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.

Aprendizaje y memoria verbal: Comparación entre pacientes con trastorno por consumo de alcohol y trastorno de depresión mayor / Learning and verbal memory: A comparison between patients with alcohol use disorder and major depressive disorder

El daño cerebral relacionado con el consumo de alcohol se asocia a alteraciones de las funciones cognitivas, entre las que destacan memoria y aprendizaje verbal. El objetivo principal es evaluar memoria y aprendizaje verbal en una muestra de 111 pacientes con trastorno por consumo de alcohol (TCA) versus 78 con trastorno de depresión mayor (TDM) y 100 controles sanos. La evaluación incluyó variables sociodemográficas y clínicas, la Escala de Hamilton para la Depresión (HDRS) y el Test de Aprendizaje Verbal de California (CVLT). Se utilizó ANOVA de un factor para comparaciones entre los 3 grupos y ANCOVAS bidireccionales incluyendo diferentes covariables. El ANOVA de un factor muestra que los pacientes con TCA y TDM obtienen puntuaciones similares entre sí e inferiores a las del grupo control (p < 0,001), con excepción del CVLT Guiado (peores puntuaciones en TDM vs TCA, p < 0,001). Tras incluir como covariables la edad, sexo y los años de estudios completados, persisten las diferencias entre los grupos de TCA y TDM frente al grupo control (p ≤ 0,003) en todos los índices con excepción del CVLT Libre Inmediato y del CVLT Guiado (peor rendimiento en TDM vs TCA, p = 0,022 y p = 0,035, respectivamente). En el segundo ANCOVA, tras controlar por gravedad de la depresión, únicamente se detectan diferencias entre los pacientes con TCA y los controles sanos (p ≤ 0,007). Los pacientes con TCA presentan una importante alteración en aprendizaje y memoria verbal al compararlos con pacientes con TDM y con personas sanas. (AU)

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p <0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p <0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people. (AU)

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)

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.

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.

Early Impact of the COVID-19 Outbreak on Sleep in a Large Spanish Sample.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) forced Spain to implement unprecedented lockdown restriction. In this context, different factors could worsen sleep quality, but the impact of the pandemic and lockdown on sleep is still mostly unknown. In this cross-sectional study, we describe self-reported sleep disturbances in people without mental health disorders from a large Spanish sample (n = 15,070). METHODS: During the early phase of the lockdown (19-26 March), an online survey was launched using a snowball sampling method and included sociodemographic and clinical data along with the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). Two items of the IES were employed to assess sleep characteristics. Descriptive and bivariate analysis and logistic regression models were performed. RESULTS: Difficulty initiating or maintaining sleep were reported by 23.9% of the sample and was associated in the regression model with age (OR = 1.008, p = .003), female sex (OR = 1.344, p < .001), an income reduction >50% (OR = 1.248, p = .037), having one (OR = 1.208, p = .029) and two or more (OR = 1.299, p = .035) elderly dependents, drinking alcohol (OR = 1.129, p = .024), and a higher score on DASS-21 depression (OR = 1.148, p < .001), anxiety (OR = 1.218, p < .001), or stress (OR = 1.302, p < .001) subscales, whereas being able to enjoy free time (OR = 0.604, p < .001) and painting or listening to music (OR = 0.853, p = .012) were protective factors. Dreams related to COVID-19 were reported by 12.9% of the sample and were associated in the regression model with female sex (OR = 1.617, p < .001), being married (OR = 1.190, p = .015), self-employed (OR = 1.373, p = .032), or a civil servant (OR = 1.412, p = .010), having been tested for COVID-19 (OR = 1.583, p = .012), having infected family or friends (OR = 1.233, p = .001), reading news about coronavirus (OR = 1.139, p = .023), drinking alcohol (OR = 1.251, p < .001), and higher scores on DASS-21 depression (OR = 1.102, p < .001), anxiety (OR = 1.222, p < .001), or stress (OR = 1.213, p < .001) subscales, while protective factors were older age (OR = 0.983, p < .001) and being retired (OR = 0.625, p = .045). CONCLUSIONS: These findings could help clinicians and public health systems design and deliver tailored interventions, such as internet-delivered campaigns, to promote sleep quality in the general population.

Learning and verbal memory: A comparison between patients with alcohol use disorder and major depressive disorder. / Aprendizaje y memoria verbal: Comparación entre pacientes con trastorno por consumo de alcohol y trastorno de depresión mayor.

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p <0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p <0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.

El daño cerebral relacionado con el consumo de alcohol se asocia a alteraciones de las funciones cognitivas, entre las que destacan memoria y aprendizaje verbal. El objetivo principal es evaluar memoria y aprendizaje verbal en una muestra de 111 pacientes con trastorno por consumo de alcohol (TCA) versus 78 con trastorno de depresión mayor (TDM) y 100 controles sanos. La evaluación incluyó variables sociodemográficas y clínicas, la Escala de Hamilton para la Depresión (HDRS) y el Test de Aprendizaje Verbal de California (CVLT). Se utilizó ANOVA de un factor para comparaciones entre los 3 grupos y ANCOVAS bidireccionales incluyendo diferentes covariables. El ANOVA de un factor muestra que los pacientes con TCA y TDM obtienen puntuaciones similares entre sí e inferiores a las del grupo control (p < 0,001), con excepción del CVLT Guiado (peores puntuaciones en TDM vs TCA, p < 0,001). Tras incluir como covariables la edad, sexo y los años de estudios completados, persisten las diferencias entre los grupos de TCA y TDM frente al grupo control (p ≤ 0,003) en todos los índices con excepción del CVLT Libre Inmediato y del CVLT Guiado (peor rendimiento en TDM vs TCA, p = 0,022 y p = 0,035, respectivamente). En el segundo ANCOVA, tras controlar por gravedad de la depresión, únicamente se detectan diferencias entre los pacientes con TCA y los controles sanos (p ≤ 0,007). Los pacientes con TCA presentan una importante alteración en aprendizaje y memoria verbal al compararlos con pacientes con TDM y con personas sanas.

