Theta-burst rTMS in schizophrenia to ameliorate negative and cognitive symptoms: study protocol for a double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Treatment effects of conventional approaches with antipsychotics or psychosocial interventions are limited when it comes to reducing negative and cognitive symptoms in schizophrenia. While there is emerging clinical evidence that new, augmented protocols based on theta-burst stimulation can increase rTMS efficacy dramatically in depression, data on similar augmented therapies are limited in schizophrenia. The different patterns of network impairments in subjects may underlie that some but not all patients responded to given stimulation locations. METHODS: Therefore, we propose an augmented theta-burst stimulation protocol in schizophrenia by stimulating both locations connected to negative symptoms: (1) the left dorsolateral prefrontal cortex (DLPFC), and (2) the vermis of the cerebellum. Ninety subjects with schizophrenia presenting negative symptoms and aging between 18 and 55 years will be randomized to active and sham stimulation in a 1:1 ratio. The TBS parameters we adopted follow the standard TBS protocols, with 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 100% active motor threshold. We plan to deliver 1800 stimuli to the left DLPFC and 1800 stimuli to the vermis daily in two 9.5-min blocks for 4 weeks. The primary endpoint is the change in negative symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Secondary efficacy endpoints are changes in cognitive flexibility, executive functioning, short-term memory, social cognition, and facial emotion recognition. The difference between study groups will be analyzed by a linear mixed model analysis with the difference relative to baseline in efficacy variables as the dependent variable and treatment group, visit, and treatment-by-visit interaction as independent variables. The safety outcome is the number of serious adverse events. DISCUSSION: This is a double-blind, sham-controlled, randomized medical device study to assess the efficacy and safety of an augmented theta-burst rTMS treatment in schizophrenia. We hypothesize that social cognition and negative symptoms of patients on active therapy will improve significantly compared to patients on sham treatment. TRIAL REGISTRATION: The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT05100888. All items from the World Health Organization Trial Registration Data Set are registered. Initial release: 10/19/2021.

The complexity of theory of mind deficit in schizophrenia: A cross-sectional analysis of baseline data from a longitudinal schizophrenia study.

A large number of trials have supported the functional significance of Theory of Mind (ToM) impairment in schizophrenia. However, the nature and the extent of the impairment are still unclear. Reviews on the topic suggest that, in many cases, studies use only one tool to assess the levels of difficulty in the field, limiting the validity of the measurement to one aspect of ToM. On the other hand, the divergence of the used assessment tools makes it hard to compare the result of these studies. Thus, we decided to use additional assessment tools to evaluate the extent of ToM in order to describe several aspects of the phenomenon. A hierarchical cluster analysis of variables was used on a sample of 68 participants with schizophrenia or schizoaffective disorder, to determine the similarity between variances of the assessed ToM subcomponents. Further cross-sectional correlational analysis was then performed to investigate the association between the identified clusters and other used measures (e.g.: neurocognition). The statistical analysis supported a five-cluster model. Identified clusters illustrate the difference between Hypo and HyperToM as well as the degree of ToM task complexity, allowing for a more accurate description of the nature of ToM deficit in schizophrenia.

Potential Role of the Antidepressants Fluoxetine and Fluvoxamine in the Treatment of COVID-19.

Mapping non-canonical cellular pathways affected by approved medications can accelerate drug repurposing efforts, which are crucial in situations with a global impact such as the COVID-19 pandemic. Fluoxetine and fluvoxamine are well-established and widely-used antidepressive agents that act as serotonin reuptake inhibitors (SSRI-s). Interestingly, these drugs have been reported earlier to act as lysosomotropic agents, inhibitors of acid sphingomyelinase in the lysosomes, and as ligands of sigma-1 receptors, mechanisms that might be used to fight severe outcomes of COVID-19. In certain cases, these drugs were administered for selected COVID-19 patients because of their antidepressive effects, while in other cases, clinical studies were performed to assess the effect of these drugs on treating COVID-19 patients. Clinical studies produced promising data that encourage the further investigation of fluoxetine and fluvoxamine regarding their use in COVID-19. In this review, we summarize experimental data and the results of the performed clinical studies. We also provide an overview of previous knowledge on the tissue distribution of these drugs and by integrating this information with the published experimental results, we highlight the real opportunity of using these drugs in our fight against COVID-19.

[Become the expert and embrace a positive attitude: communication strategies for discussing long-acting injectable antipsychotic treatment with patients living with schizophrenia].

Patients with schizophrenia often experience relapses that negatively impact long-term outcomes. Continuous antipsychotic treatment can reduce relapse risk; however, this can be hindered by nonadherence resulting from the poor insight, which is often associated with schizophrenia. A strong patient-physician-carer alliance can improve patient insight, and adherence. Long-acting injectable antipsychotic treatment (LAT) provides continuous treatment; however, its acceptance by the patient is often compromised by a lack of physician-patient communication. The COMP approach (Connectedness, Openness, Motivation, Partnership) was developed to build effective communication and aid discussions around treatment. Insights on COMP fed into the development of COMPLETE - a tool for discussing LAT with eligible patients including the following components: 'Life goals', 'Establish connection between goals and therapy', 'Therapy introduction' and 'Encourage long-term motivation'. The overarching objective of COMPLETE is to improve long-term outcomes in patients with schizophrenia. This article discusses the development of COMPLETE and its potential use in the management of schizophrenia.

