Low Functional network integrity in cognitively unimpaired and MCI subjects with depressive symptoms: results from a multi-center fMRI study.

Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salience Network, and the Cognitive Control Network. All 183 elderly subjects underwent a comprehensive neuropsychological evaluation and a 3 Tesla brain MRI scan. To assess the potential presence of depressive symptoms, the 13-item version of the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) was utilized. Participants were assigned into three groups based on their cognitive status: amnestic mild cognitive impairment (MCI), non-amnestic MCI, and healthy controls. Regarding affective symptoms, subjects were categorized into depressed and non-depressed groups. An increased mean eccentricity and network diameter were found in patients with depressive symptoms relative to non-depressed ones, and both measures showed correlations with depressive symptom severity. In patients with depressive symptoms, a functional hypoconnectivity was detected between the Anterior Cingulate Cortex (ACC) and the right amygdala in the FLN, which impairment correlated with depressive symptom severity. While no structural difference was found in subjects with depressive symptoms, the volume of the hippocampus and the thickness of the precuneus and the entorhinal cortex were decreased in subjects with MCI, especially in amnestic MCI. The increase in eccentricity and diameter indicates a more path-like functional network configuration that may lead to an impaired functional integration in depression, a possible cause of depressive symptomatology in the elderly.

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.

Virtual reality-based theory of mind intervention in schizophrenia: Preliminary efficacy results.

BACKGROUND: In recent years, a growing body of literature has supported the core nature and functional significance of Theory of Mind (ToM) deficit in schizophrenia. These findings have made ToM impairment a promising treatment target. However, despite the encouraging results, its complexity makes it difficult to develop new interventions and even to understand the exact nature and scope of the deficit. Yet, further investigation has suggested that using modern technology and multilevel assessment may help solve the problem. METHODS: Virtual Reality-based Theory of Mind Intervention (VR-ToMIS) is a recently developed structured method using the combination of cognitive and behavioral therapeutic techniques and the advantages of Virtual Reality (VR) technology. A controlled study with a three-month follow-up was conducted with 42 patients (suffering from schizophrenia or schizo-affective disorder) randomly assigned to either an experimental (VR-ToMIS) or control group (passive-VR). Repeated two-way factorial analysis of covariance was used to evaluate the effects of VR-ToMIS on symptoms, neuro- and social cognition, pragmatic skills, and quality of life when the effect of IQ was controlled. RESULTS: Patients participating in VR-ToMIS showed significant improvements in all types of ToM tasks (except for hyper-ToM task, based on the results of Cartoon test, Faux pas test and and Baron-Cohen Minds in the Eyes Test) compared to the control group with moderate to large effect sizes. In the case of negative and cognitive symptoms, significant between-group differences were also supported. Improvement was moderated by IQ in the case of higher-order ToM, manner, and relevance implicatures. Results were proved to be sustainable three months after the treatment. CONCLUSION: Although the presented results are considered preliminary, they support the potential of the integration of modern technology and traditional methods for future interventions.

Efficacy of metacognitive training on symptom severity, neurocognition and social cognition in patients with schizophrenia: A single-blind randomized controlled trial.

Over the past decades, a number of complementary treatments for schizophrenia have emerged. One of these is metacognitive training (MCT), which combines the principles of cognitive-behavioral therapies, cognitive remediation, and psychoeducation into a hybrid approach placing emphasis on increasing metacognitive awareness. The aim of our study was to investigate the efficacy of MCT on symptom severity, and neurocognitive and social cognitive functioning in schizophrenia; also, attention was paid to the assessment of subjective acceptability. Forty-six patients diagnosed with schizophrenia were included in our single-blind randomized controlled trial, who were assigned to the intervention or control group. The intervention group was provided standard MCT, while the control group received treatment as usual. We assessed symptom severity and cognitive functions before and after the training, as well as after a 6-month follow-up period. Compared to the control group, the intervention group showed improvement in overall symptom severity, and positive and disorganized symptoms. Training participans showed further improvement at the follow-up assessment. Regarding neurocognitive functions, improvement in visuospatial functions was observed between pre- and post-intervention assessments compared to the control group. Patients showed excellent adherence, and evaluated the training as useful and interesting. In line with the results of previous studies, our results demonstrate the efficacy of MCT on symptom severity in schizophrenia. Improvements in cognitive functions that are closely related to the onset and prevalence of symptoms of schizophrenia were also found.

[What makes someone a troll? The psychology of trolling: Systematic literature review].

