use. Several lines of findings indicate this agent to possess an additional antiviral action. However, optimal dosage regimens and the trade-off with drug-drug interactions remain unclear. Pharmacogenetic testing may assist in evidence-based optimization of fluvoxamine dosages in the context of COVID-19 infection with comorbid depression.

Possible Clinical and Pharmacogenetic Predictors of the Efficacy and Safety of Carbamazepine in Post-COVID-19 Depression.

BACKGROUND: Individuals who have suffered from novel coronavirus disease (COVID-19) are at risk for developing post-COVID neuropsychiatric disorders, which are an integral part of the Long COVID syndrome. Depression and/or anxiety are considered the most common psychiatric disorders after experiencing COVID-19. Certain antiepileptic drugs, notably, carbamazepine (CMZ), are effective in the treatment of mood disorders, especially as mood stabilizers in bipolar affective disorder (BAD), but the efficacy of CMZ in Long COVID remains to be established. The aim of the review was to investigate pharmacogenetic predictors of safety and efficacy of CMZ in patients with depressive symptoms of Long COVID during the post-infection period. SUBJECTS AND METHODS: We carried out a systematic search for publications in English and Russian on the safety and efficacy of CMZ in depressive disorders of different etiologies in the PubMed, Web of Science, Springer, Clinical Keys, Google Schooler, E-Library databases using keywords and combined word searches (carbamazepine, COVID-19, depression, epilepsy, post-COVID-syndrome) for the period from January 01,2020 to June 10, 2022. RESULTS: We review the main adverse drug reactions (ADRs) associated with CMZ, drug-drug interactions, and genetic predictors of the development of ADR. Here, we consider as risk factors, candidate genes for CMZ metabolism, CMZ transport, immunohistocompatibility genes, and candidate genes for QT prolongation. CONCLUSIONS: The choice of antidepressant treatment for patients with Long COVID is fraught because of the frequent occurrence of subclinical (interictal) epileptiform activity in the EEG. Consequently, antidepressant medications with a proconvulsant effect are contraindicated for Long COVID patients. CMZ may be a promising alternative for the treatment of depressive disorders in Long COVID states, given its mood-stabilizer, antidepressant, and antiepileptic profile.