Inflammatory blood cells and ratios at remission for psychosis relapse prediction: A three-year follow-up of a cohort of first episodes of schizophrenia.

BACKGROUND: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. METHODS: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. RESULTS: Monocyte counts (OR = 1.91; 95 % CI = 1.07-3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01-1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03-2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01-1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. CONCLUSION: This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period.

Impact of Delusions and Hallucinations on Clinical Insight Dimensions in Schizophrenia Spectrum Disorders.

INTRODUCTION: Insight in psychosis has been conceptualized as a continuous, dynamic, and multidimensional phenomenon. This study aims to determine the impact of delusions and hallucinations in different dimensions of clinical insight in schizophrenia spectrum disorders. METHODS: Cross-sectional multicenter study including 516 patients (336 men) diagnosed with schizophrenia spectrum disorders. Based on dichotomized scores of Positive and Negative Syndrome Scale (PANSS) items P1 (delusions) and P3 (hallucinations), patients were assigned to four groups according to current clear presence of delusions (scores 4 or above 4 in PANSS item P1) and/or hallucinations (scores 4 or above 4 in PANNS item P3). Insight was assessed using the three main dimensions of the Scale of Unawareness of Mental Disorder (SUMD). RESULTS: Around 40% of patients showed unawareness of illness; 30% unawareness of the need for treatment; and 45% unawareness of the social consequences of the disorder. Patients with current clear presence of delusions had higher overall lack of awareness, regardless of current clear presence of hallucinations. Similarly, the clear presence of delusions showed a greater predictive value on insight than the presence of hallucinations, although the implication of both in the prediction was modest. CONCLUSIONS: Our results confirm that lack of insight is highly prevalent in schizophrenia spectrum disorders, particularly when patients experience delusions. This study adds insight-related data to the growing symptom-based research, where specific types of psychotic experiences such as hallucinations and delusions could form different psychopathological patterns, linking the phenomenology of delusions to a lack of clinical insight.

The influence of gender in cognitive insight and cognitive bias in people with first-episode psychosis: an uncontrolled exploratory analysis.

PURPOSE: Previous studies have investigated the role of gender in clinical symptoms, social functioning, and neuropsychological performance in people with first-episode psychosis (FEP). However, the evidence of gender differences for metacognition in subjects with FEP is still limited and controversial. The aim of the present study was to explore gender differences in cognitive insight and cognitive biases in this population. METHODS: Cross-sectional study was carried out in a sample of 104 patients with FEP (35 females and 69 males) recruited from mental health services. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive insight with the Beck Cognitive Insight Scale, and cognitive bias by the Cognitive Biases Questionnaire for Psychosis. The assessment also included clinical and sociodemographic characteristics. RESULTS: After controlling for potential confounders (level of education, marital status, and duration of psychotic illness) analysis of covariance revealed that males presented greater self-reflectiveness (p = 0.004) when compared to females. However, no significant differences were found in self-certainty and composite index of the cognitive insight scale, as in the cognitive biases assessed. CONCLUSIONS: Gender was an independent influence factor for self-reflectiveness, being better for males. Self-reflectiveness, if shown to be relatively lacking in women, could contribute to the design of more gender-sensitive and effective psychotherapeutic treatments, as being able to self-reflect predicts to better treatment response in psychosis.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations.

BACKGROUND: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

Identifying risk factors for predominant negative symptoms from early stages in schizophrenia: A longitudinal and sex-specific study in first-episode schizophrenia patients.

BACKGROUND: People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS. METHODS: In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up. RESULTS: In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607). CONCLUSIONS: A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology.

Perspective of patients with first-episode psychosis, their relatives, and mental health professionals on the design and usability of an app in clinical practice.

