Gender sensitivity of the COVID-19 mental health research in Europe: a scoping review.

BACKGROUND: The integration of sex and gender aspects into the research process has been recognized as crucial to the generation of valid data. During the coronavirus pandemic, a great deal of research addressed the mental state of hospital staff, as they constituted a population at risk for infection and distress. However, it is still unknown how the gender dimension was included. We aimed to appraise and measure qualitatively the extent of gender sensitivity. METHODS: In this scoping review, we searched MEDLINE, EMBASE, CINAHL PsycINFO and Social Sciences Citation Index (SSCI) from database inception to November 11, 2021. All quantitative studies with primary data published in English, German, or Spanish and based in the European Union were selected. Included studies had to have assessed the mental health of hospital staff using validated psychometric scales for depression, anxiety, PTSD symptoms, distress, suicidal behavior, insomnia, substance abuse or aggressive behavior. Two independent reviewers applied eligibility criteria to each title/abstract reviewed, to the full text of the article, and performed the data extraction. A gender sensitivity assessment tool was developed and validated, consisting of 18 items followed by a final qualitative assessment. Two independent reviewers assessed the gender dimension of each included article. RESULTS: Three thousand one hundred twelve studies were identified, of which 72 were included in the analysis. The most common design was cross-sectional (75.0%) and most of them were conducted in Italy (31.9%). Among the results, only one study assessed suicidal behaviors and none substance abuse disorders or aggressive behaviors. Sex and gender were used erroneously in 83.3% of the studies, and only one study described how the gender of the participants was determined. Most articles (71.8%) did not include sex/gender in the literature review and did not discuss sex/gender-related findings with a gender theoretical background (86.1%). In the analysis, 37.5% provided sex/gender disaggregated data, but only 3 studies performed advanced modeling statistics, such as interaction analysis. In the overall assessment, 3 papers were rated as good in terms of gender sensitivity, and the rest as fair (16.7%) and poor (79.2%). Three papers were identified in which gender stereotypes were present in explaining the results. None of the papers analyzed the results of non-binary individuals. CONCLUSIONS: Studies on the mental health of hospital staff during the pandemic did not adequately integrate the gender dimension, despite the institutional commitment of the European Union and the gendered effect of the pandemic. In the development of future mental health interventions for this population, the use and generalizability of current evidence should be done cautiously.

Psychosis and substance abuse increase the COVID-19 mortality risk.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders. METHODS: We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in the three territories of the Basque Country. COVID-19 cases were defined as individuals who had tested positive on a reverse transcription-polymerase chain reaction (PCR) test. Univariate and multivariate logistic regression models and multilevel analyses with generalized estimated equations were used to determine factors associated with COVID-19-related mortality and hospital admission. RESULTS: The COVID-19 mortality rate was increased for patients with psychotic disorders [odds ratio (OR) adjusted: 1.45, 95% confidence interval (CI) (1.09-1.94), p = 0.0114] and patients with substance abuse [OR adjusted: 1.88, 95% CI (1.13-3.14, p < 0.0152)]. The mortality rate was lower for patients with affective disorders [OR adjusted: 0.80, 95% CI (0.61-0.99), p = 0.0407]. Hospital admission rates due to COVID-19 were higher in psychosis [OR adjusted: 2.90, 95% CI (2.36-3.56), p < 0.0001] and anxiety disorder groups [OR adjusted: 1.54, 95% CI (1.37-1.72), p < 0.0001]. Among admitted patients, COVID-19 mortality rate was decreased for those with affective disorders rate [OR adjusted: 0.72, 95% CI (0.55-0.95), p = 0.0194]. CONCLUSIONS: COVID-19-related mortality and hospitalizations rates were higher for patients with a pre-existing psychotic disorder.

Gender differences in the management of acute psychiatric episodes in the emergency department: a cross-sectional analysis of the 2017-2019 triennium.

