Highly Sensitive Microsatellite Instability and Immunohistochemistry Assessment in Endometrial Aspirates as a Tool for Cancer Risk Individualization in Lynch Syndrome.

Women with Lynch syndrome (LS) are at increased risk of endometrial cancer (EC), among other tumors, and are characterized by mismatch repair (MMR) deficiency and microsatellite instability (MSI). While risk-reducing gynecologic surgeries effectively decrease EC incidence, doubts arise regarding the appropriate timing of the surgery. We explored the usefulness of highly sensitive MSI (hs-MSI) assessment in endometrial aspirates for individualizing gynecologic surveillance in LS carriers. Ninety-three women with LS, 25 sporadic EC patients (9 MMR-proficient and 16 MMR-deficient), and 30 women with benign gynecologic disease were included in this study. hs-MSI was assessed in prospectively collected endometrial aspirates in 67 LS carriers, EC cases, and controls. MMR, PTEN, ARID1A, and PAX2 protein expression patterns were evaluated in the LS samples. Follow-up aspirates from 8 LS carriers were also analyzed. Elevated hs-MSI scores were detected in all aspirates from MMR-deficient EC cases (3 LS and 16 sporadic) and negative in aspirates from controls and MMR-proficient EC cases. Positive hs-MSI scores were also detected in all 4 LS aspirates reported as complex hyperplasia. High hs-MSI was also present in 10 of 49 aspirates (20%) from LS carriers presenting a morphologically normal endometrium, where MMR protein expression loss was detected in 69% of the samples. Interestingly, the hs-MSI score was positively correlated with MMR-deficient gland density and the presence of MMR-deficient clusters, colocalizing PTEN and ARID1A expression loss. High hs-MSI scores and clonality were evidenced in 2 samples collected up to 4 months before EC diagnosis; hs-MSI scores increased over time in 5 LS carriers, whereas they decreased in a patient with endometrial hyperplasia after progestin therapy. In LS carriers, elevated hs-MSI scores were detected in aspirates from premalignant and malignant lesions and normal endometrium, correlating with MMR protein loss. hs-MSI assessment and MMR immunohistochemistry may help individualize EC risk assessment in women with LS.

Role of psychological background in cancer susceptibility genetic testing distress: It is not only about a positive result.

Clinical and familial factors predict psychological distress after genetic testing for cancer susceptibility. However, the contribution of an individual's psychological background to such distress is unclear. This study aims to analyze the psychological impact of genetic testing and to identify the profile of individuals at higher risk. This is a longitudinal multicenter study of individuals undergoing genetic testing for cancer susceptibility. Demographic, clinical, genetic, familial, and psychological (personality types, cancer worry) characteristics were assessed by validated questionnaires the day of genetic testing. Distress, uncertainty, and positive experience perception (MICRA scale) were evaluated at the results disclosure visit, and 3 and 12 months afterwards. Multivariate analysis was performed. A total of 714 individuals were included. A high neuroticism score, high baseline cancer worry, and a positive genetic test result were independently associated with higher psychological impact (p-value < 0.05). The highest risk profile (10% of the cohort) included women with high level of neuroticism and a positive result. Uncertainty was mainly associated with a high level of neuroticism, regardless of the genetic test result. A holistic approach to personalized germline genetic counseling should include the assessment of personality dimensions.

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.

Validation of a European Spanish-version of the Self-Evaluation of Negative Symptoms (SNS) in patients with schizophrenia / Validación de la versión española de SNS (Self-Evaluation of Negative Symptoms-Autoevaluación de síntomas negativos) en pacientes esquizofrénicos

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). (AU)