AIM: Therapeutic non-compliance remains the main difficulty for people with psychotic disorders, standing around 50% in people with schizophrenia. Lack of treatment adherence, either partial or total, to medication has economic and clinical consequences. E-health technologies may be a promising therapeutic tool to improve adherence, with the subsequent reduction in clinical and economic burden. Our aims were to know the preferences on how technologies in mental health treatment should be for use in clinical practice, and to learn about the opinion and preferences on the use of technologies in mental health treatment from the perspectives of patients with FEP, their relatives, and mental health professionals. METHODS: Forty-one patients with a diagnosis of first-episode psychosis (FEP), 18 relatives and 49 mental health professionals were included in the study. They completed an online survey related to the use, availability and user-skill of online platforms and apps created by a group of experts in psychosis and in the use of technologies. Data were summarized in frequencies, percentages, and means, and Chi-square tests were used to calculate differences between-groups. RESULTS: An app directed to people with psychosis would be well received by users if it contains psychoeducational material, offers reminders for scheduled visits and treatment and allows online consultations. CONCLUSIONS: Co-creating an app with users, their families and mental health professionals allows incorporating their preferences to increase its use, improve outpatient care and creating an app that is viable in clinical practice.

The polygenic basis of relapse after a first episode of schizophrenia.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.

Development and validation of a short version of the questionnaire of stressful life events (QSLE).

Stressful life events (SLE) tend to occur before the onset of psychosis, this highlights the importance of its detection and evaluation in these patients. The need to have instruments that assess SLE easily and quickly underpins the objective of this study, which is to validate a short version of the questionnaire of stressful life events (QSLE). 124 patients with first-episode psychosis and 218 healthy controls aged between 11 and 52 years were recruited. The QSLE scale underwent discrimination analysis, which revealed 18 items had good SLEs discriminability between the two samples. These 18 items were then used to create the shorter QSLE-SV. The QSLE-SV showed good internal consistency (Cronbach's alpha = 0.749). An AUC of 0.830 was observed, suggesting that the predictor was good. Using 2 as the cut-off score to predict an individual as a patient would yield a sensitivity of 91.1% and a specificity of 51.6%, and using a cut-off point of 3, the sensitivity was 77.4% and the specificity was 72.5%. QSLE-SV displayed satisfactory psychometric properties in a Spanish population. The QSLE-SV allows for investigating childhood, adolescent and adult life events by measuring current stress and age on a continuous scale in a quick and easy way.

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study.

BACKGROUND: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. OBJECTIVE: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. METHODS: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. RESULTS: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. CONCLUSIONS: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-021346.

Association of perceived social support with sociodemographic, clinical, and psychosocial variables in patients with first-episode psychosis.

Patients with first-episode psychosis (FEP) report deficits in social support (SS) and diminished and less satisfactory social networks than healthy controls (HC). These SS difficulties are linked with symptomatology. The study objectives were to: (a) compare perceived SS between patients with FEP and HC; (b) study sex differences regarding perceived SS in patients with FEP and HC; and (c) explore which sociodemographic, clinical and psychosocial variables are related to perceived SS in the onset of FEP. A total of 146 participants were included: 76 patients with FEP (24 females, 52 males) and 70 HC (20 females, 50 males). Perceived SS was assessed with the DUKE-UNK instrument, which is divided into two subscales: confidant support (CS) and affective support (AS). Significant differences regarding perceived SS were observed between the samples. No sex differences were found concerning perceived SS in each group. For the group with FEP, more years of education, less anxiety/depressive symptoms and better functioning were the most relevant variables for more overall perceived SS and perceived CS. Also, less suicidal risk was the only important indicator for more perceived AS. Interventions in perceived SS could contribute to a good evolution of FEP.