There is growing evidence that gender is an important determinant of mental health and well-being. In this sense, both biological and socio-economic factors play a key role in how people experience psychological disturbances. This study examine whether there were sex- and gender-based differences in the management of psychiatric disorders in the emergency department (ED). A cross-sectional retrospective study was conducted in the ED over the 2017-2019 period. Sex was codified as female/male and socio-economic deprivation index was compiled to address the impact of social determinants. Episodes were reclassified according to four major clusters. Psychotropic drug prescription was categorized according to the ATC classification. Poisson regression models, adjusted for age and socioeconomic status, were used. A total of 9789 episodes (53.9% females) of individuals who required an acute-related psychiatric intervention were retrieved. Age distribution and socioeconomic quintiles revealed gender differences. Anxiety-related consultations accounted for up to 50% of all episodes. Female gender was found to be overrepresented in anxiety and stress-related disorders, mood disorders, and personality disorders. In contrast, Males accounted for 70% of all psychoactive substance use disorders. Considering main clinical syndromic clusters, analysis showed that female patients were more likely to be prescribed with anxiolytic treatment in ED treatment than men in the categories of "Common mental disorders" (PR = 1.122 [1.014-1.242; p = 0.025), "Severe Mental Disorders" (PR = 1.217[1.054-1.406] p = 0.007) and "Personality disorders" (PR = 1.398 (1.038 - 1.884); p = 0.028). This study highlights the relevance of considering sex and gender as potential determinants in both the clinical presentation and management of psychiatric emergencies.

Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its most prevalent manifestation is neuropsychiatric SLE (NP-SLE), which is characterized by increased involvement of the nervous system, with relevant symptoms, such as marked cognitive deficits, which are directly involved in subsequent functional disability. The objective of this study is to identify and compare the profile of cognitive deficits in patients with NP-SLE and patients with non-neuropsychiatric SLE (nonNP-SLE) by means of a systematic review and meta-analysis. METHODS: We performed a systematic literature search based on the key words "cogn* OR neurocogn* AND lupus AND neuropsychiatry*" and included articles published between April 1999 and December 2016. A total of 244 articles were retrieved. We excluded reviews and meta-analyses, experiments not performed in humans, and single case reports. We included studies that used standardized cognitive measures and had included at least the subgroups NP-SLE and non NP-SLE. RESULTS: The meta-analysis was finally based on six studies, and 10 neuropsychological variables were examined. Significant differences were observed between the groups for six variables. In the remaining four variables, we observed marked heterogeneity between the groups or a low number of studies. CONCLUSIONS: The data obtained indicate greater cognitive impairment among NP-SLE patients than among nonNP-SLE patients, at least for the cognitive domains of visuomotor coordination, attention, executive function, visual learning and memory, and phonetic fluency. The identification and definition of cognitive deficits in SLE patients is necessary to develop adequate cognitive remediation programs to improve functional outcomes. (JINS, 2018, 24, 629-639).

Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional Assessment.

BACKGROUND: Studies on therapeutic drug monitoring (TDM) of second-generation antipsychotics (SGAs) have provided conflicting results regarding the association between dose, plasma concentrations, and drug effect and have focused rather on analyzing how individual drugs work. No study has attempted to process data from different SGAs globally to offer a panoramic view of the utility of TDM in clinical practice, and data on patients with first-episode psychosis (FEP) are lacking. This study aimed to assess the relationship between dose, plasma concentrations, and drug effect in a sample of patients with FEP, regardless of the SGA prescribed. METHODS: Data from 64 compliant patients treated with the same SGA during a 2-month follow-up were recorded. Clinical symptoms were assessed using the Positive and Negative Symptoms Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg für Kliniske Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents, and patients were classified into 3 different ranges according to their plasma concentrations (subtherapeutic, therapeutic, and supratherapeutic). RESULTS: Plasma concentration ranges were proportionally related to dose. Patients with supratherapeutic plasma concentrations were treated with doses significantly higher than those with subtherapeutic concentrations. Dose and plasma concentrations were not associated with early drug effect. CONCLUSIONS: TDM seems unable to accurately estimate the early effects of SGAs in FEP. Ours is the first study to categorize plasma concentrations of SGAs into ranges for joint processing of data from a larger number of patients.

