Minimum spanning tree analysis of EEG resting-state functional networks in schizophrenia.

Schizophrenia is a serious and complex mental disease, known to be associated with various subtle structural and functional deviations in the brain. Recently, increased attention is given to the analysis of brain-wide, global mechanisms, strongly altering the communication of long-distance brain areas in schizophrenia. Data of 32 patients with schizophrenia and 28 matched healthy control subjects were analyzed. Two minutes long 64-channel EEG recordings were registered during resting, eyes closed condition. Average connectivity strength was estimated with Weighted Phase Lag Index (wPLI) in lower frequencies: delta and theta, and Amplitude Envelope Correlation with leakage correction (AEC-c) in higher frequencies: alpha, beta, lower gamma and higher gamma. To analyze functional network topology Minimum Spanning Tree (MST) algorithms were applied. Results show that patients have weaker functional connectivity in delta and alpha frequency bands. Concerning network differences, the result of lower diameter, higher leaf number, and also higher maximum degree and maximum betweenness centrality in patients suggest a star-like, and more random network topology in patients with schizophrenia. Our findings are in accordance with some previous findings based on resting-state EEG (and fMRI) data, suggesting that MST network structure in schizophrenia is biased towards a less optimal, more centralized organization.

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.

[What is adult ADHD after all?]

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset mental disorder, demonstrates genetical effects, and is characterized by attention deficit, hyperactivity, and impulsivity. While ADHD was previously only considered a childhood disorder, longitudinal studies over the past decades have proven that in a significant number of cases, the symptoms of the disorder can also be detected in adulthood, and therefore affects 2-4% of the adult population. In Hungary, adult ADHD programs started about 20 years ago and has been able to provide help to many adults living with ADHD. However, this form of care needs further development in many aspects and suffers from capacity deficits at the national level. On July 4-6, 2023 we organized a CME course on adult ADHD at the Department of Psychiatry and Psychotherapy Semmelweis University. The objective of this course was to deepen the knowledge of participants and alleviate care difficulties in the long term through the sharing of information and good practices. As part of this, a narrative review was written, which touches on the current issues of diagnosing and treating ADHD in adults.

A comparison of visual and acoustic mismatch negativity as potential biomarkers in schizophrenia.

Mismatch negativity (MMN) is an event-related potential (ERP) component generated when an unexpected deviant stimulus occurs in a pattern of standard stimuli. Several studies showed that the MMN response to both auditory and visual stimuli is attenuated in schizophrenia. While previous studies investigated auditory and visual MMN in different cohorts, here we examined the potential clinical utility of MMN responses to auditory and visual stimuli within the same group of patients. Altogether 39 patients with schizophrenia and 39 healthy controls matched in age, gender, and education were enrolled. We recorded EEG using 64 channels in eight experimental blocks where we presented auditory and visual stimulus sequences. Mismatch responses were obtained by subtracting responses to standard from the physically identical deviant stimuli. We found a significant MMN response to the acoustic stimuli in the control group, whereas no significant mismatch response was observed in the patient group. The group difference was significant for the acoustic stimuli. The 12 vane windmill pattern evoked a significant MMN response in the early time window in the control group but not in the patient group. The 6 vane windmill pattern evoked MMN only in the patient group. However, we found no significant difference between the groups. Furthermore, we found no correlation between the clinical variables and the MMN amplitudes. Our results suggest that predictive processes underlying mismatch generation in patients with schizophrenia may be more affected in the acoustic compared to the visual domain. Acoustic MMN tends to be a more promising biomarker in schizophrenia.

Interpersonal Distance Theory of Autism and Its Implication for Cognitive Assessment, Therapy, and Daily Life.