Introducción:Los síntomas negativos pueden agruparse en 5 dominios: apatía/abulia, anhedonia, conductas asociales, afasia y aplanamiento afectivo. Existen pocas medidas validadas autocalificadas que evalúen estas 5 dimensiones. Por tanto, el objetivo de este estudio fue validar la herramienta Self-Evaluation of Negative Symptoms (SNS, Autoevaluación de síntomas negativos) en pacientes españoles esquizofrénicos.Material y métodos:Estudio transversal de validación en 104 pacientes esquizofrénicos externos, evaluados utilizando la versión española de las escalas siguientes: 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) y la SNS.Resultados: Respecto a la fiabilidad,la consistencia interna (α de Cronbach) fue de 0,915. En cuanto a validez convergente, el coeficiente de correlación de Pearson entre las puntuaciones totales de MAP-SR y SNS fue de 0,660 (p < 0,001). Para PANSS-N, la correlación fue de 0,437 (p < 0,005) y de 0,478 (p < 0,005) con CAINS-Total. Respecto a la validez divergente, el coeficiente de correlación de Pearson entre las puntuaciones SNS y PSP fue de r = –0,372 (p ≤ 0,001) y con las puntuaciones de SF-36 Physical and Mental Summary Component fueron de r = −0,213 (p = 0,066) y r = −0,144 (p = 0,219), respectivamente. En la validez discriminante, las puntuaciones totales de SNS fueron diferentes desde un punto de vista estadístico significativo, conforme a la gravedad de la sintomatología negativa calificada por la escala negativa CGI-SCH (p < 0,001). (AU)

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia / Validación de la adaptación a español de Europa de la versión de auto-evaluación de la escala de evaluación de la apatía (AES-S) en pacientes esquizofrénicos

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. (AU)

Introducción: La apatía es un síntoma negativo de la esquizofrenia, y está asociada a un mal funcionamiento del mundo real. Por tanto, es importante disponer de instrumentos psicométricos validados para valorar este síntoma. Este es el primer estudio que valida la adaptación al español de la versión auto-evaluada de la escala de evaluación de la apatía (AES-S) en pacientes esquizofrénicos.Material y métodos: Estudio naturalista, transversal y de validación realizado en 104 pacientes esquizofrénicos evaluados utilizando las escalas siguientes: 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) y Apathy Evaluation Scale-self-rated version (AES-S).Resultados: Fiabilidad: La consistencia interna (alfa de Cronbach) fue de 0,908. Validez convergente: El coeficiente de correlación de Pearson entre las puntuaciones totales de AES-S y CAINS-MAP fue de −0,483 (p<0,001). Para SNS, las puntaciones totales y de la subescala de abulia fueron de −0,803 y −0,639 (p<0,001), respectivamente. En cuanto a la escala MAP-SR, el coeficiente de correlación fue de −0,727 (p<0,001). Validez divergente: El coeficiente de correlación de Pearson entre las puntuaciones totales de AES-S y PSP fue de 0,504 (p<0,001). Además, en la escala CDSS, el coeficiente de correlación fue de −0,431 (p<0,001). Validez discriminante: La escala AES-S discriminó entre los diferentes niveles de gravedad de la enfermedad, conforme a las puntuaciones CGI-S. Análisis factorial: Una solución de tres componentes explicó el 57,32% de la varianza. Las correlaciones de Pearson entre los coeficientes fueron de 1-2=0,265, 1-3=0,464 y 2-3=0,060. (AU)

Paired Somatic-Germline Testing of 15 Polyposis and Colorectal Cancer-Predisposing Genes Highlights the Role of APC Mosaicism in de Novo Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing. Paired samples of colorectal polyps, tumors, and/or mucosa were analyzed using a custom next-generation sequencing panel targeting 15 polyposis and CRC-predisposing genes. Whenever possible, the extension of mosaicism to blood or sperm was also examined. Of 11 patients with classic adenomatous polyposis, a mosaic pathogenic variant in APC was identified in 7 (64%). No other altered genes were identified. In two of seven patients (29%), mosaicism was found restricted to colonic tissues, whereas in five of seven patients (71%), it was extended to the blood. Germline affectation was confirmed in one patient. We report the first analysis at a somatic level of 15 genes associated with CRC susceptibility, which highlights the role of APC mosaicism in classic FAP etiology. The results further reinforce the importance of testing target tissues when blood test results are negative.

Spanish Validation of the MAP-SR: Two Heads Better Than One for the Assessment of Negative Symptoms of Schizophrenia.

