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.

Lithium response in bipolar disorder: Epigenome-wide DNA methylation signatures and epigenetic aging.

Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups. A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3ß pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed. Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3ß pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response.

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.

Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia.

INTRODUCTION: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). MATERIAL AND METHODS: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. RESULTS: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2=0.091, p=0.001) and functioning (R2=0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003). CONCLUSIONS: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ.

From gut to brain: A network model of intestinal permeability, inflammation, and psychotic symptoms in schizophrenia.

Impaired intestinal permeability has recently been suggested as a possible source of chronic inflammation in schizophrenia, but its association with specific psychopathological features remains uncertain. This study aimed to explore the interaction between intestinal permeability, inflammation, and positive and negative symptoms in schizophrenia using a network analysis approach. The study sample comprised 281 adults with schizophrenia (age 40.29 ± 13.65 years, 63.0 % males), enrolled in a cross-sectional observational study assessing intestinal permeability. We estimated the network with a Gaussian graphical model, incorporating scores from 14 individual items of the Positive and Negative Syndrome Scale (PANSS), along with body mass index (BMI), and plasma C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) levels. We calculated strength centrality and expected influence and used bridge centrality statistics to identify the bridge nodes. Distinct but highly interconnected clusters emerged for positive and negative symptoms. The biological variables were closely associated with each other. LBP was positively linked with CRP and BMI, but only indirectly connected to psychopathology. CRP exhibited direct positive relationships with various PANSS items and bridged LBP and BMI with psychopathology. Bridge nodes included Conceptual Disorganisation (P2), Active Social Avoidance (G16), Suspiciousness/Persecution (P6), and CRP. These findings support the role of gut-derived inflammation as a mechanism underlying greater symptom severity in schizophrenia and emphasise the importance of addressing dietary habits not only to enhance physical health but also to contribute to improving psychotic symptoms.

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.

Psychological impact of the COVID-19 pandemic and lockdown in a Spanish sample with anxiety disorder: sex differences.

The early psychological impact of the COVID-19 pandemic and lockdown is greater in people with mental disorders. This study explored the differences in the psychological impact on people with an anxiety disorder by sex in Spain.

Impacto psicológico de la pandemia de COVID-19 y el confinamiento en una muestra española con trastorno de ansiedad: diferencias entre sexos / Psychological impact of the covid-19 pandemic and lockdown in a spanish sample with anxiety disorder: sex differences

Introducción. El impacto psicológico en las etapas iniciales de la pandemia por COVID-19 y el confinamiento fue mayor en personas con trastornos mentales. En este estudio se exploraron las diferencias en el impacto psicológico según el sexo en personas con trastorno de ansiedad en España. Metodología. Estudio transversal, descriptivo y comparativo de los datos aportados por los participantes en una encuesta online anónima realizada entre el 19 y el 26 de marzo de 2020. El cuestionario ad hoc incluyó datos sociodemográficos, clínicos y variables relacionadas con COVID-19,junto con preguntas sobre estrategias de afrontamiento y las versiones en español de la Escala de Escalas de Depresión Ansiedad Estrés (DASS-21) y la Escala de Impacto del Estresor(IES). Se utilizaron análisis descriptivos bivariados y modelos de regresión logística. Resultados. De los 21.207 participantes, se analizaron1617 (7,6%) personas con trastorno de ansiedad autoinformado [1347 (83,3%) mujeres; 270 (16,7%) varones]. El impacto psicológico fue mayor en las mujeres que en los hombres con diferencias estadísticamente significativas en cada subescala del DASS-21 y subescalas del IES. Después de ajustar por posibles variables de confusión, se observó que ser mujer se asoció con puntuaciones más altas en las subescalas de pensamientos intrusivos y evitativos. Conclusiones. Nuestro estudio sugiere que las mujeres con trastorno de ansiedad son un grupo vulnerable a un mayor impacto negativo en la salud mental y, especialmente, en los síntomas relacionados con el trastorno de estrés postraumático. (AU)