BACKGROUND: The World Wide Web along with online social media has significantly changed the dynamics of communication. Information is easier and faster to access, but at the same time the relevance of the content often remains questionable, often confronting users with half-truths and untruths. Information consumption patterns have also changed a lot, allowing more room for the emergence of deviant, provocative behaviors through anonymity. The latter form of behavior can have different effects depending on its intensity and content, including, the polarization of opinions or the negative influence on users 'psychological wellbeing'. In our current article the literature on the pheno menon known as trolling in Internet slang was reviewed in order to better understand its nature and its possible effects. METHOD: Our systematic literature review was based on a computer search of the PubMed and ScienceDirect databases framed by the PRISMA guideline. The following keywords were used: "Internet" OR "Facebook" OR "Twitter" OR "Instagram" AND "troll" OR "trolling". RESULT: Based on the mentioned methon, a total number of 4575 articles were identified. Based on the inclusion and exclusion criteria 24 articles were included in the final sample. The results and experiences of the published papers were presented according to the subgroups formed on the basis of the purpose of the studies. CONCLUSION: Included articles focused primarily on understanding the motivation of trolling behavior and their impact on online behavior. However, the possible impact of trolls on individuals was left out of focus, leaving many open questions behind.

Regrouping scalets: Psychometric properties of the theory of mind picture stories task in a schizophrenic sample.

Theory of mind is one of the most intensively studied phenomena in the development of schizophrenic symptoms and impairments in social adjustment. Complex theory of mind processing requires both visual and verbal aspects of the social-perceptual and social-cognitive components of mind reading. Reliable assessment methods are considered essential for the proper conduct of research. The current study aims at investigating the psychometric properties of the Theory of Mind Picture Stories Task (ToM PST). Forty-seven patients with schizophrenia were enrolled in the study from three sites. Data from ToM PST were used for computing the consistency, reliability, and internal and construct validity of the test.Our preliminary findings showed less appropriate consistency. Therefore, we attempted to carry out structural changes on the task while preserving its scales and subscales, which measure crucial factors of ToM. The newly structured task has four scales. They show proper consistency (Sequencing: Cronbach's α = 0.70, Theory of a Single Person's Mind: α = 0.74, Switching Between Minds: α = 0.70, Comprehension of Misleading Behaviour: α = 0.67, Total: α = 0.80) with appropriate internal and construct validity, a moderate test-retest reliability over a four-month-course, and a proper inter-rater reliability.

[Virtual Reality in psychiatry and psychotherapy].

The use of virtual reality (VR) technology in psychiatry and psychotherapy has spread continiously over the last two decades. Researches has mainly focused on the VR-based therapy of anxiety disorders, but encouraging results have also been published in the field of diagnosis and therapy of eating disorders, addictions, autism, and ADHD. There have been fewer reports on the therapy of schizophrenia yet. In these cases VR interventions cover a wide range of symptoms. VR based interventions have already been developed for cognitive and social abilities that are more difficult to alleviate by medication. Among positive symptoms, the developed methods mainly focus on auditory hallucinations and delusions. In general, the current results confirm the effectiveness of VR-based therapeutic interventions and justify the need for further research. Research and therapy on this fieed at the VR Laboratory of the Department of Psychi - atry and Psychotherapy, Semmelweis University also support literature data. However, the widespread use of VRbased interventions requires further well-designed, blinded, randomized, long-term follow-up studies.

Case Report: Feasibility of a Novel Virtual Reality-Based Intervention for Patients With Schizophrenia.

Schizophrenia is a severe and disabling mental illness, associated with persistent difficulties in social functioning. While gaining and retaining a job or staying socially integrated can be very difficult for the patients, the treatment of poor functionality remains challenging with limited options in pharmacotherapy. To address the limitations of medical treatment, several interesting and innovative approaches have been introduced in the field of psychotherapy. Recent approaches incorporate modern technology as well, such as virtual reality. A potential therapeutic benefit of virtual reality is particularly significant when an interpersonal dimension of the problem needs to be addressed. One example is a Virtual Reality based Theory of Mind Intervention (VR-ToMIS), a novel method, which enables patients to practice complex social interactions without the burden of real-life consequences. Our paper presents a case report showing promising results of VR-ToMIS. Ms. Smith is a 50- year-old patient who has been suffering from schizophrenia for 20 years. Although in her case there was no problem with compliance throughout the years, she had severe problems regarding social functionality. With VR-ToMIS, she improved in ToM and communicative-pragmatic skills. The effects of the intervention went beyond the increased scores of the tests. Before the intervention there was a risk of the patient becoming unemployed as she was unable to follow the main principles of communicative exchange. Usually, her contribution was more informative than was required. After the intervention her communication became more balanced and she could retain her job. This case suggests that VR-ToMIS may be a promising tool for treating social disfunction in schizophrenia.

A novel virtual reality-based theory of mind intervention for outpatients with schizophrenia: A proof-of-concept pilot study.