BACKGROUND: There is little research on self-reported negative symptomatology measures in schizophrenia. The aims of this study were to validate the Spanish version of the Motivation and Pleasure Scale-Self-Report (MAP-SR) and determine the concordance between patient-reported outcome measures for reflecting the severity of negative symptoms of schizophrenia and clinician-rated outcome measures. METHOD: A sample of 174 subjects who completed the MAP-SR and 104 who completed the Self-Evaluation of Negative Symptoms (SNS) were analyzed. The clinician-reported outcome measures (CROMs) were the Spanish versions of the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Positive and Negative Syndrome Scale (PANSS), while the patient-reported outcome measures (PROMs) were MAP-SR and SNS. Cronbach's a, bivariate analyses and Lin's concordance correlation coefficient (CCC) were calculated. RESULTS: The Spanish version of the MAP-SR demonstrated excellent reliability (Cronbach's α=.923). Its correlation coefficients were higher with CAINS [CAINS-Total: r=.608, p<.005; CAINS-Motivation and Pleasure subscale(CAINS-MAP): r=.662, p<.005] than with PANSS negative scales [PANSS-Negative scale(PANSS-N): r=.393, p<.005; PANSS-Marder Negative Factor(PANSS-MNF): r=.478, p<.005]. Finally, concordance between clinician and patient ratings was low in all cases, varying from a CCC of 0.661 to .392. CONCLUSIONS: We found poor concordance between patient and clinician ratings, hence we believe that the two evaluations are not mutually exclusive but complementary.

Factors associated with alcohol and tobacco consumption as a coping strategy to deal with the coronavirus disease (COVID-19) pandemic and lockdown in Spain.

AIM: To provide a population-based characterization of sociodemographic and clinical risk and protective factors associated with consumption of alcohol, tobacco, or both as a coping strategy in a sample of the Spanish general population during the early phase of the COVID-19 pandemic. METHODS: Cross-sectional study based on an online snowball recruiting questionnaire. The survey consisted of an ad hoc questionnaire comprising clinical and sociodemographic information and the Spanish versions of the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). RESULTS: The final sample included 21,207 individuals [mean age (SD) = 39.7 (14.0); females: 14,768 (69.6%)]. Up to 2867 (13.5%) of participants reported using alcohol, 2545 (12%) tobacco and 1384 (6.5%) both substances as a strategy to cope with the pandemic. Sex-related factors were associated with alcohol consumption as a coping strategy [female, OR = 0.600, p < 0.001]. However, education level, work status, and income played different roles depending on the substance used to cope. Having a current mental disorder was associated only with tobacco consumption as a coping strategy [OR = 1.391, p < 0.001]. Finally, sex differences were also identified. CONCLUSIONS: Sociodemographic, clinical, and psychological factors were associated with consumption of alcohol, tobacco, or both as a coping method for the COVID-19 pandemic and lockdown. Our findings may help develop specific intervention programs reflecting sex differences, which could minimize negative long-term outcomes of substance use after this pandemic.

Patients' and professionals' perspective of non-in-person visits in hereditary cancer: predictors and impact of the COVID-19 pandemic.

PURPOSE: To identify predictors of patient acceptance of non-in-person cancer genetic visits before and after the COVID-19 pandemic and assess the preferences of health-care professionals. METHODS: Prospective multicenter cohort study (N = 578, 1 February 2018-20 April 2019) and recontacted during the COVID-19 lockdown in April 2020. Health-care professionals participated in May 2020. Association of personality traits and clinical factors with acceptance was assessed with multivariate analysis. RESULTS: Before COVID-19, videoconference was more accepted than telephone-based visits (28% vs. 16% pretest, 30% vs. 19% post-test). Predictors for telephone visits were age (pretest, odds ratio [OR] 10-year increment = 0.79; post-test OR 10Y = 0.78); disclosure of panel testing (OR = 0.60), positive results (OR = 0.52), low conscientiousness group (OR = 2.87), and post-test level of uncertainty (OR = 0.93). Predictors for videoconference were age (pretest, OR 10Y = 0.73; post-test, OR 10Y = 0.75), educational level (pretest: OR = 1.61), low neuroticism (pretest, OR = 1.72), and post-test level of uncertainty (OR = 0.96). Patients' reported acceptance for non-in-person visits after COVID-19 increased to 92% for the pretest and 85% for the post-test. Health-care professionals only preferred non-in-person visits for disclosure of negative results (83%). CONCLUSION: These new delivery models need to recognize challenges associated with age and the psychological characteristics of the population and embrace health-care professionals' preferences.