The interpersonal distance (IPD) theory provides a novel approach to studying autism spectrum disorder (ASD). In this article, we present recent findings on the neurobiological underpinnings of IPD regulation that are distinct in individuals with ASD. We also discuss the potential influence of environmental factors on IPD. We suggest that different IPD regulation may have implications for cognitive performance in experimental and diagnostic settings, may influence the effectiveness of training and therapy, and may play a role in the typical forms of social communication and leisure activities chosen by autistic individuals. We argue that reconsidering the results of ASD research through the lens of IPD would lead to a different interpretation of previous findings. Finally, we propose a methodological approach to study this phenomenon systematically.

Intact predictive processing in autistic adults: evidence from statistical learning.

Impairment in predictive processes gained a lot of attention in recent years as an explanation for autistic symptoms. However, empirical evidence does not always underpin this framework. Thus, it is unclear what aspects of predictive processing are affected in autism spectrum disorder. In this study, we tested autistic adults on a task in which participants acquire probability-based regularities (that is, a statistical learning task). Twenty neurotypical and 22 autistic adults learned a probabilistic, temporally distributed regularity for about 40 min. Using frequentist and Bayesian methods, we found that autistic adults performed comparably to neurotypical adults, and the dynamics of learning did not differ between groups either. Thus, our study provides evidence for intact statistical learning in autistic adults. Furthermore, we discuss potential ways this result can extend the scope of the predictive processing framework, noting that atypical processing might not always mean a deficit in performance.

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study.

BACKGROUND: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. OBJECTIVE: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. METHODS: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. RESULTS: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. CONCLUSIONS: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-021346.

Altered interpersonal distance regulation in autism spectrum disorder.

Interpersonal distance regulation is an essential element of social communication. Its impairment in autism spectrum disorder (ASD) is widely acknowledged among practitioners, but only a handful of studies reported empirical research in real-life settings, focusing mainly on children. Interpersonal distance in adults with ASD and related autonomic functions received less attention. Here, we measured interpersonal distance along with heart rate variability (HRV) in adults with ASD, and tested the modulatory effects of eye-contact and attribution. Twenty-two adults diagnosed with ASD and 21 matched neurotypical controls participated in our study from October 2019 to February 2020. Our experimental design combined the modified version of the stop distance paradigm with HRV measurement controlling for eye contact between the experimenter and the participant to measure interpersonal distance. Still, we did not detect significant modulatory effect of eye contact and attribution. Our results showed a greater preferred distance in ASD. Moreover, we found lower baseline HRV and reduced HRV reactivity in ASD; however, these autonomic measurements could not predict preferred interpersonal distance. Our study highlights the importance of interpersonal space regulation in ASD: it might be considered that people with ASD need individually variable, presumably greater interpersonal distance. In addition, regardless of the distance they may have reduced autonomic regulatory capacity in social situations. Our results could help shape future experiments with sophisticated designs to grasp the complexity and underlying factors of distance regulation in typical and atypical populations.

Stronger coupling of emotional instability with reward processing in borderline personality disorder is predicted by schema modes.

BACKGROUND: Mood instability and risk-taking are hallmarks of borderline personality disorder (BPD). Schema modes are combinations of self-reflective evaluations, negative emotional states, and destructive coping strategies common in BPD. When activated, they can push patients with BPD into emotional turmoil and a dissociative state of mind. Our knowledge of the underlying neurocognitive mechanisms driving these changes is incomplete. We hypothesized that in patients with BPD, affective instability is more influenced by reward expectation, outcomes, and reward prediction errors (RPEs) during risky decision-making than in healthy controls. Additionally, we expected that these alterations would be related to schema modes. METHODS: Thirty-two patients with BPD and thirty-one healthy controls were recruited. We used an established behavioral paradigm to measure mood fluctuations during risky decision-making. The impact of expectations and RPEs on momentary mood was quantified by a computational model, and its parameters were estimated with hierarchical Bayesian analysis. Model parameters were compared using High-Density Intervals. RESULTS: We found that model parameters capturing the influence of RPE and Certain Rewards on mood were significantly higher in patients with BPD than in controls. These model parameters correlated significantly with schema modes, but not with depression severity. CONCLUSIONS: BPD is coupled with altered associations between mood fluctuation and reward processing under uncertainty. Our findings seem to be BPD-specific, as they stand in contrast with the correlates of depressive symptoms. Future studies should establish the clinical utility of these alterations, such as predicting or assessing therapeutic response in BPD.

