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Schizophrenia spectrum disorder poses a complex challenge in psychiatric treatment due to its multifaceted symptomatology. Modified AVATAR therapy, an innovative virtual reality-based intervention integrating Cognitive Behavioral Therapy (CBT) techniques such as systematic desensitization, and Acceptance and Commitment Therapy (ACT) approach offers a promising avenue for addressing auditory verbal hallucinations (AVH). This case series report investigates the acceptability and feasibility of a modified AVATAR therapy in three patients diagnosed with schizophrenia spectrum disorder who experience distressing AVH. The study provides detailed demographic and clinical information, outlines the modified AVATAR therapy protocol, and presents outcomes measured through standardized assessments.The findings indicate a decrease in the severity of AVHs, along with enhancements in overall symptomatology after modified AVATAR therapy sessions. Moreover, qualitative perspectives from patients shed light on their favorable experiences and perceptions of this adapted intervention. Nonetheless, the results exhibited inconsistency across individual cases, underscoring challenges for future research and clinical applications in this domain. Nevertheless, in light of the hurdles accompanying the rehabilitation of schizophrenia patients, along with the evaluation and subsequent measurement of parameters affecting efficacy, modified AVATAR therapy could present a valuable addition to schizophrenia patient care.

Abstract 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.

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.