The Effectiveness of Virtual Reality-Based Training on Cognitive, Social, and Physical Functioning in High-Functioning Older Adults (CoSoPhy FX): 2-Arm, Parallel-Group Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) has emerged as a promising technology for enhancing the health care of older individuals, particularly in the domains of cognition, physical activity, and social engagement. However, existing VR products and services have limited availability and affordability; hence, there is a need for a scientifically validated and personalized VR service to be used by older adults in their homes, which can improve their overall physical, cognitive, and social well-being. OBJECTIVE: The main purpose of the CoSoPhy FX (Cognitive, Social, and Physical Effects) study was to analyze the effects of a VR-based digital therapeutics app on the cognitive, social, and physical performance abilities of healthy (high-functioning) older adults. This paper presents the study protocol and the results from the recruitment phase. METHODS: A group of 188 healthy older adults aged 65-85 years, recruited at the Medical University of Lodz, Poland, were randomly allocated to the experimental group (VR dual-task training program) or to the control group (using a VR headset app showing nature videos). A total of 3 cognitive exercises were performed in various 360° nature environments delivered via a VR head-mounted display; the participants listened to their preferred music genre. Each patient received 3 sessions of 12 minutes per week for 12 weeks, totaling a minimum of 36 sessions per participant. Attention and working memory (Central Nervous System Vital Signs computerized cognitive battery) were used as primary outcomes, while other cognitive domains in the Central Nervous System Vital Signs battery, quality of life (World Health Organization-5 Well-Being Index), health-related quality of life (EQ-5D-5L), and anxiety (General Anxiety Disorder 7-item questionnaire) were the secondary outcomes. The group-by-time interaction was determined using linear mixed models with participants' individual slopes. RESULTS: In total, 122 (39%) of the initial 310 participants failed to meet the inclusion criteria, resulting in a recruitment rate of 61% (188/310). Among the participants, 68 successfully completed the intervention and 62 completed the control treatment. The data are currently being analyzed, and we plan to publish the results by the end of September 2024. CONCLUSIONS: VR interventions have significant potential among healthy older individuals. VR can address various aspects of well-being by stimulating cognitive functions, promoting physical activity, and facilitating social interaction. However, challenges such as physical discomfort, technology acceptance, safety concerns, and cost must be considered when implementing them for older adults. Further research is needed to determine the long-term effects of VR-based interventions, optimal intervention designs, and the specific populations that would benefit most. TRIAL REGISTRATION: ClinicalTrials.gov NCT05369897; https://clinicaltrials.gov/study/NCT05369897. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53261.

Virtual reality-based training may improve visual memory and some aspects of sustained attention among healthy older adults - preliminary results of a randomized controlled study.

BACKGROUND/AIMS: Older age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults. METHODS: Seventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65-85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups. RESULTS: The users performed, on average, 39.8 sessions (range 1-100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants' sex, age, and years of education. The differences in CNS Vital Signs' global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant. CONCLUSIONS: VR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT05369897.

Expression of Dopamine D1-4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D1, D2, D3, D4 and serotonin 5-HT1A, 5-HT2A, and 5-HT3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects. Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D1-4 and serotonin 5-HT1A-3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC50, half of IC50, and one-quarter of IC50 concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D1, D2 and D4 receptors (p < 0.001), and significantly lower mRNA expression of 5-HT3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D1 lost its significance, while that of D3, 5-HT1A, 5-HT2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors. Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.

Fasting serum leptin levels in elderly women with major depressive disorder: a case-control study.

OBJECTIVE: Leptin is produced in the adipose tissue. It controls energy homeostasis by reducing food intake and increasing energy expenditure. According to the "leptin hypothesis of depression", chronic stress leads to reduced leptin concentration and leptin insufficiency may underlie depressive symptoms. However, it is also hypothesized that observed in depressed patients differences in leptin levels may be secondary to differences in adiposity. The aim of this case-control study is to evaluate fasting serum leptin levels in elderly women with major depression disorder and to compare them with non-depressed elderly women. METHODS: We measured fasting serum leptins levels and body composition in 32 elderly (age ≥60 years) European Caucasian women with major depression disorder and in 49 non-depressed elderly (age ≥ 60 years) European Caucasian women. RESULTS: There was no statistically significant difference (p=0.14) in fasting serum leptin level between patients with depression (3.04±1.79 ng/mL) and control subjects (2.46±1.70 ng/mL). CONCLUSIONS: In two groups of subjects with comparable adiposity parameters we did not confirm that leptin level is changed in patients with depression. We assume that changes in leptin level in patients with depression may be mediated by adiposity.