[Review of the psychiatric aspects of anti-NMDA (N-methyl-D-aspartic acid) receptor encephalitis, case report, and our plans for a future study]. / Anti-NMDA (N-metil-D-aszparaginsav) receptor enkefalitisz: irodalmi összefoglaló, esetismertetés és kutatási terv.

Anti-NMDAR (N-methyl-D-aspartic acid receptor) encephalitis, first described in 2007, is a rare, autoimmune limbic encephalitis. In half of the cases anti-NMDAR antibodies are paraneoplastic manifestations of an underlying tumor (mostly ovarian teratoma). In the early stage of the disease psychiatric symptoms are prominent, therefore 60-70% of the patients are first treated in a psychiatric department. In most of the cases, typical neurological symptoms appear later. Besides the clinical picture and typical symptoms, verifying presence of IgG antibodies in the serum or CSF is necessary to set up the diagnosis. Other diagnostic tools, including laboratory tests, MRI, lumbar puncture or EEG are neither specific, nor sensitive enough. Therapy is based on supportive care, plasma exchange and immune suppression, intensive care administration can be necessary. If there is an underlying tumor, tumor removal is the first-line treatment. The disease can cause fatal complications in the acute phase but with adequate therapy long-term prognosis is good, although rehabilitation can last for months. In the past few years besides the typical clinical picture and illness course an increasing number of case reports described no typical neurological symptoms, only psychiatric symptoms, including psychosis, disorganized behavior, and catatonic symptoms. Immune suppressive treatment was still effective in most of these cases. Such cases present a difficult diagnostic challenge. These patients may receive unnecessary antipsychotic treatment because of the suspected schizophrenia, although they often suffer from serious extrapyramidal side effects. A few years ago there was a hypothesis that a small part of the patients who are treated with therapy-resistant schizophrenia may suffer from anti-NMDAR encephalitis, so they require a different kind of medication. Evidence from the latest publications did not confirm this hypothesis, although the connection between anti-NMDAR antibodies and disorders with psychotic symptoms is still not clear. After reviewing the most important studies regarding the psychiatric aspects of anti-NMDAR encephalitis, we present a case report of a patient with a pure psychiatric manifestation of this disease. We conclude with a short outline of the design and plan of our future study.

[An attempt to identify 22q11.2 microdeletions in samples of the Hungarian schizophrenia DNA bank by multiplex ligation-based probe amplification (MLPA): literature review, methodology and results]. / 22q11.2 deléciók azonosítási kísérlete magyar szkizofrénia biobank mintákon multiplex ligációs alapú próba amplifikáció (MLPA) módszerrel: irodalmi összefoglalás, módszertani leírás és eredmények.

Schizophrenia is a severe debilitating psychiatric disorder, with a typical onset in adolescence or early adulthood. This condition is characterized by heterogeneous symptoms (hallucinations, delusions, disorganized behaviour, affective flattening, and social isolation) and a life-time prevalence of 0.5-1.2%. In spite of the efforts to uncover the etiology of the disorder, its pathogenesis and neurobiological background are poorly understood. Given the high heritability in schizophrenia, genetic research remains an important area of focus. Besides the common variations of low penetrance - single nucleotid polymorphisms (SNPs) -, rare variants, mainly copy number variations (CNVs) play a role in the genetic architecture of the disorder. The most frequent CNV associated with schizophrenia is the hemizygous deletion of the 22q11.2 region. According to previous research this genetic variant occurs in 1% of the patients and conversely, 25% of the carriers of the 22q11.2 microdeletion will develop schizophrenia. The 22q11.2 deletion syndrome (22Q11DS, velocardiofacial (VCFS) syndrome, DiGeorge-syndrome) is usually a childhood diagnosis. Its prevalence is 1:2000-4000 considering all births. Patients can demonstrate heart developmental disorders, craniofacial (elongated face, hypertelorism), immunological (thymus-hypoplasia), endocrinological (hypocalcaemia) abnormalities, and neurodevelopmental alterations, but only a proportion will have these abnormalities due to incomplete penetrance. The variable symptoms complicate the recognition of the syndrome in the day to day medical practice. 25% of the known 22Q11DS patients develop schizophrenia but the risk of neuropsychiatric problems, like autism, ADHD and childhood conduct disorder is also increased, while early onset Parkinson's disease in also more frequent in adults. The schizophrenia phenotype is not distinguishable at the moment in patients with or without the 22q11 deletion. But emerging evidence suggests that early onset Parkinson's disease is more frequent in 22Q11DS and the effects of clozapine treatment could be different in schizophrenia with 22Q11DS. The question arises what is the incidence rate of the 22q11.2 microdeletion among our Hungarian DNA samples with schizophrenia. To answer the question, we utilized a new method used in routine genetic diagnostics, multiplex ligation-based probe amplification (MLPA). Although we genotyped the DNA of 315 Hungarian schizophrenia patients, we found no 22Q11DS in this cohort. The findings are discussed in terms of basic research and their translation into everyday clinical practice.