[What Connects Bayes's Rule to Mental Health?]

A branch of computational psychiatry aims to handle the problems which arose due to the heterogeneity and comorbidity of mental illnesses by capturing phenotypic differences behind symptoms. In order to more accurately describe the mechanisms of the mind and its disturbances, it uses the tools and methods of computational cognitive science. In this paper, we introduce the reader to the (mathematical) language in which (Bayesian) predictive coding was written, which holds one of the possible explanations of the perceptual differences found on the autism or the psychosis spectrum. By representing prior knowledge and sampled sensory information as (prior and likelihood, respectively) distributions, the Bayes-rule allows us to calculate the inferred posterior distribution. The aforementioned terms are introduced through simple examples, such as coin tosses (inferring how biased it is) or making a diagnosis, however, this framework might also help us understand the more complex mechanisms of the mind. Studies show that visual perception can be examined following Bayesian formalization. The likelihood information can be manipulated with bistable or noisy stimuli, whereas through instructions and/or cues, prior expectations are formed. With the use of perceptual and response models fitted to cognitive task performance, it becomes possible to identify parameters which shed light on the features of information processing that characterize the perceptual alterations in certain clinical populations. At the end of the paper we draw attention to the limitations of computational modelling.

Intact fluency in autism? A comprehensive approach of verbal fluency task including word imageability and concreteness.

Verbal fluency is a cognitive function reflecting executive functions and the ability to retrieve the appropriate information from memory quickly. Previous studies reported conflicting results-impaired and intact verbal fluency-in autism spectrum disorder (ASD). Most studies concentrate on overall word productivity, errors, perseverations, clustering, or switching. We used a comprehensive approach to evaluate the reported discrepancy in the literature and introduced a new angle using the concept of word abstraction and imageability. Moreover, we analyzed the performance in two-time intervals (0-30 s and 31-60 s) to assess the temporal dynamics of verbal fluency and a possible activation or initiation deficit in autism. Sixteen adults with ASD and 16 neurotypical control participants, matched by gender, age, and education level, participated in our study. Contrary to our expectations, we did not find a significant difference between groups in word productivity, the number of errors, clustering, or temporal dynamics, neither in semantic nor in phonemic fluency tasks. Surprisingly, the two study groups' performance did not differ in terms of imageability or concreteness characteristics either. Our results raise the possibility that verbal fluency performance is intact in autism. We also suggest using a comprehensive approach when measuring fluency in autism. LAY SUMMARY: People with autism tend to think and communicate differently. In our study, we tested whether people with autism come up with more concrete or imageable words and whether their performance is better compared with neurotypicals in the beginning or in the later phase of a task measuring how many words they can produce in a minute. We did not detect any difference between the two groups; however, we recommend studying verbal fluency in autism from more and different angles in the future.

Cross-modal auditory priors drive the perception of bistable visual stimuli with reliable differences between individuals.

It is a widely held assumption that the brain performs perceptual inference by combining sensory information with prior expectations, weighted by their uncertainty. A distinction can be made between higher- and lower-level priors, which can be manipulated with associative learning and sensory priming, respectively. Here, we simultaneously investigate priming and the differential effect of auditory vs. visual associative cues on visual perception, and we also examine the reliability of individual differences. Healthy individuals (N = 29) performed a perceptual inference task twice with a one-week delay. They reported the perceived direction of motion of dot pairs, which were preceded by a probabilistic visuo-acoustic cue. In 30% of the trials, motion direction was ambiguous, and in half of these trials, the auditory versus the visual cue predicted opposing directions. Cue-stimulus contingency could change every 40 trials. On ambiguous trials where the visual and the auditory cue predicted conflicting directions of motion, participants made more decisions consistent with the prediction of the acoustic cue. Increased predictive processing under stimulus uncertainty was indicated by slower responses to ambiguous (vs. non-ambiguous) stimuli. Furthermore, priming effects were also observed in that perception of ambiguous stimuli was influenced by perceptual decisions on the previous ambiguous and unambiguous trials as well. Critically, behavioural effects had substantial inter-individual variability which showed high test-retest reliability (intraclass correlation coefficient (ICC) > 0.78). Overall, higher-level priors based on auditory (vs. visual) information had greater influence on visual perception, and lower-level priors were also in action. Importantly, we observed large and stable differences in various aspects of task performance. Computational modelling combined with neuroimaging could allow testing hypotheses regarding the potential mechanisms causing these behavioral effects. The reliability of the behavioural differences implicates that such perceptual inference tasks could be valuable tools during large-scale biomarker and neuroimaging studies.