A Pilot Study of the Usefulness of a Single Olanzapine Plasma Concentration as an Indicator of Early Drug Effect in a Small Sample of First-Episode Psychosis Patients.

PURPOSE/BACKGROUND: Studies analyzing concentration-effect relationships in second-generation antipsychotics have reported contradictory results in chronic schizophrenia. No data are available for the early stages of the disease. The present study aims to evaluate the association between a single olanzapine plasma concentration, clinical response, and severity of adverse effects in first-episode psychosis (FEP); to test the utility of various plasma breakpoints as markers of early response to treatment; and to identify variables affecting olanzapine concentrations. METHODS: Data from 23 compliant FEP patients receiving olanzapine monotherapy (5-30 mg/d) were evaluated 2 months after beginning treatment. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg for Kliniske Undersøgelser scale. Plasma samples were drawn at 11 (SD, 1) hours after dosing and analyzed with high-performance liquid chromatography/tandem mass spectrometry. FINDINGS: Consistent with findings on chronic disease, dose, age, sex, weight, and cigarettes/day accounted for some of the variability in olanzapine concentrations. While no relationship was found between olanzapine concentrations and adverse effects or improvement of depressive symptoms, response of psychotic symptoms was associated with concentrations between 22.56 and 77.92 ng/mL. Plasma breakpoints did not show sufficiently high specificity, resulting in a large number of false-positive results. IMPLICATIONS: Although olanzapine concentrations do not seem to be reliable indicators of early drug effect in FEP, they may still prove useful for detecting noncompliance, as well as pharmacokinetically relevant comorbidities or genetic particularities in drug metabolism.

Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus.

Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery-Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders.

Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Results: Across 11 head-to-head RCTs (n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99). Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. Trial registration: CRD42023407120 (PROSPERO).

OBJECTIVE: We aimed to uncover whether LAIs or regular antipsychotic pills demonstrate better outcomes over the medium and long term for individuals in the early stages of schizophrenia. METHOD: We scrutinized several studies comparing LAIs to regular pills in treating early-stage schizophrenia. Employing a combined analysis, we assessed factors such as preventing relapses and hospitalizations, as well as patient treatment adherence. DESIGN: We combined different study results in one unique analysis. We delved into whether LAIs surpassed regular pills in preventing relapses and hospitalizations and in patient treatment adherence. RESULTS: In our study of 11 trials involving over 2000 participants, we observed that LAIs and regular antipsychotic pills were generally comparable regarding preventing relapses, hospitalizations, and treatment adherence. However, on closer inspection, LAIs appeared slightly more effective for specific groups in the early stages of schizophrenia. CONCLUSION: While LAIs and regular antipsychotic pills showed similar results for most individuals in the early stages of schizophrenia, our findings hint at the possibility that LAIs might have a slight edge for certain groups. Nevertheless, we emphasize the need for more high-quality studies to gain a clearer understanding. REGISTRATION: This study is registered under CRD42023407120 (PROSPERO).

Comparing long-acting injections and pills for early schizophrenia: a study review and combined analysis Background: We explored whether antipsychotics long-acting injections (LAIs) might outperform regular antipsychotics pills for people dealing with early-stage conditions like schizophrenia. While LAIs have clear benefits for those with long-term challenges, their effectiveness for those just starting to grapple with these issues is less certain.

Clinical Management and Assessment of the Early Stages of Psychosis: A Multidimensional Approach.