Estrategias de afrontamiento durante el confinamiento por COVID-19 en pacientes con primer episodio psicótico: el impacto en su vida diaria / Coping strategies during covid-19 lockdown in patients with first-episode psychosis: the impact on their daily life

Introducción: El confinamiento por la enfermedad del coronavirus 2019 (COVID-19) interrumpió la vida de todo el mundo en marzo de 2020. El confinamiento obligatorio duró dos meses, lo que tuvo un impacto en la salud mental de las personas. Sin embargo, se desconoce en gran medida cómo afectó a quienes ya luchaban con problemas de salud mental. Métodos: Se recopiló información de 18 pacientes con primer episodio psicótico (PEP) mediante una encuesta en línea. La encuesta tenía preguntas sobre COVID-19, el impacto del confinamiento en la vida diaria y las estrategias de afrontamiento utilizadas durante el confinamiento entre marzo y abril de 2020 en España. Resultados: Algunas estrategias de afrontamiento se asociaron con diferentes actividades de la vida diaria: normalizar la situación, buscar ayuda de amigos o familiares y buscar ayuda de profesionales en situaciones estresantes, leer fuentes de información y autoayuda para enfrentar el estrés, enfocarse en las emociones que generan estrés, intentar centrarse en problemas concretos y buscar soluciones, y aceptar la situación con resignación. Conclusiones: Como conclusión, los resultados sugieren que no todas las estrategias de afrontamiento impactaron de la misma manera en la vida diaria de los/las pacientes con PEP durante el confinamiento por COVID-19.(AU)

Introduction: Lockdown for 2019 coronavirus disease (COVID-19) disrupted life worldwide from March 2020. Mandatory lockdown lasted two months, which had an impact on people’s mental health. However, how it affected those who already struggled with mental health problems is largely unknown. Methods: We collected information from 18 patients with first-episode psychosis (FEP) through an online survey. The survey contained questions regarding COVID-19, impact of confinement on daily life, and coping strategies during lockdown between March and April 2020 in Spain. Results: Some coping strategies were associated with different daily life activities: normalizing the situation, seeking help from friends or family, and seeking help from professionals in stressful situations, reading information sources and self-help to cope with stress, focusing on the emotions that generate stress, trying to focus on specific problems and seek solutions, and accepting the situation with resignation. Discussion: As a conclusion, results suggest that not all coping strategies impacted in the same way in daily life of patients with FEP during COVID-19 lockdown.(AU)

The relevance of processing speed in the functioning of people with first-episode psychosis.

Deficits in functioning affect people with first-episode psychosis. Deficits in cognitive performance are common in such individuals and appear to be related to functioning. The present study examined the relationship between the domains of cognitive performance and personal and social functioning, as well as evaluating which cognitive domains are the most closely related to personal and social functioning and whether they explain variations once other clinical and sociodemographic aspects are accounted for. Ninety-four people with first-episode psychosis participated in the study; they were assessed with the MATRICS battery. Symptoms were evaluated with the Emsley factors of the positive and negative syndrome scale. Cannabis use, duration of untreated psychosis, suicide risk, perceived stress, antipsychotic doses, and premorbid intelligence quotient was accounted for. Processing speed, attention/vigilance, working memory, visual learning, reasoning and problem solving correlated to personal and social functioning. Processing speed emerged as the strongest predictor of social and personal functioning and underscores the importance of targeting this domain in treatment. Moreover, suicide risk and excited symptoms were also significant variables in functioning. Early intervention, focusing on improvement of processing speed, may be crucial to the improvement of functioning in first-episode psychosis. The relationship of this cognitive domain with functioning in first-episode psychosis should be studied further.

Impact of traumatic life events on clinical variables of individuals with first-episode psychosis and healthy controls.

BACKGROUND: Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). AIMS: To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. METHODS: Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. RESULTS: We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. CONCLUSIONS: The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.

Relapse, cognitive reserve, and their relationship with cognition in first episode schizophrenia: a 3-year follow-up study.

Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness.

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.

Sex differences in symptomatology in people with schizophrenia and other psychotic disorders: protocol for a systematic review and pairwise meta-analysis of observational studies.