Separating scale-free and oscillatory components of neural activity in schizophrenia.

INTRODUCTION: Alterations in narrow-band spectral power of electroencephalography (EEG) recordings are commonly reported in patients with schizophrenia (SZ). It is well established however that electrophysiological signals comprise a broadband scale-free (or fractal) component generated by mechanisms different from those producing oscillatory neural activity. Despite this known feature, it has not yet been investigated if spectral abnormalities found in SZ could be attributed to scale-free or oscillatory brain function. METHODS: In this study, we analyzed resting-state EEG recordings of 14 SZ patients and 14 healthy controls. Scale-free and oscillatory components of the power spectral density (PSD) were separated, and band-limited power (BLP) of the original (mixed) PSD, as well as its fractal and oscillatory components, was estimated in five frequency bands. The scaling property of the fractal component was characterized by its spectral exponent in two distinct frequency ranges (1-13 and 13-30 Hz). RESULTS: Analysis of the mixed PSD revealed a decrease of BLP in the delta band in SZ over the central regions; however, this difference could be attributed almost exclusively to a shift of power toward higher frequencies in the fractal component. Broadband neural activity expressed a true bimodal nature in all except frontal regions. Furthermore, both low- and high-range spectral exponents exhibited a characteristic topology over the cortex in both groups. CONCLUSION: Our results imply strong functional significance of scale-free neural activity in SZ and suggest that abnormalities in PSD may emerge from alterations of the fractal and not only the oscillatory components of neural activity.

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

Fronto-thalamic structural and effective connectivity and delusions in schizophrenia: a combined DTI/DCM study.

BACKGROUND: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network. METHODS: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). RESULTS: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. CONCLUSIONS: We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

A Method to Compare the Delivery of Psychiatric Care for People with Treatment-Resistant Schizophrenia.

INTRODUCTION: Community services are gaining ground when it comes to attention to patients with psychiatric diseases. Regarding patients with treatment-resistant schizophrenia (TRS), the use of information and communication technology (ICT) could help to shift the focus from hospital-centered attention to community services. This study compares the differences in mental health services provided for patients with TRS in Budapest (Hungary), Tel-Aviv (Israel) and Catalonia (Spain) by means of a method for the quick appraisal of gaps among the three places, for a potential implementation of the same ICT tool in these regions. METHODS: An adapted version of the Description and Standardised Evaluation of Services and Directories in Europe for Long Term Care (DESDE-LTC) instrument was made by researchers in Semmelweis University (Budapest, Hungary), Gertner Institute (Tel-Aviv, Israel) and Hospital de la Santa Creu I Sant Pau and Parc Sanitari Sant Joan de Déu (Catalonia, Spain). RESULTS: Two types of outpatient care services were available in the three regions. Only one type of day-care facility was common in the whole study area. Two residential care services, one for acute and the other for non-acute patients were available in every region. Finally, two self-care and volunteer-care facilities were available in the three places. CONCLUSION: Although the availability of services was different in each region, most of the services provided were sufficiently similar to allow the implementation of the same ICT solution in the three places.

[Possibilities of cognitive behavioral therapy in the oncological care]. / A kognitív viselkedésterápia lehetoségei az onkológiai ellátásban.