Early intervention in psychosis has emerged as an integrated clinical and research strategy for the comprehensive care of people presenting with a first psychotic episode (FEP). In this sense, a multidisciplinary approach is essential for early detection and assessment of preliminary stages of the illness. The main objectives of early intervention programs include the implementation of specialized interventions aimed at promoting functional recovery and improving quality of life. In this chapter, we will describe the main advantages of specialized early intervention programs in psychosis. We will also describe the main aspects of assessment that need to be considered when approaching an FEP.

Violence in first-episode psychosis: evidence from an early intervention in psychosis programme.

BACKGROUND: Psychotic disorders are frequently associated with a public perception of dangerousness and belligerence. This situation has contributed to the social stigmatisation of people with severe mental illness and the resulting discrimination that this scenario entails. Despite efforts to demystify such disorders, the association between violent behaviour and psychosis remains unclear. AIMS: To explore the incidence of the main types of violent offences in a cohort of patients presenting with first-episode psychosis (FEP). METHOD: Participants were recruited from the First Episode Psychosis Intervention Program (CRUPEP) cohort between 2009 and 2016. The main clinical variables were collected, including medical-forensic records of participants registered at the Basque Institute of Forensic Medicine (BIFM), to identify any violent acts in which participants were involved, either as victims or as offenders. RESULTS: Overall, 79.5% (n = 182) of the participants had no record of violent crime or offence recorded in the BIFM. Annual crime rates for the 2009-2016 period show a decreasing trend in both the general population (IRR = 0.981, 95% CI 0.978-0.983, P < 0.001) and in the FEP group (IRR = 0.019, 95% CI 0.012-0.028, P < 0.001); this pattern is more pronounced in the FEP group. Victimisation accounted for the vast majority of reported incidents; nevertheless, participants who had committed violent offences were mostly involved in intrafamily violence. CONCLUSIONS: Individuals with FEP were not involved in a higher number of crimes than the general population. The types of violent acts committed by people with FEP were heterogeneous, with extreme violence being particularly uncommon.

Neuropsychological and Functional Assessment of Cognitive Impairments in Schizophrenia.

Cognitive deficits are a central feature of psychotic disorders. Their impact and relevance for clinical prognosis and functional recovery, together with their usefulness in the development of novel therapeutic targets, have emphasized the role of cognition in the diagnosis and therapeutic management of schizophrenia. Here we describe the main aspects to consider before, during, and after the neuropsychological assessment of main cognitive domains affected in schizophrenia, from a research perspective toward clinical practice.

First-episode psychosis intervention programme versus standard care for the clinical management of early phases of psychosis: cost analysis.

BACKGROUND: Early intervention programmes (EIPs) in psychosis have gained attention as specialised interventions to improve health-related and societal impacts for people with psychotic disorders. Previous studies have presented evidence in favour of EIPs over the first year of intervention, despite none considering the critical period before psychosis onset (5 years). AIMS: To compare the associated costs of the First Episode Psychosis Intervention Program (CRUPEP) and treatment as usual (TAU) in a real-world cohort in a non-specialised psychiatric community setting. METHOD: Direct and indirect mental health-related costs were calculated over 1 year and up to 7 years. Healthcare and societal costs were calculated from economic data related to the consumption of all healthcare resources, including emergency department attendances, hospital admissions, psychotropic medication prescriptions and societal costs. RESULTS: From a healthcare perspective, the intervention (CRUPEP) group initially showed a marginally higher cost per patient than the TAU group (€7621 TAU group v. €11 904 CRUPEP group) over the first year of follow-up. However, this difference was reversed between the groups on considering the entire follow-up, with the TAU group showing considerably higher associated costs per patient (€77 026 TAU v. €25 247 CRUPEP). CONCLUSIONS: The EIP (CRUPEP) showed clinical benefits and minimised the direct and indirect health-related costs of the management of psychosis. Although the CRUPEP intervention initially reported increased costs over 1 year, TAU surpassed the global costs over the entire follow-up.

Isolation and Differentiation of Neurons and Glial Cells from Olfactory Epithelium in Living Subjects.