The second agent effect: Interpersonal predictive coding in people with schizophrenia.

Interpersonal predictive coding (IPC) enables one to use the information conveyed by the communicative action of one agent to predict the response of another agent. IPC relies both on explicit reflective processes (processing of communicative intentions) and automatic reflexive processes (motor resonance). Predictive coding deficits may underlie positive symptoms in people with schizophrenia (SCZ), yet IPC has not been analyzed in SCZ. Thirty-nine SCZ and 22 controls (HC) completed a simultaneous masking detection task, during which they observed either communicative (Com) or individual (Ind) actions of agent A and had to report the presence of the agent B, who was shown in half of the trials. In line with previous findings, detection criterion was lowered after Com as compared to Ind, suggesting a higher tendency to report the presence of a second agent after observing agent A's communicative gestures . Surprisingly, this effect was found to a similar extent in both groups. Communicative criterion was linked to mentalizing abilities, but not to symptoms in SCZ. Finding that SCZ show similar IPC as HC adds to the previous evidence that reflexive processes may be relatively intact in patients. Furthermore, the level of reflective processes may be crucial for patients' social functioning.

Red Blood Cells Parameters in Patients with Acute Schizophrenia, Unipolar Depression and Bipolar Disorder.

BACKGROUND: There are no studies comparing red blood cell parameters between patients with schizophrenia, bipolar disorder and unipolar depression. The aim of this study was to compare differences in erythrocyte parameters (red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)) in patients with schizophrenia (SHZ), unipolar depression (UD) and bipolar disorder (BIP): bipolar depression (BD) and mania (BM). SUBJECTS AND METHODS: This was a retrospective, cross-sectional, naturalistic study of 2381 patients (SHZ n=1244; UD n=794; BIP n=343, BD n=259, BM n=84). RESULTS: There was significant difference for all red cell parameters between study groups (p<0.001). Age and sex may affect various erythrocyte parameters. CONCLUSION: There are differences in erythrocyte parameters between schizophrenia, unipolar depression and bipolar disorder. Compared with schizophrenia, significantly higher percentage of patients with affective disorders has anemia or abnormal erythrocyte parameters. Positive correlations between age and MCV and RDW and negative correlation between other parameters and age were found in all study groups.

Biological motion sensitivity, but not interpersonal predictive coding is impaired in schizophrenia.

Social predictive coding is now a well-established phenomenon in healthy individuals. It has been demonstrated that the communicative gestures of one agent may be effectively used to predict the actions of other agents. Individuals with schizophrenia often present social-cognitive deficits. The aim of this paper is to examine interpersonal predictive coding in patients with schizophrenia. Forty-six participants with schizophrenia and 40 healthy controls (HC) completed a simultaneous masking detection task (Interpersonal Detection Task; IDT), during which they observed point-light displays of two agents (A and B). During the communicative condition, agent A performed a communicative gesture, to which agent B responded accordingly. During the individual condition, agent A performed a noncommunicative action instead of the communicative gesture. Upon completion of the IDT, participants were asked to explicitly classify the actions of two agents based on nonmasked videos of point-light dyads. In line with previous findings, people with schizophrenia presented a reduced masking threshold for biological motion displays, and were less able to correctly recognize the actions of two agents during the explicit recognition task. However, observing the communicative gesture of agent A enhanced the visual discrimination of agent B in participants from all groups. This effect was observed despite the fact that SCZ presented overall diminished sensitivity to biological motion during IDT. Interpersonal predictive coding, which at least partially relies upon implicit processes, may be less impaired in people with schizophrenia than explicit social-cognitive processes (e.g., theory of mind). (PsycINFO Database Record

Affective and Cognitive Verbal Theory of Mind in Schizophrenia: Results From a Novel Paradigm.