Cancer is a huge psychological difficulty both for the patient and the caregivers. Patients often suffer from hopelessness, helplessness, depression, anxiety or other psychological disturbances. Although the cognitive behavioral interventions (cognitive behavioral therapy, mindfulness) are evidence based, short, time-limited, focused treatments for patients with cancer, in Hungary there are only little evidence and experiences about application of cognitive behavioral methods in the oncological care. The main goal of this review to provide a survey about the cognitive behavioral theories and the international practical experiences in the field of oncological care, furthermore, to propose to apply these structured, directive, problem-focused interventions among patients with cancer to professionals which are able to decrease distress of patients or caregivers and these methods are able to treat the mental disorders, such as anxiety, depression, PTSD, which usually relate with cancer.

Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration.

PURPOSE: Pituitary adenylate Cyclase-Activating Polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAP-deficient (PACAP KO) mice provide evidence that endogenous PACAP has a neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation. The aim of the present study was to investigate the protective effects of endogenous PACAP in retinal inflammation. METHODS: Endotoxin-induced eye inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in PACAP KO and wild-type (Wt) mice. After LPS treatment, retinas were processed for histological examination. To detect the alterations of different proteins and cytokines, immunohistochemical, western blot and cytokine array were used. We also performed dark-adapted electroretinography (ERG) to detect the functional differences. RESULTS: The thickness of nearly all layers was significantly less in LPS-injected PACAP KO mice compared to Wt animals. Increased expression of Glial Fibrillary Acidic Protein (GFAP) was induced in Müller glial cells after LPS treatment, which was more intense in PACAP KO mice. The levels of pAkt and pGSK were decreased in PACAP KO group during inflammation. LPS treatment significantly increased cytokines (sICAM-1, JE, TIMP-1) in both treated groups, but it was more expressed in PACAP KO animals. Furthermore, ERG responses were disturbed after LPS injection in PACAP KO mice. CONCLUSION: Our results showed that endogenous PACAP has a protective role in LPS-caused retinal inflammation.

Mobile therapeutic attention for treatment-resistant schizophrenia (m-RESIST): a prospective multicentre feasibility study protocol in patients and their caregivers.

INTRODUCTION: Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. In the European Union, approximately 40% of people with schizophrenia have TRS. Factors such as the persistence of positive symptoms or higher risk of comorbidities leave clinicians with a complex scenario when treating these patients. Intervention strategies based on mHealth have demonstrated their ability to support and promote self-management-based strategies. Mobile therapeutic attention for treatment-resistant schizophrenia (m-RESIST), an innovative mHealth solution based on novel technology and offering high modular and flexible functioning, has been developed specifically for patients with TRS and their caregivers. As intervention in TRS is a challenge, it is necessary to perform a feasibility study before the cost-effectiveness testing stage. METHODS AND ANALYSIS: This manuscript describes the protocol for a prospective multicentre feasibility study in 45 patients with TRS and their caregivers who will be attended in the public health system of three localities: Hospital Santa Creu Sant Pau (Spain), Semmelweis University (Hungary) and Gertner Institute & Sheba Medical Center (Israel). The primary aim is to investigate the feasibility and acceptability of the m-RESIST solution, configured by three mHealth tools: an app, wearable and a web-based platform. The solution collects data about acceptability, usability and satisfaction, together with preliminary data on perceived quality of life, symptoms and economic variables. The secondary aim is to collect preliminary data on perceived quality of life, symptoms and economic variables. ETHICS AND DISSEMINATION: This study protocol, funded by the Horizon 2020 Programme of the European Union, has the approval of the ethics committees of the participating institutions. Participants will be fully informed of the purpose and procedures of the study, and signed inform consents will be obtained. The results will be published in peer-reviewed journals and presented in scientific conferences to ensure widespread dissemination. TRIAL REGISTRATION NUMBER: NCT03064776; Pre-results.

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

BACKGROUND: Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. METHODS: Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. RESULTS: A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.