SUMMARY: Sex differences in symptomatology in people with psychosis have been studied extensively in recent decades. Although studies have pointed to such differences, to date there is no review that has performed a systematic search and quantitative synthesis. In this paper, we describe the protocol for a pairwise meta-analysis comparing a range of symptom outcome measures between men and women diagnosed with a psychotic spectrum disorder at different stages of the disorder (PROSPERO registration number CRD42021264942). In August 2021 we conducted systematic searches of PsychInfo, PubMed, Web of Science, Scopus and Dialnet to identify observational studies that report data on symptoms for males and females separately. Two independent reviewers will conduct literature searches, select studies, extract data, assess the risk of bias and assess outcome quality. To assess the effect size of all outcome measures, we will conduct pairwise meta-analysis using random-effects models. The quality of studies will be evaluated using a National Heart, Lung and Blood Institute's quality assessment tool and the confidence in the results will be evaluated using the GRADE tool. Meta-regression and sensitivity analyses will be conducted to assess the robustness of the findings. No ethical problems are foreseen. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.

Relapse of first-episode schizophrenia patients and neurocognitive impairment: The role of dopaminergic and anticholinergic burden.

BACKGROUND: The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up. METHODS: Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, after >2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions. RESULTS: Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden. CONCLUSIONS: The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.

Epigenetic clocks in relapse after a first episode of schizophrenia.

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages.

Emotional abuse and perceived stress: The most relevant factors in suicide behavior in first-episode psychosis patients.

People with a mental disorder have a higher risk of suicidal behavior. Little research has examined the role of childhood trauma in suicide behavior, and even fewer studies have assessed the specific relevance of subtypes of childhood trauma and suicidal behavior in first-episode psychosis (FEP). The aims of the present study were: 1) to compare suicide behavior between FEP and HC; 2) to study the relationship between the five types of ChT and suicide risk in FEP controlling for confounding sociodemographic, clinical, and psychosocial variables. 95 patients diagnosed with FEP and 92 healthy control (HC) were recruited as a part of the PROFEP study. ChT was evaluated using The Childhood Trauma Questionnaire-Short Form (CTQ) and suicide behavior through The Suicide Risk Scale of Plutchik (SRSP). Our results showed that patients with FEP presented more suicide behavior (ideation, attempt, and suicide risk) than HC. Emotional abuse was the most relevant type of ChT in suicide ideation and suicide risk. After controlling for other relevant variables, perceived stress seemed to play an important role in suicide ideations, suicide attempt, and suicide risk. The results highlight the importance of assessing and considering in the clinical practice ChT and the perceived stress.

Clinical and treatment predictors of relapse during a three-year follow-up of a cohort of first episodes of schizophrenia.

Relapses are frequent in the first years following a first episode of schizophrenia (FES), being associated with a higher risk of developing a chronic psychotic disorder, and poor clinical and functional outcomes. The identification and intervention over factors associated with relapses in these early phases are timely and relevant. In this study, 119 patients in remission after a FES were closely followed over three years. Participants came from the 2EPS Project, a coordinated, naturalistic, longitudinal study of 15 tertiary centers in Spain. Sociodemographic, clinical, treatment and substance abuse data were analyzed. 49.6% of the participants relapsed during the 3-years follow-up. None of the baseline demographic and clinical characteristics analyzed showed a statistically significant association with relapses. 22% of patients that finished the follow-up without relapsing were not taking any antipsychotic. The group that relapsed presented higher mean antipsychotics doses (381.93 vs. 242.29 mg of chlorpromazine equivalent/day, p = 0.028) and higher rates of antipsychotic polytherapy (28.6% vs. 13%, p < 0.001), benzodiazepines use (30.8% vs. 8.5%, p < 0.001), side effects reports (39.2% vs. 25%, p = 0.022), psychological treatment (51.8% vs. 33.9%, p = 0.03), and cannabis consumption (93.2% vs. 56.7%, p < 0.001). Clozapine use was notably higher in the group that reminded in remission (21.7% vs. 8.2%, p < 0.019). These findings may guide clinicians to detect subgroups of patients with higher risk to present a second episode of psychosis, focusing on measures to ensure an adequate treatment or facilitating cannabis use cessation. This study supports future research to identify relapse prevention strategies for patients in early phases of schizophrenia.