Background. The early psychological impact of the COVID-19 pandemic and lockdown is greater in peoplewith mental disorders. This study explored the differences in the psychological impact on people with an anxiety disorder by sex in Spain. Methods. Cross-sectional, descriptive, comparative study of the data provided by participants in an anonymous online survey between March 19 and 26, 2020. Thead hoc questionnaire included sociodemographic, clinical,and variable data related to COVID-19, along with questions about coping strategies, and the Spanish versions ofthe Depression, Anxiety, and Stress Scale (DASS-21) andImpact of Event Scale (IES). Descriptive bivariate analyses and logistic regression models were used. Results. Of the 21,207 participants, 1617 (7.6%) people with self-reported anxiety disorder were analyzed [1347(83.3%) females; 270 (16.7%) males]. The psychological impact was greater on women than men with statistically significant differences in each subscale of the DASS-21and subscales of the IES. After adjusting for potential confounding variables, it was observed that being awoman was associated with higher scores on the intrusiveand avoidant thoughts subscales. Conclusions. Our study suggests that women with ananxiety disorder are a group vulnerable to a greater negative impact on mental health and, especially, symptomsr elated to post-traumatic stress disorder. (AU)

Intestinal permeability and low-grade chronic inflammation in schizophrenia: A multicentre study on biomarkers. Rationale, objectives, protocol and preliminary results.

BACKGROUND: Altered intestinal permeability and low-grade chronic inflammation disrupt the integrity of the blood-brain barrier (microbiota-gut-brain axis), probably playing a role in the pathophysiology of schizophrenia-spectrum disorders. However, studies assessing the microbiota-gut-brain axis are inconsistent. This article describes the rationale, objectives, protocol, and presents descriptive results for a new project. METHODS: The sample of this study came from an observational, cross-sectional and multisite study including four centers in Spain (PI17/00246) recruiting adult patients with DSM-5 schizophrenia-spectrum disorders at any stage of the disease. The aims of the project are to assess the interrelation between intestinal permeability and low-grade chronic inflammation in schizophrenia-spectrum disorders and the role of peripheral biomarkers, diet, exercise, metabolic syndrome, disease severity and functioning as well as cognition. Assessments included the following variables: (1) anthropometric, (2) intestinal permeability, diet, and physical exercise, (3) clinical and functional, (4) neuropsychological and cognitive reserve, and (5) peripheral biomarkers from blood. RESULTS: A total of 646 patients were enrolled (257, 39.7% female). Mean age was 43.2±13.6 years, illness duration 15.1±11.5 years. 55.8% consumed tobacco. Positive PANSS score was 13.68±6.55, and 20.38±8.69 in the negative symptoms. CGI was 4.16±2.22 and GAF was 60.00±14.84. CONCLUSION: The results obtained by this project are expected to contribute toward the understanding of the physiopathology of schizophrenia-spectrum disorders. This will likely aid to personalize treatments in real-world clinical practice, potentially including variables related to intestinal permeability and inflammation.

Platelet and white blood-cell-based ratios: Differential inflammatory markers of severe mental disorders?

INTRODUCTION: Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios, and systemic inflammatory index (SII) represent peripheral markers of inflammation associated with different severe mental disorders. MATERIAL AND METHODS: In this study, these parameters were analyzed in a sample of 622 participants [197 patients with major depressive disorder (MDD), 154 with bipolar disorder (BD), 176 with schizophrenia (SCH), and 95 healthy controls (HC)]. Sociodemographic and clinical data of patients were recorded. RESULTS: Differences in age and sex were detected among groups (p<0.001), with SCH patients being younger and MDD patients being older. After stratifying by sex, these ratios were compared using the nonparametric ANCOVA (Quade's test) using age as a covariate. In males, no significant statistical differences were found between groups. However, differences were observed in MLR in the subgroup of females [MDD: 0.23 (SD=0.09); BD: 0.23 (SD=0.11); SCH: 0.24 (SD=0.11); HC: 0.29 (SD=0.13); F=5.376, p=0.001]. Post hoc testing revealed that there are MLR differences between HC versus MDD and between HC versus BD, with higher values in HC versus the other two groups. On the other hand, no differences were found in either males or females for any of the studied ratios, among the three diagnostic groups. CONCLUSIONS: MLR is reduced in MDD and BD patients versus HC, but exclusively in the female group. However, based on the analyzed indices, it is not possible to differentiate among the three diagnostic groups of patients. As a limitation of this study, note that the effects of psychopharmacological treatments and smoking have not been controlled for.