OBJECTIVES: Impairments of Theory of Mind (ToM) have been repeatedly demonstrated in patients with schizophrenia (SCZ). However, only a handful of studies have explored deficits in affective and cognitive subcomponents of ToM. Thus, this study aims to examine affective and cognitive ToM abilities in SCZ by using a novel, verbal paradigm. METHODS: Twenty-four SCZ and 22 healthy comparison subjects (HC) completed a battery of tasks, which consisted of: (i) Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), (ii) three well-established tasks measuring social cognitive abilities, and (iii) original tasks which assess ability to infer cognitive and affective mental states based on everyday verbal social interactions. RESULTS: In line with previous findings, SCZ were outperformed by HC in all tasks. However, the interaction effect of the group and the task showed that cognitive (as opposed to affective) ToM was more profoundly impaired in patients with SCZ. CONCLUSIONS: It is proposed that in SCZ group cognitive ToM is more impaired as it involves more effortful reflective processes, while affective ToM, which is more automatic and based on reflexive processes, may differentiate patients from healthy comparison subjects to a lesser extent. (JINS, 2018, 24, 305-309).

Body composition does not affect serum levels of cathelicidin LL-37 in elderly women with unipolar depression.

OBJECTIVES: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in elderly women with depression. The aim of this study is to evaluate serum LL-37 levels in elderly women with depression and to compare them with non-depressed elderly women, matched for anthropometric and body composition parameters. METHODS: Forty women with unipolar depression and 23 non-depressed women (age ≥60 years) were included into the study. Anthropometric measurements and biochemical analyzes were performed. Concentration of LL-37 in serum was assessed using ELISA method. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). RESULTS: There was a statistically significant difference (p =.038) in serum LL-37 level between patients with depression (3.55 ± 6.57 ng/mL) and control subjects (2.01 ± 3.88 ng/mL). Apart from visceral adipose tissue mass (%) in the depression group, we found no associations between serum LL-37 and analyzed anthropometric or body composition parameters. CONCLUSIONS: Results of this study indicate that with the exception of visceral adipose tissue, LL-37 serum levels are not affected by anthropometric or body composition parameters. The association between visceral adipose tissue and LL-37 may indicate that visceral fat could be responsible for the increased LL-37 production.

Social cognition in neuropsychiatric populations: a comparison of theory of mind in schizophrenia and mesial temporal lobe epilepsy.

Social cognition deficits are observed both in patients with schizophrenia (SCZ) and in patients with mesial temporal lobe epilepsy (MTLE). This may be due to dysfunction of the amygdala network, which is a common feature of both diseases. In this study, SCZ (n = 48) or MTLE (n = 31) and healthy controls (HC, n = 47) completed assessments of mentalising (Reading Mind in the Eyes Test, RMET) and basic cognitive processing, e.g., working memory, executive functions and psychomotor speed (Trail-Making Test B and Digit Symbol). SCZ were also assessed with the Positive And Negative Syndrome Scale (PANSS). We found that the RMET scores of the two clinical groups were similar (p > 0.05) and lower than in the HCs (SCZ: p < 0.05; MTLE: p < 0.001). In the next step, SCZ were split into two groups with respect to the level of symptoms. Analysis of the RMET scores revealed no differences between the HC (M = 25.7 ± 4.1) and POS-LO (M = 25.3 ± 4.8); both groups outperformed the POS-HI group (M = 21.3 ± 5.2) and the MTLE group (M = 20.8 ± 4.6). No differences were found for the median-split with regard to negative symptoms. In SCZ, the mind-reading deficit appears to be associated with the level of positive symptoms. Both POS-HI and MTLE patients present significant mentalising deficits compared to healthy controls.

Platelet parameters (PLT, MPV, P-LCR) in patients with schizophrenia, unipolar depression and bipolar disorder.

There are no studies comparing platelet parameters platelet parameters (platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR)) between patients with schizophrenia, bipolar disorder and unipolar depression. Therefore, the aim of this study was to determine and compare differences in PLT, MPV and P-LCR in patients with schizophrenia, unipolar depression and bipolar disorder. This was a retrospective, cross-sectional, naturalistic study of 2377 patients (schizophrenia n=1243; unipolar depression n=791; bipolar disorder n=343, including bipolar depression n=259 and mania n=84). There were significant differences for PLT, MPV and P-LCR values between study groups. A significant percentage of patients with bipolar disorder had abnormal (too low or too high) number of platelets. Negative correlation between PLT and age was found in all study groups and positive correlation between age and MPV and P-LCR was found in patients with schizophrenia.