Comparative effects of viral-transport-medium heat inactivation upon downstream SARS-CoV-2 detection in patient samples.

Introduction. The COVID-19 pandemic, which began in 2020 is testing economic resilience and surge capacity of healthcare providers worldwide. At the time of writing, positive detection of the SARS-CoV-2 virus remains the only method for diagnosing COVID-19 infection. Rapid upscaling of national SARS-CoV-2 genome testing presented challenges: (1) Unpredictable supply chains of reagents and kits for virus inactivation, RNA extraction and PCR-detection of viral genomes. (2) Rapid time to result of <24 h is required in order to facilitate timely infection control measures.Hypothesis. Extraction-free sample processing would impact commercially available SARS-CoV-2 genome detection methods.Aim. We evaluated whether alternative commercially available kits provided sensitivity and accuracy of SARS-CoV-2 genome detection comparable to those used by regional National Healthcare Services (NHS).Methodology. We tested several detection methods and tested whether detection was altered by heat inactivation, an approach for rapid one-step viral inactivation and RNA extraction without chemicals or kits.Results. Using purified RNA, we found the CerTest VIASURE kit to be comparable to the Altona RealStar system currently in use, and further showed that both diagnostic kits performed similarly in the BioRad CFX96 and Roche LightCycler 480 II machines. Additionally, both kits were comparable to a third alternative using a combination of Quantabio qScript one-step Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) mix and Centre for Disease Control and Prevention (CDC)-accredited N1 and N2 primer/probes when looking specifically at borderline samples. Importantly, when using the kits in an extraction-free protocol, following heat inactivation, we saw differing results, with the combined Quantabio-CDC assay showing superior accuracy and sensitivity. In particular, detection using the CDC N2 probe following the extraction-free protocol was highly correlated to results generated with the same probe following RNA extraction and reported clinically (n=127; R2=0.9259).Conclusion. Our results demonstrate that sample treatment can greatly affect the downstream performance of SARS-CoV-2 diagnostic kits, with varying impact depending on the kit. We also showed that one-step heat-inactivation methods could reduce time from swab receipt to outcome of test result. Combined, these findings present alternatives to the protocols in use and can serve to alleviate any arising supply-chain issues at different points in the workflow, whilst accelerating testing, and reducing cost and environmental impact.

Alcohol use and risk factors for self-harm behavior in Spanish adolescents. / Consumo de alcohol y factores de riesgo de conductas autolesivas en adolescentes españoles.

Self-harm behaviors in children and adolescents constitute an important public health problem with prevalence figures in the clinical population between 40 and 80%. The objectives of the study were to analyze and compare the Spanish sub-samples of two studies, SEYLE and WE-STAY to determine prevalence, self-harm patterns and factors associated with self-harm behaviors, notably the use of alcohol or drugs. The questionnaires used in both studies were the Global School Health Survey (GSHS), the Beck Depression Inventory (BDI-II), the Strengths and Difficulties Questionnaire (SDQ). The self-harm behaviors were evaluated with a modified 6-item version of s the Deliberate Self-Harm Inventory (DSHI). The independence of the study's categorical variables was assessed using the Chi-square test. The change in the relative risk of self-harm between the SEYLE study and WE-STAY was evaluated through the odds ratio (OR) calculation. Two different logistic regression models were calculated in order to establish the factors associated with self-harm behaviors in each study. In the present study, the rates of DSH vary according to study and sex, ranging from 0.58% to 2.08%, and different patterns of self-harm are evidenced by sex, with males self-injuring more frequently by self-inflicted blows and burns, while young women more often cut themselves. The presence of depressive symptoms and alcohol use were the factors most strongly associated with an increased risk of DSH.

