Anticholinergic load: A commonly neglected and preventable risk to cognition during schizophrenia treatment?

Background: Cognitive impairment is a widespread feature of schizophrenia, affecting nearly 80 % of patients. Prior research has linked the anticholinergic burden of psychiatric medications to these cognitive deficits. However, the impact of the anticholinergic burden from medications for physical morbidity remains underexplored. This study aimed to evaluate the anticholinergic burden of psychiatric and physical medications in patients with schizophrenia and assess its impact on cognitive function. Methods: A total of 178 patients with schizophrenia were recruited. The assessments included an ad hoc questionnaire for collecting demographic and clinical data. Anticholinergic burden was evaluated using the cumulative Drug Burden Index (cDBI) for each participant, and cognitive function was assessed using MATRICS. Psychopathology was measured using the PANSS, CDSS, CAINS, and the CGI-S. Statistical analysis included Student's t-tests, ANOVA, Pearson correlations, and multiple linear regressions. Results: The average cDBI was 1.3 (SD = 0.9). The model developed explained 40.80 % of the variance. The variable with the greatest weight was the cDBI (B = -11.148, p = 0.010). Negative-expression (B = -2.740, p = 0.011) and negative-experiential (B = -1.175, p = 0.030) symptoms were also associated with lower global cognitive score. However, more years of education (B = 5.140, p < 0.001) and cigarettes per day (B = 1.331, p < 0.001) predicted a better global cognitive score. Conclusion: This study identified specific predictors of global cognition in schizophrenia, with anticholinergic burden emerging as the strongest factor. Our findings underscore the importance of considering the anticholinergic burden of treatments, in addition to negative symptoms, when designing interventions to optimize or maintain cognitive function in patients with schizophrenia.

PsiOvi Staging Model for Schizophrenia (PsiOvi SMS): A New Internet Tool for Staging Patients with Schizophrenia.

BACKGROUND: One of the challenges of psychiatry is the staging of patients, especially those with severe mental disorders. Therefore, we aim to develop an empirical staging model for schizophrenia. METHODS: Data were obtained from 212 stable outpatients with schizophrenia: demographic, clinical, psychometric (PANSS, CAINS, CDSS, OSQ, CGI-S, PSP, MATRICS), inflammatory peripheral blood markers (C-reactive protein, interleukins-1RA and 6, and platelet/lymphocyte [PLR], neutrophil/lymphocyte [NLR], and monocyte/lymphocyte [MLR] ratios). We used machine learning techniques to develop the model (genetic algorithms, support vector machines) and applied a fitness function to measure the model's accuracy (% agreement between patient classification of our model and the CGI-S). RESULTS: Our model includes 12 variables from 5 dimensions: 1) psychopathology: positive, negative, depressive, general psychopathology symptoms; 2) clinical features: number of hospitalizations; 3) cognition: processing speed, visual learning, social cognition; 4) biomarkers: PLR, NLR, MLR; and 5) functioning: PSP total score. Accuracy was 62% (SD = 5.3), and sensitivity values were appropriate for mild, moderate, and marked severity (from 0.62106 to 0.6728). DISCUSSION: We present a multidimensional, accessible, and easy-to-apply model that goes beyond simply categorizing patients according to CGI-S score. It provides clinicians with a multifaceted patient profile that facilitates the design of personalized intervention plans.

What factors should we modify to promote high functioning and prevent functional decline in people with schizophrenia?

Background: Since research in schizophrenia mainly focuses on deficits and risk factors, we need studies searching for high-functioning protective factors. Thus, our objective was to identify protective (PFs) and risk factors (RFs) separately associated with high (HF) and low functioning (LF) in patients with schizophrenia. Methods: We collected information (sociodemographic, clinical, psychopathological, cognitive, and functional) from 212 outpatients with schizophrenia. Patients were classified according to their functional level (PSP) as HF (PSP > 70, n = 30) and LF (PSP ≤ 50, n = 95). Statistical analysis consisted of Chi-square test, Student's t-test, and logistic regression. Results: HF model: variance explained: 38.4-68.8%; PF: years of education (OR = 1.227). RFs: receiving a mental disability benefit (OR = 0.062) and scores on positive (OR = 0.719), negative-expression (OR = 0.711), and negative-experiential symptoms (OR = 0.822), and verbal learning (OR = 0.866). LF model: variance explained: 42.0-56.2%; PF: none; RFs: not working (OR = 6.900), number of antipsychotics (OR = 1.910), and scores on depressive (OR = 1.212) and negative-experiential symptoms (OR = 1.167). Conclusion: We identified specific protective and risk factors for high and low functioning in patients with schizophrenia and confirmed that high functioning factors are not necessarily the opposite of those associated with low functioning. Only negative experiential symptoms are a shared and inverse factor for high and low functioning. Mental health teams must be aware of protective and risk factors and try to enhance or reduce them, respectively, to help their patients improve or maintain their level of functioning.