Endocrine biomarkers related to sleep-wake cycle and sleep disturbances in patients with bipolar disorder: A systematic review

Background and objectives: Sleep and circadian disturbances have been widely studied in patients with bipolar disorder. However, there is no clear evidence about the role of peripheral biomarkers of the circadian cycle in this population. This systematic review aims to identify potential endocrine blood biomarkers of circadian rhythms and study their relationship with sleep problems in these patients.MethodsAn electronic search was performed of PubMed and PsycINFO databases. It included articles about the topic from 1991 through 2021. The search strategy was: ("peripheral biomarkers" OR "biological markers" OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR "circadian rhythm" OR sleep OR insomnia) AND "bipolar."ResultsAfter excluding duplicates, 92 records were obtained. Only 5 studies met the inclusion criteria (n=499; bipolar disorder=125; unipolar depression=148; schizophrenia=80; controls=146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study), and orexin-A (1 study). Overall, no significant associations were detected between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures.ConclusionThis review highlights the lack of studies exploring the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in bipolar disorder. (AU)

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial.

BACKGROUND: Network analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes. METHODS: Baseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes. RESULTS: Nodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value. CONCLUSIONS: The current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.

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.

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia.

INTRODUCTION: Apathy is a negative symptom of schizophrenia and is associated with poor real world functioning. Therefore, it is important to have validated psychometric instruments to assess this symptom. This is the first study to validate the Spanish adaptation of the self-rated version of the Apathy Assessment Scale (AES-S) in patients with schizophrenia. MATERIALS AND METHODS: Naturalistic, cross-sectional, validation study in 104 patients with schizophrenia evaluated using the following scales: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS), and Apathy Evaluation Scale-self-rated version (AES-S). RESULTS: Reliability: Internal consistency (Cronbach's alpha) was 0.908. Convergent validity: The Pearson correlation coefficient between AES-S and CAINS-MAP total scores was -0.483 (p<0.001). For SNS, total and avolition subscale scores were -0.803 and -0.639 (p<0.001), respectively. With the MAP-SR, the correlation coefficient was -0.727 (p<0.001). Divergent validity: The Pearson correlation coefficient between AES-S and PSP total scores was 0.504 (p<0.001). Furthermore, with the CDSS, the correlation coefficient was -0.431 (p<0.001). Discriminant validity: The AES-S discriminated between different levels of illness severity according to CGI-S scores. Factor analysis: A three-component solution explained 57.32% of the variance. Pearson correlations between coefficients were 1-2=0.265, 1-3=0.464, and 2-3=0.060. CONCLUSION: The Spanish AES-S is a reliable and valid instrument for assessing apathy in Spanish patients with schizophrenia. It seems to be appropriate for use in everyday clinical practice as a means of monitoring apathy in these patients.

Validation of a European Spanish-version of the Self-Evaluation of Negative Symptoms (SNS) in patients with schizophrenia.

INTRODUCTION: Negative symptoms can be grouped into five domains: apathy/avolition, anhedonia, asociality, alogia, and affective flattening. There are few validate self-rated measures that assess these five dimensions. Therefore, this study aimed to validate the Self-Evaluation of Negative Symptoms (SNS) in Spanish patients with schizophrenia. MATERIAL AND METHODS: Cross-sectional, validation study in 104 outpatients with schizophrenia evaluated using the Spanish version of the following scales: Clinical Assessment Interview for Negative Symptoms (CAINS), Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale for Schizophrenia (CGI-SCH), Personal and Social Performance (PSP), Motivation and Pleasure Scale - Self-Report (MAP-SR), 36-item Short-Form Health Survey (SF-36) and the Self-Evaluation of Negative Symptoms (SNS). RESULTS RELIABILITY: Internal consistency (Cronbach's alpha) was 0.915. Convergent validity: The Pearson correlation coefficient between MAP-SR and SNS Total scores was 0.660 (p<0.001). For PANSS-N, the correlation was 0.437 (p<0.005) and with the CAINS-Total was 0.478 (p<0.005). Divergent validity: The Pearson correlation coefficient between SNS and PSP was r=-0.372 (p≤0.001), and with SF-36 Physical and Mental Summary Component scores were r=-0.213 (p=0.066) and r=-0.144 (p=0.219), respectively. Discriminant validity: SNS Total scores were significantly statistically different according to the severity of the negative symptomatology rated by the CGI-SCH negative scale (p<0.001). CONCLUSION: The SNS is a reliable and valid instrument to self-rate the five domains of negative symptoms in patients with schizophrenia and seems to be appropriate for use in everyday clinical practice as a complementary measure to the evaluation performed by the clinician.