Las conductas autolesivas en niños y adolescentes constituyen un importante problema de salud pública con cifras de prevalencia en la población clínica entre el 40 y 80%. Los objetivos del estudio son analizar y comparar las submuestras españolas de dos trabajos, SEYLE y WE-STAY, para conocer la prevalencia, los patrones de autolesión y los factores asociados a las conductas autolesivas, en particular el consumo de alcohol o drogas. Los cuestionarios utilizados en ambos estudios fueron la Encuesta Global de Salud Escolar (GSHS), el Inventario de Depresión de Beck (BDI-II), el Cuestionario de Fortalezas y Dificultades (SDQ). Los comportamientos autolesivos fueron evaluados con una versión modificada de 6 ítems basada en el Inventario de Autolesiones Deliberadas (DSHI). La independencia de las variables categóricas del estudio se evaluó mediante la prueba Ji-Cuadrado. El cambio en el riesgo relativo de autolesión entre el estudio SEYLE y WE-STAY, se evaluó a través del cálculo de odds ratio (OR). Se calcularon dos modelos de regresión logística diferentes con el fin de establecer los factores asociados con comportamientos autolesivos en cada estudio. En el presente estudio las tasas de DSH varían en función del estudio y del sexo en un rango entre 0,58% y 2,08%, presentando patrones de autolesiones diferentes según el sexo, los hombres se autolesionaron más frecuentemente mediante golpes autoinfligidos y quemaduras, mientras que las mujeres se hicieron más frecuentemente cortes. La presencia de síntomas depresivos y el consumo de alcohol fueron los factores asociados de forma más robusta a un mayor riesgo de DSH.

Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits.

BACKGROUND: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide. METHOD: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. RESULTS: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included. In general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters. LIMITATIONS: The number of papers included in this review is limited to the few studies using non-attempter clinically-matched control group and therefore results regarding diagnosis, symptomatology and time of the attempt are modest and contradictory. CONCLUSIONS: Patients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide.

Consumo de alcohol y factores de riesgo de conductas autolesivas en adolescentes españoles / Alcohol use and risk factors for self-harm behavior in Spanish adolescents

Las conductas autolesivas en niños y adolescentes constituyen un importante problema de salud pública con cifras de prevalencia en la población clínica entre el 40 y 80%. Los objetivos del estudio son analizar y comparar las submuestras españolas de dos trabajos, SEYLE y WE-STAY, para conocer la prevalencia, los patrones de autolesión y los factores asociados a las conductas autolesivas, en particular el consumo de alcohol o drogas. Los cuestionarios utilizados en ambos estudios fueron la Encuesta Global de Salud Escolar (GSHS), el Inventario de Depresión de Beck (BDI-II), el Cuestionario de Fortalezas y Dificultades (SDQ). Los comportamientos autolesivos fueron evaluados con una versión modificada de 6 ítems basada en el Inventario de Autolesiones Deliberadas (DSHI). La independencia de las variables categóricas del estudio se evaluó mediante la prueba Ji-Cuadrado. El cambio en el riesgo relativo de autolesión entre el estudio SEYLE y WE-STAY, se evaluó a través del cálculo de odds ratio (OR). Se calcularon dos modelos de regresión logística diferentes con el fin de establecer los factores asociados con comportamientos autolesivos en cada estudio. En el presente estudio las tasas de DSH varían en función del estudio y del sexo en un rango entre 0,58% y 2,08%, presentando patrones de autolesiones diferentes según el sexo, los hombres se autolesionaron más frecuentemente mediante golpes autoinfligidos y quemaduras, mientras que las mujeres se hicieron más frecuentemente cortes. La presencia de síntomas depresivos y el consumo de alcohol fueron los factores asociados de forma más robusta a un mayor riesgo de DSH