Is it possible to stage schizophrenia? A systematic review.

INTRODUCTION: A staging model is a clinical tool used to define the development of a disease over time. In schizophrenia, authors have proposed different theoretical staging models of increasing complexity. Therefore, the aims of our study were to provide an updated and critical view of the proposed clinical staging models for schizophrenia and to review the empirical data that support them. METHODS: Systematic literature review following PRISMA guidelines. From the PubMed database and backward reference search, a total of 141 records were retrieved, but only 20 were selected according to the inclusion criteria: (a) available in English; (b) participants with schizophrenia ≥ 18 years; and (c) theoretical and empirical research studies intended to develop, validate, and/or improve staging models of schizophrenia. RESULTS: Different clinical staging models for schizophrenia were identified, information about the proposed stages was tabulated and presented in the Results section (Tables 1, 2). Most of which include neuroimaging, functioning, and psychopathology, but only two models add objective biomarkers and none include patient point of view. However, few models have been psychometrically tested or used small samples and thus have been validated only partially. In addition, five studies proposed therapeutic interventions according to the stage of the disorder from a theoretical point of view. DISCUSSION: In conclusion, it is possible to stage schizophrenia, but the models developed have several limitations. Empirical validation and inclusion of more specific biomarkers and measures of other life areas affected by schizophrenia could help in the development of more valid models.

Does COVID-19 psychological fatigue exist? Results of three online cross-sectional studies conducted in Spain from April 2020 to March 2021.

Background: A previously published meta-analysis found that about one-third of the general population experienced some mental health problem during the early phase of the COVID-19 pandemic, potentially leading to a late mental health crisis. We aimed to describe the acute, short-term, and long-term effects of the COVID-19 pandemic on mental health. Methods: A one-year online survey (S) was conducted in Spain (April 2020 - March 2021). We recruited 18 180 subjects using a virtual respondent-driven snowball sampling method (S1 April 2020, n = 6108; S2 October-November 2020, n = 6418; S3 March 2021, n = 5654). Participants completed the Spanish Depression, Anxiety, and Stress Scale (DASS-21). Results: Overall, our results suggest a progressive increase in the prevalence of anxiety and stress throughout the pandemic waves and relative stability of depression. Women had a greater probability of having depression, anxiety, or stress than men in each survey (P < 0.001). The youngest group (aged 18-24) reported a higher probability (P < 0.05) of having depression, anxiety, or stress than the older groups in S1 and S2. Middle-aged people (25-59) had a greater probability of being a case in the DASS-21 scales than the oldest group (60+), except for depression in men (P = 0.179). In S3, the trend changed: the youngest group showed a decrease in depression and stress while the oldest group showed a dramatic increase (anxiety: men = 664.5%, women = 273.52%; stress: men = 786%, women = 431.37%). Conclusions: It is plausible to conclude that COVID-19 psychological fatigue exists, especially in middle-aged and older adults. Strategies to assist people who have fewer coping skills should be implemented in the near future.

Real-World Functioning in Patients With Schizophrenia: Beyond Negative and Cognitive Symptoms.

Introduction: Interest in the idea of recovery for certain patients with schizophrenia has been growing over the last decade. Improving symptomatology and functioning is crucial for achieving this. Our study aims to identify those factors that substantially contribute to real-world functioning in these patients. Methods: We carried out a cross-sectional study in stable outpatients with schizophrenia on maintenance antipsychotic monotherapy. Patients: We studied 144 outpatients with schizophrenia (DSM-IV-TR criteria) meeting the following criteria: (1) 18-65 years of age; (2) being clinically stable for at least the previous three months; (3) on maintenance antipsychotic monotherapy (prescriptions ≤ 10 mg olanzapine, ≤200 mg quetiapine, or ≤100 mg levomepromazine as hypnotics were also allowed); and (4) written informed consent. Assessment: We collected information on demographic and clinical variables by using an ad hoc questionnaire. For psychopathology, we employed the Spanish versions of the following psychometric instruments: the Positive and Negative Syndrome Scale (PANSS), the Brief Negative Symptom Scale (BNSS-Sp), and the Calgary Depression Scale (CDS). In addition, cognitive domains were assessed using the Verbal Fluency Test (VFT), the Digit Symbol Substitution Test (DSST), and the Trail Making Test, parts A and B (TMT-A and TMT-B). Finally, we employed the Spanish versions of the University of California San Diego Performance-based Skills Assessment (Sp-UPSA) and the Personal and Social Performance (PSP) for assessing functional capacity and real-world functioning, respectively. Statistical analysis: A forward stepwise regression was conducted by entering those variables significantly associated with PSP total score into the univariate analyses (Student's t-test, ANOVA with Duncan's post-hoc test, or bivariate Pearson correlation). Results: A total of 144 patients; mean age 40 years, 64% males, mean length of illness 12.4 years, PSP total score 54.3. The final model was a significant predictor of real-world functioning [F (7, 131) = 36.371, p < 0.001] and explained 66.0% of the variance. Variables retained in the model: BNSS-Sp abulia, asociality, and blunted affect, PANSS general psychopathology, Sp-UPSA transportation, TMT-B, and heart rate. Conclusion: Our model will contribute to a more efficient and personalized daily clinical practice by assigning specific interventions to each patient based on specific impaired factors in order to improve functioning.