Schizophrenia is a severe and highly disabling mental illness. Although several pharmacological solutions are available to alleviate symptoms of schizophrenia, they do not seem to provide solution for accompanying social dysfunctions. To handle this unmet clinical need, many innovative interventions have been developed recently. Considering the promising results on this field and the development trend, characterized by the growing proportion of included interactive technology, our research team developed a novel virtual reality (VR)-based targeted theory of mind (ToM) intervention (VR-ToMIS) for stable outpatients with schizophrenia. VR-ToMIS is a nine-session long structured and individualized method that uses cognitive and behavioural therapeutic techniques in an immersive VR environment. Our study was a randomized, controlled pilot study. Twenty-one patients have been recruited and randomly allocated to either VR-ToMIS or passive VR condition. Patients assigned to passive VR condition could use the same VR software as the VR-ToMIS group, but without any interventions. Effects on psychiatric symptoms, neurocognitive and social cognitive functions, pragmatic language skills and quality of life were evaluated by using analysis of covariance. According to our results, VR-ToMIS was associated with improvements in negative symptoms, in one neurocognitive field (immediate memory), ToM and pragmatic language skills, but no significant change in quality of life scores was detected. Significant changes in VR-ToMIS group were associated with moderate to large therapeutic effects (ηp 2  = .24-.46, φ = .55-.67). On the background of the presented pilot results, VR-ToMIS is concluded to be feasible and tolerable.

[The concept and characteristics of metacognition and its role in schizophrenia].

Schizophrenia research in the last decades led to rapid development of our knowledge regarding the cogni - tive deficits in the disease. Presence of neurocognitive and social cognitive deficits in schizophrenia is widely confirmed by empirical studies. Metacognition is one of the most recent and relatively less studied field of schizophrenia. Our lite rature review aims to introduce the concept and characteristics of metacognition. Then we overview the relation - ship between schizophrenia associated neurocognitive and social cognitive impairments and metacognitive deficits. Associations between the metacognitive deficits and the symptomatology will also be discussed. Finally, a method for the treatment of metacognitive deficits in schizophrenia will be suggested. The results of the overviewed studies sup - port, that the umbrella term of metacognition encompassing the neurocognitive and social cognitive deficits, may provide a comprehensive model to better understand how cognitive deficits contribute to the development and main - tanance of symptoms, and schizophrenia-associated serious social dysfunctions.

[Treatment of Theory of Mind deficits in schizophrenia by using Virtual Reality, the VR-ToMIS training (Virtual Reality based Theory of Mind Intervention in Schizophrenia)].

Rapid development in information technology has been observed recently and has led to valuable developments also in healthcare. 3D-bio-printing or the virtual simulations that help the acquisition of anatomical and pathological knowledge and testing the acquired knowledge are just some of the examples. This progress can be recognized also in psychiatry. One of the most spectacular ways of using these technologies in psychiatry might be the therapeutic techniques associated with Virtual Reality (VR) simulations, which are currently available for anxiety disorders, eating disorders and addictions. A research team of the Psychiatric and Psychotherapeutic Department of the Semmelweis University has developed a Virtual Reality-based intervention that fits in with this perspective. The intervention mainly aims at Theory of Mind deficit and pragmatic language impairment in schizophrenia. In this article the current status of our research team's work will be presented. The article reviews the literature that provides the basis for the development, leads the reader through the main stages of the development process, and finally the program itself will be introduced. Process and mechanism of change associated with the intervention and the potential risks of the use of VR will also be discussed.

Interventions for the treatment of theory of mind deficits in schizophrenia: Systematic literature review.

Theory of Mind (ToM) plays a central role in regulating social interactions and its impairment is consistently reported in schizophrenia. Regarding schizophrenia, ToM is usually discussed as a sub-domain of social cognition. Since social cognitive deficits have drawn the attention of researchers, a variety of novel treatment techniques and approaches targeting social cognitive deficits have been developed. Encouraging results have repeatedly been reported on the modifiability of social cognitive impairment through these techniques. However, emotional perception seems to be over-represented in these approaches at the expense of other areas, such as ToM. This article presents a systematic review on the social cognitive interventions of the last 10 years, which focused on the remediation of ToM or used techniques primarily focusing on one or more social cognitive domains other than ToM, but with hypothetical effects on it. The aim of our systematic review was to compare these intervention techniques in order to see how effective they are in the remediation of ToM, and to find the best techniques to ameliorate ToM deficits in schizophrenia. According to our findings targeted ToM intervention produced more improvement in ToM tasks, while data regarding non-ToM interventions showed contradictory results with limited effects on ToM.

[Treatment of metacognitive impairments in schizophrenia - The Metacognitive Training].

In the recent years plenty of therapeutic treatment methods have been developed, aimed at neurocognitive impairments in schizophrenia. These trainingprograms can hold up promising results in the improvement of neurocognitive functions. Nevertheless the generalisation on the daily life is not perspicuous. A reason for it might be the supposition, that further factors such as metacognition and social cognition may play a mediator role between neurocognition and functional outcomes. As a result, many socialcognitive remediation methods and programs have emerged targeting the impairment of deficits both in the field of neuro- and social cognition and deficits of metacognition. We review the specific impairments in schizophrenia (e.g. deficits of Theory of Mind, disorder of emotional perception, specific cognitive biases or impairment of metamemory), the construction and speciality of the Metacognitive Training, and the findings of studies aimed at the efficacy of the method. In addition to the socialcognitive remediation, the goal of Metacognitive Training is the correction of the cognitive biases playing an important role in the emergence and subsistence of delusions.