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.

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.

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.

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.

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.

COVID-19 lockdown in people with severe mental disorders in Spain: Do they have a specific psychological reaction compared with other mental disorders and healthy controls?

The COVID-19 pandemic and the lockdown restrictions could have adverse consequences for patients with severe mental disorders (SMD). Here, we aim to compare the early psychological impact (depression, anxiety, and stress responses, intrusive and avoidant thoughts, and coping strategies) on people with SMD (n = 125) compared with two control groups: common mental disorders (CMD, n = 250) and healthy controls (HC, n = 250). An anonymous online questionnaire using a snowball sampling method was conducted from March 19-26, 2020 and included sociodemographic and clinical data along with the DASS-21 and IES scales. We performed descriptive and bivariate analyses and multinomial and linear regression models. People with SMD had higher anxiety, stress, and depression responses than HC, but lower scores than CMD in all domains. Most people with SMD (87.2%) were able to enjoy free time, although control groups had higher percentages. After controlling for confounding factors, anxiety was the only significant psychological domain with lower scores in HC than people with SMD (OR = 0.721; 95% CI: 0.579-0.898). In the SMD group, higher anxiety was associated with being single (beta = 0.144), having COVID-19 symptoms (beta = 0.146), and a higher score on the stress subscale of DASS-21 (beta = 0.538); whereas being able to enjoy free time was a protective factor (beta = -0.244). Our results showed that patients with SMD reacted to the pandemic and the lockdown restrictions with higher anxiety levels than the general public, and suggesting this domain could be a criterion for early intervention strategies and closer follow-up.

Longitudinal effects of clozapine concentration and clozapine to N-desmethylclozapine ratio on cognition: A mediation model.

Previous cross-sectional studies have found clozapine to N-desmethylclozapine (CLZ:NDMC) ratio to be negatively correlated with cognition in clozapine-treated patients with schizophrenia. However, no work has examined the association between CLZ:NDMC ratio and cognition using a within-subjects design. Here, we investigate the longitudinal effects of changes in the clozapine load and the CLZ:NDMC ratio on cognition whilst controlling for a range of independent factors. We analyzed data from a cohort of seventeen clozapine-treated patients who have been repeatedly assessed with the Brief Assessment of Cognition for Schizophrenia (BACS). The Positive symptoms sub-score of the Clinical Global Impression for Schizophrenia (CGI-P) was used to assess severity of psychosis. Blood samples were collected to measure the plasmatic levels of clozapine (CLZ) and of N-desmethylclozapine, allowing calculation of the CLZ:NDMC ratio. Our analyses included bivariate and partial correlations, along with a mediation model analysis. We found that both plasmatic levels of CLZ and the CLZ:NDMC ratio were negatively correlated with cognitive performance, and that these associations were independent of changes in both daily clozapine dose and severity of psychotic symptoms. Mediation analyses further revealed the association between CLZ concentration and cognition to be partially mediated by changes in the CLZ:NDMC ratio. This is the first longitudinal analysis of the influence of CLZ concentration and CLZ:NDMC ratio on cognition. Our findings suggest that reduction of CLZ concentration and the CLZ:NDMC ratio might favorably affect cognition. Thus, the CLZ:NDMC ratio may represent a promising target for novel therapeutic strategies aiming to ameliorate cognitive impairment in clozapine-treated patients.

Predicting real-world functioning in outpatients with schizophrenia: Role of inflammation and psychopathology.

Several studies indicate that negative and cognitive symptoms are determining factors of functioning in patients with schizophrenia. However, they do not usually include biological aspects, such as inflammatory markers. The current prospective study aims to identify clinical and biological factors predicting real-world functioning, at baseline and at one-year follow-up, of outpatients in an early stage of schizophrenia. Sample consist of 73 clinically stable patients with schizophrenia, of which 57 completed the one-year follow-up. Accurate psychopathology, functioning, and cognitive assessments were performed at baseline and follow-up (Positive and Negative Syndrome, Brief Negative Symptom, Calgary Depression, Personal and Social Performance Scales, and MATRICS Cognitive Consensus Battery). Biological biomarkers including anthropometric data and blood parameters were collected. Pearson correlation and multiple regression analyses including potential confounding factors were performed. Negative symptoms (especially asociality and avolition), along with the inflammatory biomarker interleukin-2, are the most important determining factors of poor real-world functioning in early-stage schizophrenia. The previous functioning, along with baseline cognitive performance in attention and vigilance, predicts functioning at one-year follow-up in these patients. Strategies aimed at improving negative and cognitive symptoms, as well as modifying certain inflammatory pathways, should be the targets to achieve functional recovery in the first years of schizophrenia.