Early psychological impact of the 2019 coronavirus disease (COVID-19) pandemic and lockdown in a large Spanish sample.

BACKGROUND: Epidemic outbreaks have significant impact on psychological well-being, increasing psychiatric morbidity among the population. We aimed to describe the early psychological impact of COVID-19 and its contributing factors in a large Spanish sample, globally and according to mental status (never mental disorder NMD, past mental disorder PMD, current mental disorder CMD). METHODS: An online questionnaire was conducted between 19 and 26 March, five days after the official declaration of alarm and the lockdown order. Data included sociodemographic and clinical information and the DASS-21 and IES questionnaires. We analysed 21 207 responses using the appropriate descriptive and univariate tests as well as binary logistic regression to identify psychological risk and protective factors. RESULTS: We found a statistically significant gradient in the psychological impact experienced in five domains according to mental status, with the NMD group being the least affected and the CMD group being the most affected. In the three groups, the depressive response was the most prevalent (NMD = 40.9%, PMD = 51.9%, CMD = 74.4%, F = 1011.459, P < 0.001). Risk factors were female sex and classification as a case in any psychological domain. Protective factors were younger age and ability to enjoy free time. Variables related to COVID-19 had almost no impact except for having COVID-19 symptoms, which was a risk factor for anxiety in all three groups. CONCLUSIONS: Our results can help develop coping strategies addressing modifiable risk and protective factors for each mental status for early implementation in future outbreaks.

The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases.

Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4(+) IFN-γ(+) and CD8(+) IFNγ(+) cells than BM-MSCs. Moreover, compared to BM-MSCs, MenSCs activated with IFN-γ and IL-1ß produced lower amounts of immunosuppressive factors such as IDO, PDL-1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN-γ receptor subunits. In the collagen induced arthritis model, while BM-MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno-GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti-inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno-GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies.

Characterization of menstrual stem cells: angiogenic effect, migration and hematopoietic stem cell support in comparison with bone marrow mesenchymal stem cells.

INTRODUCTION: Stem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity. Besides, menstrual fluid has important advantages over other sources for the isolation of MSCs, including ease of access and repeated sampling in a noninvasive manner. Such attributes allow the rapid culture of MenSCs in numbers that are sufficient for therapeutical doses, at lower cell passages. METHODS: In this study, we advance the characterization of MenSC populations in comparison to bone marrow derived mesenchymal stem cells (BM-MSCs) with regards to proliferation, lineage differentiation, migration potential, secretion profile and angiogenic properties in vitro and in a matrigel plug assay in mice. We additionally tested their ability to support hematopoietic stem cell (HSC) expansion in vitro. RESULTS: The phenotypic analysis of MenSCs revealed a profile largely similar to the BM-MSCs with the exception of a higher expression of the adhesion molecule CD49a (alpha1-integrin). Furthermore, the fibroblast colony forming units (CFU-F) from MenSCs yielded a 2 to 4 fold higher frequency of progenitors and their in vitro migration capacity was superior to BM-MSCs. In addition, MenSCs evidenced a superior paracrine response to hypoxic conditions as evidenced by the secretion of vascular endothelial growth factor and basic fibroblast growth factor and also improved angiogenic effect of conditioned media on endothelial cells. Furthermore, MenSCs were able to induce angiogenesis in a matrigel plug assay in vivo. Thus, an 8-fold increase in hemoglobin content was observed in implanted plugs containing MenSCs compared to BM-MSCs. Finally, we demonstrated, for the first time, the capacity of MenSCs to support the ex-vivo expansion of HSCs, since higher expansion rates of the CD34+CD133+ population as well as higher numbers of early progenitor (CFU-GEMM) colonies were observed in comparison to the BM source. CONCLUSIONS: We present evidence showing superiority of MenSCs with respect to several functional aspects, in comparison with BM-MSCs. However, the impact of such properties in their use as adult-derived stem cells for regenerative3 medicine remains to be clarified.