The study of psychiatric and neurological diseases requires the substrate in which the disorders occur, that is, the nervous tissue. Currently, several types of human bio-specimens are being used for research, including postmortem brains, cerebrospinal fluid, induced pluripotent stem (iPS) cells, and induced neuronal (iN) cells. However, these samples are far from providing a useful predictive, diagnostic, or prognostic biomarker. The olfactory epithelium is a region close to the brain that has received increased interest as a research tool for the study of brain mechanisms in complex neuropsychiatric and neurological diseases. The olfactory sensory neurons are replaced by neurogenesis throughout adult life from stem cells on the basement membrane. These stem cells are multipotent and can be propagated in neurospheres, proliferated in vitro and differentiated into multiple cell types including neurons and glia. For all these reasons, olfactory epithelium provides a unique resource for investigating neuronal molecular markers of neuropsychiatric and neurological diseases. Here, we describe the isolation and culture of human differentiated neurons and glial cells from olfactory epithelium of living subjects by an easy and non-invasive exfoliation method that may serve as a useful tool for the research in brain diseases.

Negative symptoms and sex differences in first episode schizophrenia: What's their role in the functional outcome? A longitudinal study.

INTRODUCTION: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. MATERIAL AND METHODS: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. RESULTS: Females showed fewer NS (p=0.031; Cohen's d=-0.312), especially those related to EXP (p=0.024; Cohen's d=-0.326) rather than MAP (p=0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R2=0.494; p<0.001), while only higher deficits in MAP predicted worse functioning in males (R2=0.088; p=0.012). CONCLUSIONS: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes.

Similarities in early course among men and women with a first episode of schizophrenia and schizophreniform disorder.

The aims of this study were to analyze the presence of gender differences in the phenotypic expression of schizophrenia at the onset of illness and to explore whether these differences determine clinical and functional outcome 2 years after the initiation of treatment. Data from 231 first-episode-psychosis non-substance-dependent patients (156 men and 75 women) participating in a large-scale naturalistic open-label trial with risperidone were recorded at inclusion and months 1, 6, 12, and 24. Men presented a significant earlier age of onset (24.89 years vs. 29.01 years in women), poorer premorbid functioning, and a higher presence of prodromal and baseline negative symptoms. Women were more frequently married or lived with their partner and children and more frequently presented acute stress during the year previous to onset than men. No other significant clinical or functional differences were detected at baseline. The mean dose of antipsychotic treatment was similar for both genders during the study, and no significant differences in UKU scores were found. The number of hospitalizations was similar between groups, and adherence was more frequent among women. At the 2-year follow-up, both groups obtained significant improvements in outcome measures: PANSS, CGI severity, and GAF scores. Significant gender * time interactions were detected for negative and general PANSS subscales, with the improvement being more pronounced for men. However, no differences were detected for the mean scores obtained during the study in any outcome measure, and the final profile was similar for men and women. Our results suggest that although the initial presentation of schizophrenia can differ according to gender, these differences are not sufficient enough to determine differentiated outcome 2 years after the initiation of treatment in non-substance-dependent patients. The influence of gender on the early course of schizophrenia does not seem to be clinically or functionally decisive in this population.

Relation between EEG resting-state power and modulation of P300 task-related activity in theta band in schizophrenia.

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.

Cognitive performance and smoking in first-episode psychosis: the self-medication hypothesis.