Self-harm behaviors in children and adolescents constitute an important public health problem with prevalence figures in the clinical population between 40 and 80%. The objectives of the study were to analyze and compare the Spanish sub-samples of two studies, SEYLE and WE-STAY to determine prevalence, self-harm patterns and factors associated with self-harm behaviors, notably the use of alcohol or drugs. The questionnaires used in both studies were the Global School Health Survey (GSHS), the Beck Depression Inventory (BDI-II), the Strengths and Difficulties Questionnaire (SDQ). The self-harm behaviors were evaluated with a modified 6-item version of s the Deliberate Self-Harm Inventory (DSHI). The independence of the study's categorical variables was assessed using the Chi-square test. The change in the relative risk of self-harm between the SEYLE study and WE-STAY was evaluated through the odds ratio (OR) calculation. Two different logistic regression models were calculated in order to establish the factors associated with self-harm behaviors in each study. In the present study, the rates of DSH vary according to study and sex, ranging from 0.58% to 2.08%, and different patterns of selfharm are evidenced by sex, with males self-injuring more frequently by self-inflicted blows and burns, while young women more often cut themselves. The presence of depressive symptoms and alcohol use were the factors most strongly associated with an increased risk of DSH

The Mediating Role of Impulsivity in the Relationship Between Suicidal Behavior and Early Traumatic Experiences in Depressed Subjects.

Background: Depressed patients with early traumatic experiences may represent a clinically and biologically distinct subtype, with worse clinical outcomes and greater risk of suicide. Since early traumatic experiences alter development of systems that regulate the stress response, increasing sensitivity to stress and mood disorders later in life, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behavior. Objective: To determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behavior in patients with major depressive disorder (MDD). Methods: The total sample consists of 190 patients [mean age (SD) = 53.71 (10.37); females: 66.3%], with current MDD (DSM-5 criteria). The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity, respectively. We developed mediation models by bootstrap sampling methods. Results: Eighty-one (42.6%) patients had a history of previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were significantly higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b = 0.007, 95% CI = 0.001, 0.015), after statistically controlling for sex, the HDRS-Total, and the LTE-Total. Discussion: Data suggest that impulsivity could mediate the influence of childhood trauma on suicidal behavior. This will help understand the role of risk factors in suicidal behavior and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.

Cognitive impairment and C-reactive protein in clinically stable schizophrenia outpatients: a focus on sex differences.

Although previous findings identified an association between C-reactive protein (CRP) levels, and impaired cognitive functions in patients with schizophrenia (SZ), little is currently known about the relationship between inflammation, cognition, and sex in SZ. The current study aimed to explore the association between peripheral inflammation and cognitive impairment in SZ as a function of sex. The sample included 132 clinically stable patients with SZ, of whom 82 were males (62.1%) and 50 females (37.9%). Sociodemographic data were collected, an accurate assessment was performed using the Positive and Negative Syndrome (PANSS), Clinical Assessment Interview for Negative Symptoms (CAINS), and Calgary Depression (CDS) scales, and the MATRICS Consensus Cognitive Battery (MCCB), and CRP levels were tested. A Pearson correlation and multiple regression analyses, including potential confounding factors, were performed. We found an inverse association between CRP levels and performance on visual learning (r = - 0.386, p = 0.006) domain in female patients only, whereas no correlations were found in males. The regression model for women retained age (ß = - 0.319, p = 0.017), the CAINS-MAP score (ß = - 0.247, p = 0.070), and the CRP (ß = - 0.321, p = 0.013) as predictors of visual learning. Our results suggest the possible existence of sex-specific modulation of the association between systemic inflammation and the cognitive features of the illness.

Early Psychological Correlates Associated With COVID-19 in A Spanish Older Adult Sample.