The self-medication hypothesis attempts to explain the extraordinary high levels of cigarette smoking in schizophrenia; patients may smoke in an attempt to reduce their cognitive deficits, symptoms, or the side effects of antipsychotics. In a previous report, we detected beneficial performance in attention and working memory in patients with first-episode psychosis who smoked compared to non-smoking patients soon after stabilization. In the present study, we examine differences in the course of those deficits 12 months after the initiation of antipsychotic treatment. We also explore the association between smoking and symptoms and side effects of medication. Neuropsychological assessments were performed at baseline, month 6 and month 12 using a computerized battery that included measures of sustained attention (Continuous Performance Test CPT-O), selective attention (Stroop interference task) and working memory (CPT-XO). Patients met the criterion of fitting in the same smoking category throughout the study: non-smoker (n = 15; 0 cigarettes/day) and smoker (n = 26; >15 cigarettes/day). The non-smoking patients showed significant cognitive improvements, whereas smoking patients lost their superior baseline performance, which was probably obtained through nicotinic stimulation, at the 6- and 12-month assessments due to a static course of deficits. Smokers did not obtain any cognitive benefit after instauration of treatment and worsen their symptoms over the first year. These results suggest that smoking may constitute a marker of a more severe illness. Smoking was not associated with fewer extrapyramidal side effects. Smoking might improve attention and working memory to a similarly modest extent as atypical antipsychotics and could reflect an effort to ameliorate these cognitive dysfunctions previous to treatment instauration.

Long-acting injectable aripiprazole in pregnant women with schizophrenia: a case-series report.

Antipsychotic long-acting formulations (LAI-AP) have emerged as a new therapeutic choice to treat patients presenting a severe mental disorder. Despite that, to date, there is a lack of safety data and studies regarding the use of LAI-AP formulations in pregnant women. Here we present the first six-case series of pregnant women with schizophrenia treated with aripiprazole-LAI reported in the literature. All patients remained psychopathologically stable through pregnancy and the postpartum period, and all of them were in treatment with aripiprazole-LAI. To date, all infants remain healthy with normal developmental milestones, without the presence of congenital malformations or adverse effects. Lack of information on safety data regarding the use of new antipsychotic formulations remains important in treating women with mental illness who desire to become pregnant. Further studies in this clinical population with a larger number of patients included remains necessary.

Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms.

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (α7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia. Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus α7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence. Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of α7 nAChR agonists for negative symptoms [standardized mean difference -0.28, 95% CI (-0.56 to -0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system. Conclusions: Current evidence is too weak to consider α7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.

Characterization of dopamine D2 receptor coupling to G proteins in postmortem brain of subjects with schizophrenia.

BACKGROUND: Alterations of dopamine D1 (D1R) and D2 receptor (D2R) are proposed in schizophrenia but brain neuroimaging and postmortem studies have shown controversial results in relation to D1R and D2R density. Besides, scarce information on the functionality of brain D1R and D2R is available. The present study characterized G-protein activation by D1R and D2R agonists in postmortem human brain. Furthermore, D2R functional status was compared between schizophrenia and control subjects. METHODS: G-protein receptor coupling was assessed in control caudate nucleus and frontal cortex by [35S]GTPγS-binding stimulation induced by increasing concentrations (10-10-10-3 M) of dopamine, and the selective dopaminergic agonists SKF38393 (D1R) and NPA (D2R). Concentration-response curves to NPA stimulation of [35S]GTPγS binding were analyzed in antipsychotic-free (n = 10) and antipsychotic-treated (n = 7) schizophrenia subjects and matched controls (n = 17). RESULTS: In caudate, [35S]GTPγS-binding responses to agonists were compatible with the existence of functional D2R. In contrast, stimulations in cortex showed responses that did not correspond to D1R or D2R. [35S]GTPγS-binding activation by NPA in caudate displayed biphasic curves with similar profile in schizophrenia (EC50H = 7.94 nM; EC50L = 7.08 µM) and control (EC50H = 7.24 nM; EC50L = 15.14 µM) subjects. The presence or absence of antipsychotic medication did not influence the pharmacological parameters. CONCLUSIONS: Feasibility of functional evaluation of dopamine receptors in postmortem human brain by conventional [35S]GTPγS-binding assays appears to be restricted to signalling through inhibitory Gi/o proteins. These findings provide functional information about brain D2R status in subjects with schizophrenia and do not support the existence of D2R supersensitive in this mental disorder.