OBJECTIVE: Main aims of the study are to examine the early psychological correlates associated with the COVID-19 pandemic and lockdown on the mental health of a Spanish older adult sample and to analyze the influence of past mental disorder (PMD) and current mental disorder (CMD) on those correlates. METHODS: Cross-sectional study based on an online snowball recruiting questionnaire. Psychological correlates assessed with the Depression, Anxiety, and Stress Scale (DASS-21) and Impact of Event Scale (IES). Binary and multinomial logistic regression models were used to identify risk and protective factors. RESULTS: Final sample included 2,194 individuals aged 60 years or more (mean age [SD]: 65.62 [5.05]; females: 1,198 [54.6%]). There were 342 (15.6%) individuals who reported a PMD and 162 (7.4%) who reported a CMD. Avoidant (32.1%) and depressive (25.6%) styles were the most prevalent, regardless of mental health status. Main risk factors for negative affectivity were female gender and history CMD or PMD. However, job stability and the ability to enjoy free time were generally associated with better outcomes. No differences were found in psychological correlates between those with no lifetime history of mental disorder versus PMD on the DASS-21 or IES. However, CMD was associated with higher anxiety scores on the DASS-21 (odds ratio: 1.838, p < .001). CONCLUSION: Regardless of mental status, avoidant and depressive styles were the most prevalent in this older adult sample. Main protective factor in all subgroups was the ability to enjoy free time, whereas the main risk factors were being female and current or past history of mental disorder.

Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients.

CHEK2 variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describe CHEK2 variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, three CHEK2 frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the whole CHEK2 coding region was analyzed by next-generation sequencing in 1848 prospective patients with HC suspicion. We refined ACMG-AMP criteria and applied different combined rules to classify CHEK2 variants and define risk alleles. We identified 10 CHEK2 null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; two can also be considered "established risk-alleles" and one as "likely risk-allele." The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary nonpolyposis colorectal cancer patients). Here, we provide ACMG adjustment guidelines to classify CHEK2 variants. We hope that this study would be useful for variant classification of other genes with low effect variants.

Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.

The causal mechanism for cancer predisposition in Lynch-like syndrome (LLS) remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive (epi)genetic analysis. One hundred and fifteen LLS patients harboring MMR-deficient tumors and no germline MMR mutations were included. Mutational analysis of 26 colorectal cancer (CRC)-associated genes was performed. Pathogenicity of MMR variants was assessed by splicing and multifactorial likelihood analyses. Genome-wide methylome analysis was performed by the Infinium Human Methylation 450K Bead Chip. The multigene panel analysis revealed the presence of two MMR gene truncating mutations not previously found. Of a total of 15 additional MMR variants identified, five -present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes were found in 12 probands. Methylome analysis detected one constitutional MLH1 epimutation, but no additional differentially methylated regions were identified in LLS compared to LS patients or cancer-free individuals. In conclusion, the use of an ad-hoc designed gene panel combined with pathogenicity assessment of variants allowed the identification of deleterious MMR mutations as well as new LLS candidate causal genes. Constitutional epimutations in non-LS-associated genes are not responsible for LLS.

Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts.

Suicide is the leading cause of non-natural death worldwide, and major depressive disorder (MDD) is the mood disorder with the highest prevalence among individuals with suicidal behaviour (SB). The role of inflammation and immunomodulation in mood disorders has raised interest in recent years, as inflammation biomarkers have been reported to be increased in mood disorder patients, suggesting a role of inflammation in their pathogenesis. The influence of inflammation on the haematopoietic production is well known; however, a comprehensive study of the haematopoietic production in patients with major depressive episodes (MDE) is lacking. We examined global haematopoietic parameters from complete blood counts (CBC) of patients with MDE, in search of prognostic patterns. MDE patients presented differences in several CBC parameters, differences that were clearly pronounced and/or significant in concurrence with suicide attempts (SA). Red and white blood cell lineage parameters were affected, suggesting general haematopoietic modulation or imbalance. We observed distinct haematological parameter changes in women versus men, with men presenting milder alterations than women. Interestingly, we found that the List of Threatening Experiences (LTE) score, but not the Childhood Trauma Questionnaire (CTQ), was associated with the haematopoietic alterations observed exclusively in women and, more importantly, served as a parameter to stratify female MDE patients based on concurrence or non-concurrence with SA. In conclusion, grades of haematopoietic modulation in MDE patients are associated with absence or presence of SA. Haematopoietic manifestations differ between men and women and, in the latter, are markedly influenced by late, and not early, traumatic events.